4th EDITION

the STROKE SOCIETY of the PHILIPPINES

Guidelines for the Prevention, Treatment and Rehabilitation of Brain Attack A Project of the Stroke Society of the Philippines

Front Panel Painting; “LIFE”

By: William T. Chua, M.D Director, Heart Institute

St. Luke’s Medical Center

Guidelines for the Prevention, Treatment and Rehabilitation of Brain Attack

STROKE: THINK GLOBALLY, ACT LOCALLY

Principles:

1. Stroke is a "brain attack"

… needing emergency management, including specific treatment

and secondary and tertiary prevention.

2. Stroke is an emergency

… where virtually no allowances for worsening is tolerated.

3. Stroke is treatable

… optimally, through proven, affordable, culturally acceptable and

ethical means.

4. Stroke is preventable

… in a manner that could be implemented across all levels of society.

The recommendations contained in this document are intended to merely guide practitioners in the prevention, treatment and rehabilitation of patients with stroke. In no way should these recommendations be regarded as absolute rules, since nuances and peculiarities in individual patients, situations or communities may entail differences in specific approaches. The recommendations should supplement, not replace, sound clinical judgments on a case-to-case basis.

TABLE OF CONTENTS

I. Message from the Founding President II. Message from the President III. Guidelines for the Primary and Secondary Prevention of Stroke

a. Preface to the Guidelines for the Primary and Secondary Prevention of Stroke

b. Hypertension c. Transient Ischemic Attack d. Diabetes Mellitus e. Atrial Fibrillation f. Acute Myocardial Infarction (With Left Ventricular Thrombus) and

Cardiomyopathy g. Valvular Heart Disease h. Carotid Stenosis i. Intracranial Stenosis j. Smoking k. Excessive Alcohol l. Peripheral Arterial Disease m. Physical Inactivity n. Obesity o. Diet

IV. Guidelines for Acute Stroke Treatment V. Special Section on Management of Aneurysmal Subarachnoid

Hemorrhage VI. Guidelines on the Establishment and Operation of Stroke Units VII. Guidelines for Stroke Rehabilitation VIII. Guidelines for Nursing Management of Stroke Patients IX. Strategy for Implementation of Guidelines X. Working Committees XI. List of Corporate Members

MESSAGE from the FOUNDING PRESIDENT These Guidelines for the Prevention, Treatment and Rehabilitation of Brain Attack is the output of the seven Stroke Congresses on Brain Attack organized by the Stroke Society of the Philippines. Aware of the many advances in research toward the prevention, treatment and rehabilitation of brain attack, the Stroke Society of the Philippines initiated the First Congress with the theme, “Thinking Globally, Acting Locally,” in October 1999. Since then, six more congresses have tackled the issue of organizing stroke services, and subsequently, intracerebral and subarachnoid hemorrhage. We worked on the principles that stroke is preventable through ways that may be implemented across all levels of society; that stroke is a “brain attack” needing emergency management where no allowance for worsening is tolerated; and that in the Philippine setting, the treatment should be optimal through proven, affordable, culturally acceptable and ethical means. With the panel of experts of the Stroke Society of the Philippines consisting of neurologists, internists, neurosurgeons, vascular surgeons and physiatrists, we worked with the practitioners in the field, identified by the Department of Health. The Guidelines were subjected to close scrutiny by experts and practitioners in the field, whose recommendations and comments were embodied in the final output. We realize that this is not a perfect document, but the Society is proud to present to our public these guidelines, which embody our best efforts to gather the latest, evidence-based data, and the opinion of experts in the Philippines. We continue to update the Guidelines as new knowledge comes to the forefront. We dedicate the Guidelines to our patients, students, practitioners and our health workers, that we may in our small way, contribute to the vision of “Health for All” in our beloved country. JOVEN R. CUANANG, MD Founding President Stroke Society of the Philippines

MESSAGE from the PRESIDENT The three revisions and four editions of these Guidelines for the Prevention, Treatment and Rehabilitation of Brain Attack since 1999 reflect the dynamic evolution of the management of cerebrovascular diseases and its outcomes in the last seven years. The latest data from the most recent trials have been incorporated into the previous guidelines, resulting in these updated Guidelines edition. Furthermore, there is a newly added section: The Establishment and Operation of Stroke Units. The working group of this fourth edition has strived hard to come out with this new document, a project and testament of the SSP of its commitment to our colleagues and to the fight against brain attack. ABDIAS V. AQUINO, MD President Stroke Society of the Philippines

Guidelines for PRIMARY and SECONDARY PREVENTION of STROKE

STROKE PREVENTION

Preface to the Guidelines on Primary and Secondary Prevention of Stroke

These practice guidelines provide an overview of the epidemiology and evidences associated with established and modifiable stroke risk factors, followed by recommendations for reducing stroke risk. These revised guidelines reflect current knowledge on primary and secondary stroke prevention.

The strategy in developing these guidelines was to utilize information from several existing national consensus and evidence-based guidelines to highlight significant associations between a risk factor and stroke and how modifying the risk factor through treatment or lifestyle modification can improve outcome. This knowledge would lead to proper recommendations.

The Stroke Prevention Writing Group members are active members of the Stroke Society of the Philippines and the Philippine Neurological Association invited by the committee chairs on the basis of each reviewer’s interest, training and previous work in the relevant topic areas. Members then updated the previous editions using recently published local data. The updated working paper was submitted for initial comments by the society members, and later to key opinion leaders and institutions.

Each major topic first discusses epidemiology (Section A) of a risk factor and its association with stroke, then highlights clinical trials or interventions on the risk factor for preventing stroke (Section B). When evidence is available, a separate subsection (Section B1) discusses primary- and secondary-prevention trials. Section C states the recommendations based on evidences.

When available, the strength of the recommendation are included and graded according to the American Heart Association (AHA)/American Stroke Association methods of classifying levels of certainty of the treatment effect and the class of evidence (Table 1).

Recommendations considered the cost-effective treatment of drugs with established efficacy.

These guidelines concentrated on modifiable risk factors: hypertension, diabetes, atrial fibrillation (AF) and other specific cardiac conditions, dyslipidemia, carotid artery stenosis, peripheral arterial disease, obesity, and lifestyle (exposure to cigarette smoke, excessive alcohol use, physical inactivity and unhealthy diet).

Other less well-documented or potentially modifiable risk factors are recognized. These include metabolic syndrome, drug abuse, oral contraceptive use, sleep-disordered breathing, migraine headache, hyperhomocysteinemia, hypercoagulability, inflammation and infection. Future editions may highlight these topics.

Because most strokes are cerebral infarcts, these recommendations focus primarily on the prevention of ischemic stroke or transient ischemic attack (TIA).

Although the primary outcome of interest is the prevention of stroke, many recommendations reflect the evidence on the reduction of all vascular outcome after stroke, including stroke, myocardial infarction (MI) and vascular death.

For secondary stroke prevention, the aim is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or TIA.

Table 1. Classes and Levels of Evidence Used in AHA Recommendations

Class I Conditions for which there is evidence for and/or general agreement that the procedure or treatment is useful and effective

Class II Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment

IIa Weight of evidence or opinion is in favor of the procedure or treatment.

IIb Usefulness/efficacy is less well established by evidence or opinion

Class III Conditions for which there is evidence and/or general agreement that the procedure or treatment is not useful/effective and in some cases may be harmful

Level of Evidence A: Data derived from multiple randomized clinical trials Level of Evidence B: Data derived from a single randomized trial or

nonrandomized studies Level of Evidence C: Expert opinion or case studies

I. HYPERTENSION Hypertension awareness, treatment and control remain low. Stroke mortality rates are predicted by the prevalence of hypertension. Yet compelling data show that first stroke can be prevented by blood pressure (BP) control, among others.1

A. Epidemiology: Hypertension is directly related to primary and secondary stroke risk. The higher the BP, the greater is the risk. Hypertension has a local prevalence of 17.4%2 and is the most important modifiable risk factor for stroke. The population attributable risk (PAR) of hypertension for stroke is high at around 25%.3 Hypertensive people are three to four times more likely to have a stroke than non-hypertensive people. Furthermore, both systolic and diastolic hypertensions are risk factors.

B. Risk Modification: Treatment of hypertension substantially reduces the risk of stroke. All classes of antihypertensive drugs are effective for BP control. A meta-analysis shows BP lowering confers a 30% to 40% stroke risk reduction. A 10 to 12 mmHg SBP reduction and a 5 to 6 mmHg DBP reduction confers relative reductions in stroke risk of 38%. The treatment of isolated systolic hypertension in the elderly decreases the risk for stroke by 36%.4 Furthermore, small BP reductions in a population may lead to substantial reductions in stroke risk: it is estimated that a population strategy to reduce systolic BP (SBP) by 2 mmHg will reduce stroke mortality by 6%.5 A 3-mmHg SBP reduction reduces risk by 8%. A 5-mmHg reduction reduces risk by 14%. Similar to other cardiovascular disorders, stroke reduction is progressive as BP is reduced to at least 115/75 mmHg.6 B1. Primary Stroke Prevention There is strong evidence that the control of high BP contributes to the prevention of stroke.5 The choice of antihypertensive agents should be individualized. BP reduction is generally more important than the specific agent used to achieve this goal. Hypertension remains undertreated in the community, and programs to improve treatment compliance need to be developed and supported. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) provides a comprehensive, evidence based approach to the classification and treatment of hypertension (Table 2).5

Table 2.Classification and management of BP for adults*

BP

Classification

SBP*

mmHg

DBP*

mmHg

Lifestyle

Modification

Initial drug therapy

Without

Compelling

Indication

With

Compelling

Indications

Normal <120 and

<80

Encourage No

antihypertensive

drug indicated.

Drug(s)for

compelling

indications.‡ Prehypertension 120-

139

or 80-

89

Yes

Stage 1

Hypertension

140-

159

or 90-

99

Yes

Thiazide-type

diuretics for

most. May

consider

ACEI, ARB,

BB, CCB, or

combination.

Drug(s)for the

compelling

indications.‡

Other

antihypertensive

drugs (diuretics,

ACEI, ARB,

BB, CCB) as

needed.

Stage 2

Hypertension

≥160 or

≥100

Yes Two-drug

combination for

most† (usually

thiazide-type

diuretic and

ACEI or ARB

or BB or CCB). DBP, diastolic blood pressure; SBP, systolic blood pressure. Drug abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BB, beta-blocker; CCB, calcium-channel blocker. *Treatment determined by highest BP category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.

‡Treat patients with chronic kidney disease or diabetes to BP goal of <80 mmHg.

B2. Secondary Stroke Prevention The overall decrease in stroke is related to the degree of BP lowering achieved. Meta-analyses of randomized controlled trials (RCTs) confirm an approximate 30% to 40% stroke reduction with BP lowering.7,8 Furthermore there is a continuous association of both SBP and DBP with the risk of ischemic stroke. The JNC 7 stresses the importance of lifestyle modifications in the overall management of hypertension. SBP reductions have been associated with weight loss; diet rich in fruits, vegetables and low-fat dairy products; regular aerobic physical activity; and limited alcohol consumption. Data on the relative benefits of specific antihypertensive regimens for secondary stroke prevention are largely lacking. A meta-analysis showed a significant reduction in recurrent stroke with diuretics and combined diuretics and angiotensin-converting enzyme (ACE) inhibitors (ACEIs), but not with beta-blockers (BBs) or ACEIs alone.9 Whether a particular class of antihypertensive drug or a particular drug within a given class offers an advantage in patients after ischemic stroke remains uncertain. With regard to stroke risk reduction, there may be beneficial non-BP-lowering properties of certain classes of BP-lowering agents, particularly from ACEIs and angiotensin-receptor blockers (ARBs).10,11 Among hypertensive diabetics, the use of ACEIs or ARBs reduces the risk of major vascular events and stroke by 24%. C. Recommendation:

C1. For primary prevention Regular screening for hypertension (at least every 2 years in most adults

and more frequently in minority populations and the elderly) and appropriate management (Class I, Level A), including dietary changes, lifestyle modification and pharmacological therapy as summarized in JNC 7, are recommended.

C2. For secondary prevention Antihypertensive treatment is recommended for both prevention of

recurrent stroke and of other vascular events in patients who have had an

ischemic stroke or TIA and are beyond the hyperacute period (Class I-A).12 Because this benefit extends to people with or without a history of hypertension, this recommendation should be considered for all ischemic stroke and TIA patients (Class IIa-B). The absolute target BP level and reduction are uncertain and should be individualized, but benefit has been associated with an average reduction of 10/5 mmHg, and normal BP levels have been defined as <120/80 mmHg by JNC 7 (Class IIa-B). BP should be adequately controlled in patients with hypertension. Physicians should check the BP of all patients at every visit. Patients with hypertension should be advised to monitor their BP at home.

Several lifestyle modifications have been associated with BP reductions and should be included as part of a comprehensive antihypertensive therapy (Class IIb-C).

The optimal drug regimen remains uncertain; however, the available data support the use of diuretics and the combination of diuretics and an ACEI (Class I-A). The choice of specific drugs and targets should be individualized on the basis of reviewed data and consideration of specific patient characteristics (e.g., extracranial cerebrovascular occlusive disease, renal impairment, cardiac disease or diabetes) (Class IIb-C). The Stroke Society of the Philippines supports the guidelines set forth by the Philippine Society of Hypertension and the JNC 7. Bibliography

1. Chapman N, Neal B. Blood pressure lowering for the prevention of first stroke. In: Chalmers J, ed. Clinician’s Manual on Blood Pressure and Stroke Prevention, 3rd ed. London: Science Press; 2002; p.21-31.

2. Sy RG, Dans AL, et al. Prevalence of Dyslipidemia, Diabetes, Hypertension, Stroke and Angina Pectoris in the Philippines. Phil J Med 2003;4D:1-6.

3. Gorelick PB. An integrated approach to stroke prevention. In: Chalmers J, ed. Clinician’s Manual on Blood Pressure and Stroke Prevention, 3rd ed. London: Science Press; 2002; p. 55-65.

4. SHEP Cooperative Research Group. Prevalence of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final result of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-3264

5. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-72.

6. Lawes CMM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and stroke. An overview of published reviews. Stroke 2004;35:1024-1033.

7. Yusuf S, Sleight P, Pogue J, Bosch J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145-153.

8. Lawes CMM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and stroke: an overview of published reviews. Stroke 2004;35:776-785.

9. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke 2003;34:2741-2748.

10. PROGRESS Collaborative Group. Randomized trial of a perindopril-based blood pressure lowering regimen among 6105 individuals with previous stroke or transient ischemic attack. Lancet 2001;358-1033-41.

11. Dahlof B. Deverux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE) a randomized trial against atenolol. Lancet 2002;359:995-1003.

12. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke [trunc]. Stroke 2006;37:577-617.

II. TRANSIENT ISCHEMIC ATTACK Conventionally, a person is diagnosed with stroke if neurological symptoms persist more than 24 hours; otherwise, a focal neurological deficit lasting <24 hours was defined as a TIA. However, with modern brain imaging, infarctions can be detected even in patients with brief symptoms. The most updated definition of stroke used by clinical trials is either symptoms lasting >24 hours or an acute clinically relevant brain lesion on imaging in patients with rapidly vanishing symptoms. The proposed new definition of TIA is a “brief episode of neurological dysfunction caused by a focal disturbance of brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of infarction.1

A. Epidemiology: Although TIA is most correctly considered a manifestation of cerebrovascular disease and not a stroke risk factor, it is an important predictor of future strokes. Reported 90-day stroke risk associated with TIA reaches 10.5%, and the highest risk is apparent in the first week.2 The risk is 4% to 8% in the first month, 12% to 13% in the first year, and 24% to 29% in 5 years.2-4 Patients with hemispheric TIA and carotid stenosis of more than 70% have a particularly poor prognosis, with a stroke rate of >40% in 2 years.4,5

B. Risk Modification: The distinction between TIA and ischemic stroke has become less important in recent years because many preventive approaches are applicable in both. As the risk factors for ischemic stroke and TIA are the same, the evidences supporting that modification of a particular risk factor are found in the corresponding sections in these guidelines. Many clinical trials have demonstrated that antiplatelets reduce stroke risk after TIA or minor stroke by 18% to 41%. RCTs on antiplatelet drugs that reduce stroke, either alone or as part of a composite of vascular outcomes, include aspirin, dipyridamole, aspirin-dipyridamole combination, ticlopidine, cilostazol and clopidogrel.6-8 Although some studies limited subjects to those with minor strokes instead of TIA, it is reasonable to consider a similar prophylactic effect in TIA patients. C. Recommendations: Efforts to increase public awareness and that of health workers regarding TIA and its significance should be maximized.

Evaluation of TIA should be attempted to define cause and determine prognosis and treatment. TIA patients should be expeditiously evaluated for vascular and cardiac risk factors for stroke. Hypertension, hyperlipidemia, diabetes, carotid stenosis and other modifiable risk factors should be treated, as outlined in these guidelines.

The cost and benefit of a drug should be considered when choosing an antiplatelet agent. Aspirin is the first choice unless contraindicated.

Patients who developed stroke recurrence while on aspirin, or those who cannot tolerate or have contraindications to aspirin may be given clopidogrel,

combined aspirin and dipyridamole, cilostazol, or other antiplatelets with RCT evidence of benefit. Aspirin is not recommended for primary stroke prevention, as this has no evidence especially among men.

While there is evidence of benefit of combined aspirin and clopidogrel in coronary heart disease or post-revascularization patients, this combination is not recommended for stroke prevention. Bibliography:

1. Albers GW, Caplan LR, Easton JD, et al.; for the TIA Working Group. Transient ischemic attack: proposal for a new definition. N Engl J Med 2002;347:1713-1716.

2. Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000;284:2901-2906.

3. Dennis M, Bamford J, Sandercock P, et al. Prognosis of Transient Ischemic Attacks in the Oxfordshire Community Stroke Project. Stroke 1990;21:848-853.

4. Whisnant JP, Wiebers DO. Clinical epidemiology of transient cerebral ischemic attacks (TIA) in the anterior and posterior circulation. In: Sundt TM Jr, ed. Occlusive Cerebrovascular Disease: Diagnosis and Surgical Management. Philadelphia, Pa: WB Saunders Co;1987:60-65.

5. Streifler JY, Benavente OR, Harbison JW, et al. Prognostic implications of retinal versus hemispheric TIA in patients with high grade stenosis: observations from NASCET. Stroke 1992;23:159. Abstract.

6. Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council. Stroke 2006;37:1583-1633.

7. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapy I: Prevention of death, MI, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81-106.

8. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. BMJ 2002;324:71-86.

APPENDIX OF TIA MANAGEMENT FOR STROKE PREVENTION

Since the 3rd edition of these guidelines, there have been several important trials related to antiplatelets and anticoagulants. The 2006 recommendations of the American Heart Association and the American Stroke Association are outlined below: ASA/AHA Recommendations for Antithrombotic Therapy for Noncardioembolic Stroke or TIA (Oral Anticoagulant and Antiplatelet Therapies)

For patients with noncardioembolic ischemic stroke or TIA, antiplatelet agents rather than oral anticoagulation are recommended to reduce the risk of recurrent stroke and other cardiovascular events (Class I-A).

Aspirin (50 to 325 mg/day), the combination of aspirin and extended-release dipyridamole, and clopidogrel are all acceptable options for initial therapy (Class IIa- A).

Compared with aspirin alone, both the combination of aspirin and extended-release dipyridamole and clopidogrel are safe.

The combination of aspirin and extended-release dipyridamole is suggested over aspirin alone (Class IIa-A).

Clopidogrel may be considered over aspirin alone on the basis of direct-comparison trials. Insufficient data are available to make evidence-based

recommendations with regard to choices between antiplatelet options other than aspirin. Selection of an antiplatelet agent should be individualized based on patient risk factor profiles, tolerance, and other clinical characteristics (Class IIb-B).

Addition of aspirin to clopidogrel increases the risk of hemorrhage and is not routinely recommended for ischemic stroke or TIA patients (Class III-A).

For patients allergic to aspirin, clopidogrel is reasonable (Class IIa-B).

For patients who have an ischemic cerebrovascular event while taking aspirin, there is no evidence that increasing the dose of aspirin provides additional benefit. Although alternative antiplatelet agents are often considered for noncardioembolic patients, no single agent or combination has been well studied in patients who have had an event while receiving aspirin. Reference: Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke [trunc]. Stroke 2006;37:577-617.

III. DIABETES MELLITUS A. Epidemiology: Diabetes mellitus (DM) is a serious public health problem in the Philippines. Estimated to affect 8% of the adult population worldwide, the local prevalence of DM (fasting blood sugar >125 mg/dL) according to the 2003 National Nutrition Health Survey1 is 4.6% (4.1% in males, 5% in females) while impaired fasting glucose is 3.2% (similar rates for males and females). People with type 2 DM have both an increased risk of atherosclerosis and increased prevalence of atherogenic risk factors (i.e., hypertension, obesity and abnormal blood lipids). DM is a definite risk factor for stroke.2 Case-control studies of stroke patients and prospective epidemiological studies have confirmed an independent effect of DM on ischemic stroke, increasing risk by 1.8- to nearly 6-fold.3 DM is frequently encountered in stroke care, being present in 15% to 33% of patients with ischemic stroke.4 The local RIFASAF case-control study showed a 1.6-fold higher risk for stroke among those with DM.5 However, data supporting DM as a risk factor for recurrent stroke are sparse. B. Risk Modification

B1. Primary Stroke Prevention DM has microvascular and macrovascular complications. Intensive DM

therapy delays the onset and slows down the progression of microvascular complications, such as retinopathy, nephropathy and neuropathy,6 but not macrovascular complications.7 Systematic review of RCTs on intensive insulin therapy (IIT) showed that IIT can decrease the occurrence of macrovascular events by up to 42%,8 including stroke, myocardial infarction (MI), angina and

claudication, among patients with type 1 DM. Sub-studies on diabetic patients included in drug trials show that the use of ACEIs9 and ARBs10 can reduce the combined outcome of MI, stroke and cardiovascular death by 21% to 33%. Similarly, ACEIs and ARBs decrease new-onset diabetes.

Primary stroke prevention guidelines have emphasized more rigorous BP control (target BP <130/80 mmHg) among both type 1 and type 2 diabetics.11 The American Diabetes Association (ADA) now recommends that all patients with diabetes and hypertension be treated with a regimen that includes either an ACEI or ARB.

Hyperlipidemia is a common comorbidity of diabetes. For any given cholesterol level, patients with diabetes have a greater frequency of cardiovascular events for which aggressive therapy of diabetic dyslipidemia is indicated, aiming for LDL<100 mg/dL or even up to 70 mg/dL among very high-risk groups.12 The use of statins among DM patients can reduce vascular events, including stroke.13,14 Addition of a statin for DM patients at high risk reduces stroke risk by 24%, and in those with one additional risk factor by 48%.

Among high-risk patients with type 2 DM, the thiazolidinedione, pioglitazone, seems to reduce the composite of all cause mortality, non-fatal stroke and MI, as well as reduce the need for insulin treatment.15

B2. Secondary Stroke Prevention Most of the available data on stroke prevention in DM patients pertain to

primary prevention. However, glycemic control is consistently recommended in multiple guidelines of both primary and secondary prevention of stroke and cardiovascular disease. Among patients with type 2 DM with or without vascular events, such as stroke, multifactorial approaches involving intensive treatments to control hyperglycemia, hypertension, dyslipidemia and microalbuminuria reduce the risk of cardiovascular events.16 These approaches included behavioral measures and the use of a statin, ACEI, ARB and antiplatelet drugs, as appropriate. The beneficial role of antiplatelets among stroke patients with or without diabetes has been proven in many trials.

C. Recommendation: A long-term, intensified DM control, which includes behavioral and pharmacological modification to prevent microvascular and macrovascular complications, is recommended.

Rigorous BP and lipid control should be considered in patients with diabetes (Class IIa-B). A target BP of <130/80 mmHg (Class I-A) is recommended as part of a comprehensive risk-reduction program. An ACEI or ARB is preferred for DM patients. Adults with DM, especially those with additional risk factors, should be treated with a statin to lower the risk of a first stroke (Class I-A).

Among diabetic patients with TIA or stroke, glucose control is recommended to near-normoglycemic levels to reduce microvascular complications (Class I-A) and possibly macrovascular complications (Class IIb-B). The goal for hemoglobin A1c should be 7% (Class IIa-B).

Bibliography

1. Dans AL, Morales DD, Abola TB, Roxas J, et al; for NNHeS 2003 Group. National Nutrition and Health Survey (NNHeS): Atherosclerosis-related Diseases and Risk Factors. Phil J Int Med 2005;43;103-115.

2. Abbott R, Donahue R, Macmahon S, et al. Diabetes and the Risk of Stroke. JAMA 1987;257:949-952. 3. American Heart Association/American Council on Stroke. Guidelines for Prevention of Stroke in

Patients with Ischemic Stroke or Transient Ischemic Attack. Stroke 2006;37:577-617. 4. Karapanayiotides T, Piechowski-Jozwiak B, van Melle G, Bogousslavsky J, Devuyst G. Stroke patterns,

etiology, and prognosis in patients with diabetes mellitus. Neurology 2004;62:1558-1562. 5. Roxas A; for the Philippine Neurological Association and Department of Health. Risk factors for stroke

among Filipinos. Phil J Neurol 2002;6:1-7. 6. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the

development of microvascular complications of diabetes mellitus. N Engl J Med 1993;329:304-309. 7. The Diabetes Control and Complications Trial (DCCT) Research Group. Effect of Intensive Diabetes

Management on Macrovascular Events and Risk Factors in the Diabetes Control and complications Trial. Am J Cardiol 1995;75:894-903.

8. United Kingdom Prospective Study (UKPDS) 33. Lancet 1998:352;837-853. 9. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus:

results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000;355:253-259.

10. Lindholm LH, Ibsen H. Dahlof B, et al; LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension Study (LIFE): a randomized trial against atenolol. Lancet 2002;359:1004-1010.

11. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-72.

12. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.

13. Collins R, Armitage J, Parish S, et al. For the Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 5963 people with diabetes: a randomized placebo-controlled trial. Lancet 2003;361:2005-2016.

14. Colhoun HM, Betteridge DJ, Durnington PN, et al; for CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicenter randomized placebo-controlled trial. Lancet 2004;364:685-696.

15. Gaede P, Parving HH, Pedersen O. The PROactive Study. Lancet 2006;367:23-24. 16. Gaede P, Vedel P, Larsen N, Jensen GV, et al. Multifactorial intervention and cardiovascular disease in

patients with type 2 Diabetes. N Engl J. Med. 2003; 348:383-393

IV. ATRIAL FIBRILLATION

A. Epidemiology: Non-valvular atrial fibrillation (NVAF) alone is associated with a three- to four-fold increase in stroke risk after adjustment for other vascular risk factors as shown in the Table 3.1

Table 3: Epidemiology of NVAF by Age Group1-6 Age group Prevalence PAR RR Risk reduction with treatment

50-59 y 0.5% 1.5% 4.0 Adjusted-dose warfarin vs control:

62% (CI 48%-72%); 6 trials,

n=2,900.

Aspirin vs placebo: 22% (CI 2%-

38%); 6 trials, n=3,119.

Adjusted-dose warfarin vs aspirin:

45% (CI 29%-57%): 6 trials,

n=4,025.

60-69 y 1.8 % 2.8% 2.6

70-79 y 4.8 % 9.9% 3.3

80-89 y 8.8% 23.5% 4.5

PAR, population-attributable risk; RR, relative risk. The prevalence of ischemic stroke for those with NVAF but without prior TIA or stroke is 2% to 4% per year.3,4

Table 3 also shows that the prevalence of NVAF increases with age. The mean age of NVAF patients is 75 years.1,5 Estimates of attributable risk reveal that about one quarter of strokes in the very elderly (>80 years old) are due to NVAF.1 NVAF is also associated with increased mortality after adjustment for other vascular risk factors partly because resultant strokes are large and disabling.7 B. Risk Modification RCTs have established the value of antithrombotic therapies, particularly warfarin and aspirin, in reducing stroke risk in patients with NVAF (Table 3). Adjusted-dose warfarin reduces stroke by 45% compared with aspirin.4

The absolute risk reduction from warfarin (from 4.5% for control down to 1.4% with treatment) means the prevention of 31 ischemic strokes each year for every 1,000 patients treated. Overall, warfarin is relatively safe, with a 1,3% annual rate of major bleeding compared with 1% for placebo or aspirin. The optimal international normalized ratio (INR) for stroke prevention in AF patients appears to be 2.0 to 3.0. The absolute risk of stroke varies 20-fold among AF patients, according to age and associated vascular diseases. Several stroke risk-stratification schemes have been developed and validated.8-10 The 2001 American College of Cardiology (ACC)/AHA/European Society of Cardiology (ESC) guidelines recommended anticoagulation for AF patients >60 years old and have a history of hypertension, DM, coronary artery disease (CAD), impaired left ventricular (LV) systolic function, heart failure or prior thromboembolism, and those >75 years old.11 This stratification scheme had not been prospectively validated even though the individual factors are validated. Since publication of the 2001 ACC/AHA/ESC guideline, the so-called CHADS2 stratification scheme has been proposed and validated.8 CHADS2 stands for Congestive heart failure (CHF), Hypertension, Age >75 years, DM, and prior Stroke or TIA. The CHADS2 score was derived from independent predictors of stroke risk in patients with NVAF as shown on Table 4. The score

gives 1 point each for CHF, hypertension, age >75 years, and DM; and 2 points for prior stroke or TIA. The score was validated in a large cohort study and in clinical trials.3,8,9 In this scheme, stroke risk of NVAF patients was reliably predicted as low (usually comprises half of patients), moderate (25% of patients) or high (25%).3 The validation study shows that patients with prior stroke or TIA and no other risk factors average 10.8 strokes per 100 patient-years, and that in the Stroke Prevention in Atrial Fibrillation (SPAF),12 patients with prior stroke or TIA without other risk factors had a stroke rate of 5.9%/year. Therefore, patients with stroke or TIA in the setting of AF should be treated with warfarin unless contraindicated. LV dysfunction, left atrial size, mitral annular calcification (MAC), spontaneous echo contrast, and left atrial thrombus by echocardiography also predict increased thromboembolic risk. Anticoagulation is particularly underused in elderly patients with NVAF.13 Although the attributable risk of stroke associated with AF increases with age,2 elderly (>75 years old) AF patients have about twice the risk of serious bleeding complications during anticoagulation compared with younger patients. Nevertheless, anticoagulation is still warranted if their risk of ischemic stroke without warfarin is greater than their risk of bleeding. In addition to age, poorly controlled hypertension and concomitant aspirin or non-steroidal anti-inflammatory drug use confer higher bleeding risk during anticoagulation. Therefore, age alone is not a contraindication to anticoagulation of high-risk AF patients. No data are available to address the question of when to initiate oral anticoagulation in an AF patient after a stroke or TIA. In general, initiation is recommended within 2 weeks of an ischemic stroke or TIA; however, for patients with large infarcts or uncontrolled hypertension, further delays may be appropriate. For AF patients with ischemic stroke or TIA despite therapeutic anticoagulation, no data indicate that either increasing the intensity of anticoagulation or adding an antiplatelet agent provides additional protection from future ischemic events.

Table 4: NVAF Risk Stratification and Treatment Recommendations: Risk Stratification by CHADS2 Scheme

CHADS2

Score*

Risk Level Stroke Rate

(%/year)

Treatment Recommendations

0

Low 1.0 Aspirin (75-325 mg/day)

1

Low-moderate 1.5 Warfarin INR 2.0-3.0 or aspirin (75-325

mg/day)†

2

Moderate 2.5 Warfarin INR 2.0-3.0†

3

High 5.0 Warfarin INR 2–3‡

>4 Very high >7.0

CHF, hypertension, age >75 years, or diabetes=1 point. Stroke or TIA=2 points. All NVAF patients with prior stroke or TIA should be considered high risk and treated with anticoagulants; the CHADS2 scheme should be applied for primary prevention. †Consider patient preferences, bleeding risk and access to good INR monitoring. For those with score=1, the number needed to treat with warfarin to prevent one stroke over 1 year is around 100. Excellent anticoagulation control is essential to achieve this benefit. ‡If patient is >75 years old, an INR target of 1.6 -2.5 is recommended by some experts. C. Recommendations: Antithrombotic therapy with warfarin or aspirin is recommended to prevent stroke in NVAF patients according to assessment of absolute stroke risk, estimated bleeding risk, patient preferences, and access to high-quality anticoagulation monitoring. For risk stratification and treatment recommendations, the CHADS2 scheme (Table 4) should be followed (Class I-A). Warfarin (INR=2.0-3.0) is recommended for high-risk (>4% annual stroke risk) AF patients provided there are no clinically significant contraindications to oral anticoagulants (Class I-A).

For patients with ischemic stroke or TIA with persistent or paroxysmal (intermittent) AF, anticoagulation with adjusted-dose warfarin (INR=2.5 [2.0-3.0] is recommended (Class I-A). In patients unable to take oral anticoagulants, aspirin 325 mg/day is recommended (Class I-A). Bibliography

1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke. The Framingham Study. Stroke 1991;22:983-988. 2. ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association. Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). J Am Coll Cardiol 1998;32:1486-1588. 3. Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA 2003;290:2685-2692. 4. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002;288:2441–2448. 5. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-2375. 6. Benjamin EJ, Wolf PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946-952. 7. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999;131:492-501. 8. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-2870. 9. Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004; 110:2287-2292. 10. Hart RG, Halperin JL, Pearce LA, et al.; Stroke Prevention in Atrial Fibrillation Investigators. Lessons from the Stroke Prevention in Atrial Fibrillation trials. Ann Intern Med 2003;138:831-838. 11. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA Task Force on Practice Guidelines; ESC Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation); North American Society of Pacing and Electrophysiology. ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary. A report of the ACC/AHA Task Force on Practice Guidelines and the ESC Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation)

Developed in Collaboration With the North American Society of Pacing and Electrophysiology. Circulation 2001;104:2118-2150. 12. Hart RG, Pearce LA, McBride R, et al. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999;30:1223-1229. 13. Hart RG. Warfarin in atrial fibrillation: underused in the elderly, often inappropriately used in the young. Heart 1999;82:539-540.

V. ACUTE MYOCARDIAL INFARCTION (WITH LEFT VENTRICULAR THROMBUS) AND CARDIOMYOPATHY Acute MI with LV Thrombus A. Epidemiology: Stroke or systemic embolism are less common among uncomplicated MI patients but can occur in up to 12% of patients with acute MI complicated by an LV thrombus. Acute MI is associated with up to 5% risk of ischemic stroke within 2 weeks. The rate is higher in those with anterior than inferior infarcts and may reach 20% in those with large anteroapical infarcts.1 The incidence of embolism is highest during the period of active thrombus formation in the first 1 to 3 months, yet the embolic risk remains substantial even beyond the acute phase in patients with persistent myocardial dysfunction, CHF or AF. B. Risk Modification: An overview of trials on anticoagulation after MI has shown that INR of 2.5 to 4.8 may increase hemorrhagic stroke 10-fold, whereas INR below 2.0 may not be effective in preventing ischemic stroke. An INR range of 2.0 to 3.0 with a target of 2.5 is recommended. Two studies of MI patients (n= 4,618) found that warfarin (INR=2.8-4.8) reduced ischemic stroke risk by 55% and 40%, respectively, compared with placebo, over 37 months.2,3 Statins for secondary prevention in patients with established atherosclerosis (CAD, thrombotic cerebral stroke, peripheral arterial disease or prior revascularization) significantly reduced overall risk of stroke, total mortality, cardiovascular death, MI and revascularization when total cholesterol is >190 mg/dL or LDL is >100 mg/dL. Stroke Prevention by Aggressive Reduction in Cholesterol Levels study (SPARCL) showed that patients previously documented to have stroke or TIA and no history of coronary heart disease benefited from atorvastatin 80 mg in reducing fatal stroke and TIA.4

C. Recommendations: Oral anticoagulation for MI patients is recommended if they have one or more of the following conditions: persistent AF, decreased LV function (e.g., ejection fraction [EF] 28%) or when LV thrombi are detected within several months after MI. Antiplatelets is not recommended to prevent a first stroke after an MI.

For patients with ischemic stroke or TIA due to acute MI in whom LV mural thrombus was identified by echocardiography or another form of cardiac imaging, oral anticoagulation is reasonable, aiming for an INR of 2.0 to 3.0 for at least 3

months and up to 1 year (Class IIa-B). Aspirin should be used concurrently for ischemic CAD during oral anticoagulant therapy in doses up to 160 mg/d (Class IIa-A). For patients with established atherosclerosis and total cholesterol >190 mg/dL or LDL >100 mg/dL, statins are recommended. Furthermore, adherence to the 2005 Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines is recommended.5

For patients with stroke or TIA but without coronary heart disease, statin therapy should be administered to prevent recurrence of stroke and TIA.

Cardiomyopathy A. Epidemiology: Two large studies found that the incidence of stroke is inversely proportional to EF.6,7 In the Survival and Ventricular Enlargement (SAVE) study, patients with EF of 29% to 35% (mean=32%) had a 0.8% stroke rate per year, whereas the yearly rate in those with EF <28% (mean=23%) was 1.7%. There was an 18% incremental increase in stroke risk for every 5% decline in EF. A retrospective analysis of data from the Studies of Left Ventricular Dysfunction (SOLVD) trial, which excluded patients with AF, found a 58% increase in risk of thromboembolic events for every 10% decrease in EF among women (p=0.01) but no increased risk in men.8 In patients with non-ischemic dilated cardiomyopathy, the rate of stroke appears similar to that associated with cardiomyopathy resulting from ischemic heart disease. B. Risk Modification: Warfarin is sometimes prescribed to prevent cardioembolic events in patients with cardiomyopathy. However, no RCT has demonstrated the efficacy of anticoagulation. Considerable controversy surrounds the use of warfarin in patients with cardiac failure or reduced LVEF.9,10 Warfarin appears to reduce the risk of ischemic stroke in patients with non-ischemic cardiomyopathy and in those with ischemic heart disease.11 Aspirin reduces the stroke rate by around 20%.12 Potential antiplatelet therapies used to prevent recurrent stroke include aspirin (50 to 325 mg/day), combined aspirin and extended-release dipyridamole (25mg/200 mg twice daily), and clopidogrel (75 mg daily). C. Recommendation: For patients with ischemic stroke or TIA who have dilated cardiomyopathy, either warfarin (INR=2.0-3.0) or antiplatelet therapy may be considered for prevention of recurrent events (Class IIb-C). Bibliography

1. Visser CA, Kan G, Meltzer RS, et al. Long-term follow-up of left ventricular thrombus after acute myocardial infarction: a two-dimensional echocardiographic study in 96 patients. Chest 1984;86:532-536.

2. Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group. Lancet 1994;343:499-503.

3. van Es RF, Jonker JJ, Verheugt FW, et al.; Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2) Research Group. Aspirin and coumadin after acute

coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002;360:109-113.

4. The SPARCL Investigators. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study. Cerebrovasc Dis. 2006;21(suppl 4):1. Abstract 1.

5. The Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 2005. Manila: The Philippine Heart Association Inc., Philippine College of Cardiology; 2005.

6. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992;327:669-677.

7. Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997;336:251-257.

8. Dries DL, Rosenberg YD, Waclawiw MA, Domanski MJ. Ejection fraction and risk of thromboembolic events in patients with sinus rhythm: evidence of gender difference in the studies of left ventricular dysfunction trial. J Am Coll Cardiol 1997;336:251-257.

9. Falk RH. A plea for clinical trial of anticoagulation in dilated cardiomyopathy. Am J Cardiol 1990;65:914-915.

10. Ezekowitz M. Antithrombotics for left ventricular impairment? Lancet 1998;351:1904. 11. Fuster V, Gersh BJ, Giuliani ER, et al. The natural history of idiopathic dilated cardiomyopathy. Am

J Cardiol 1981;47:525-531.

12. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin or both after myocardial infarction. N Engl J Med 2002;347:969-974.

VI. VALVULAR HEART DISEASE and PROSTHETIC HEART VALVES A. Epidemiology Annual rates of systemic thromboembolism (TE) in different valvular diseases are shown in Table 51-4: Table 5: Incidence of systemic thromboembolism in valvular heart disease

Alone

(No AF)

With AF

(vs without AF)

1. Prosthetic valve 20% Increased

2. Rheumatic mitral regurgitation 7.7% 22%

3. Rheumatic mitral stenosis 1.5%-4.0% Increased by 7-18x

4. Mitral valve prolapse <2% Increased

5. Aortic valve Not increased Increased

Patients with paroxysmal or persistent AF and valvular heart diseases such as mitral stenosis are at highest risk for future embolic events.

B. Risk Modification: Antithrombotic therapy can reduce the likelihood of stroke and systemic embolism in patients with valvular heart disease. The rate of TE in patients with mechanical heart valves is 4.4 per 100 patient-years without antithrombotic therapy; 2.2 per 100 patient-years with antiplatelet drugs; and 1 per 100 patient-years with warfarin. With or without AF, all patients with mechanical heart valves require anticoagulation with target anticoagulation levels varying according to type and position of the valve, and the presence of other risk

factors. The risk of TE in patients with native valvular heart diseases or mechanical or biological heart-valve prostheses must be balanced with the risk of bleeding. Nevertheless, because the frequency and permanency of consequences of TE events are usually greater than the outcome of hemorrhagic complications, anticoagulant therapy is generally recommended, particularly when associated with AF.5 Rheumatic Mitral Valve Disease a. Epidemiology: The annual rate of TE in rheumatic mitral regurgitation (MR) and stenosis (MS) without AF are 7.7% and 1.5% to 4% respectively. The presence of AF increases TE by 22% in MR patients and by seven- to 18-fold in MS patients.

Recurrent embolism occurs in 30% to 65% of patients with rheumatic mitral valve disease who have a history of a previous embolic event.6-8 Between 60% to 65% of these recurrences develop within the first year, most within 6 months.6,7

b. Risk Modification: Although not evaluated in randomized trials, multiple observational studies have reported that long-term anticoagulant therapy effectively reduces the risk of systemic embolism in patients with rheumatic mitral valve disease.3,9 Long-term anticoagulant therapy in patients with MS who had left atrial thrombus identified by transesophageal echocardiography can result in the disappearance of the thrombus.10

c. Recommendations: For patients with rheumatic mitral valve disease or prosthetic valve without prior stroke or TIA, oral anticoagulation with coumadin is recommended unless contraindicated.

For patients with ischemic stroke or TIA who have rheumatic mitral valve disease, whether or not AF is present, long-term warfarin therapy is reasonable, with a target INR of 2.5 (range; 2.0-3.0) (Class IIa-C).

Antiplatelet agents should not routinely be added to warfarin to avoid the additional bleeding risk (Class III-C). Aspirin 80 mg/day is suggested for patients with ischemic stroke or TIA with rheumatic mitral valve disease, whether or not AF is present, who have recurrent embolism while receiving warfarin (Class IIa-C)

Mitral Valve Prolapse a. Epidemiology: Mitral valve prolapse (MVP) is the most common form of valve disease in adults.11 Thromboembolic phenomena have been reported in patients with mitral valve prolapse in whom no other source could be found.12-16 The annual rate of TE in those with MVP and no AF is less than 2%. AF increases TE risk.

b. Risk Modification: No randomized trials have addressed the efficacy of selected antithrombotic therapies for this subgroup of stroke or TIA patients. The evidence on the efficacy of antiplatelet agents for general stroke and TIA patients was used to reach these recommendations. c. Recommendation: For patients with MVP who had ischemic stroke or TIA, antiplatelet therapy is reasonable (Class IIa-C). Mitral Annular Calcification a. Epidemiology: Although the incidence of systemic and cerebral embolism is not clear, thrombus has been found on heavily calcified annular tissue upon autopsy.17-22

b. Risk Modification: From observations and in the absence of randomized trials, anticoagulant therapy may be considered for patients with MAC and a history of TE. c. Recommendations: For patients with ischemic stroke or TIA in whom MAC is not documented to be calcific, antiplatelet therapy may be considered (Class IIb-C).

For patients with MR due to MAC and without AF, antiplatelet or warfarin therapy may be considered (Class IIb-C).

Aortic Valve Disease a. Epidemiology: Clinically detectable systemic embolism in isolated aortic valve disease is increasingly recognized because of microthrombi or calcific emboli.23 In an autopsy study of 165 patients with calcific aortic stenosis, systemic embolism was found in 31 patients (19%). In the absence of associated mitral valve disease or AF, systemic embolism in patients with aortic valve disease is uncommon. TE increases in patients with aortic valve disease.

b. Risk Modification: No randomized trials on selected patients with stroke and aortic valve disease exist. c. Recommendation: For patients with ischemic stroke or TIA and aortic valve disease but no AF, antiplatelet therapy may be considered (Class IIb-C) Prosthetic Heart Valves b. Epidemiology: The annual percentage of occurrence of systemic TE in those with prosthetic heart valves is 20%. The risk increases with AF. c. Risk Modification: A variety of mechanical heart valve prostheses are available for clinical use, all of which require antithrombotic prophylaxis. The most convincing evidence that oral anticoagulants are effective in patients with prosthetic heart valves comes from patients randomized to

treatment for 6 months with either warfarin in uncertain intensity or one of two aspirin-containing platelet-inhibitor regimens.24 In two randomized studies, concurrent treatment with dipyridamole and warfarin reduced the incidence of systemic embolism,25,26 and the combination of dipyridamole (450 mg/day) and aspirin (3.0 g/d) reduced the incidence of TE in patients with prosthetic heart valves.27 A randomized study of aspirin 1.0 g/day plus warfarin versus warfarin alone in 148 patients with prosthetic heart valves found a significant reduction of embolism in the aspirin-treated group.28 Another trial showed that the addition of aspirin 100 mg/day to warfarin (INR=3.0-4.5) improved efficacy compared with warfarin alone.29 The ESC guidelines recommend anticoagulant intensity in proportion to the TE risk associated with specific types of prosthetic heart valves.30 For first-generation valves, an INR of 3.0 to 4.5 was recommended; an INR of 3.0 to 3.5 was recommended for second-generation valves in the mitral position, whereas an INR of 2.5 to 3.0 was advised for second-generation valves in the aortic position. The 2004 American College of Chest Physicians recommended an INR of 2.5 to 3.5 for patients with mechanical prosthetic valves, and 2.0 to 3.0 for those with bioprosthetic valves and low-risk patients with bileaflet mechanical valves (such as the St. Jude Medical device) in the aortic position.31 Similar guidelines have been promulgated conjointly by the ACC and the AHA.11,32

d. Recommendations: For patients who have modern mechanical prosthetic heart valves, with or without ischemic stroke or TIA, oral anticoagulants should be administered to an INR target of 3.0 (range; 2.5-3.5) (Class I-B).

For patients with mechanical prosthetic heart valves who had an ischemic stroke or systemic embolism despite adequate therapy with oral anticoagulants, aspirin 75 to 100 mg/day in addition to oral anticoagulants and maintenance of the INR at 3.0 (range; 2.5-3.5) are reasonable (Class IIa-B).

For patients with ischemic stroke or TIA who have bioprosthetic heart valves with no other source of thromboembolism, anticoagulation with warfarin (INR=2.0-3.0) may be considered (Class IIb-C). Table 6. Summary of Recommendations for Patients With Cardioembolic Stroke or TIA

Risk Factor Recommendation Class/Level of

Evidence

AF For patients with ischemic stroke or TIA with

persistent or paroxysmal (intermittent) AF,

anticoagulation with adjusted-dose warfarin (target

INR=2.5 [2.0-3.0]) should be administered

Class I-A

In patients unable to take oral anticoagulants, aspirin

325 mg/day is recommended.

Class I-A

Acute MI and LV

thrombus

For patients with ischemic stroke caused by acute

MI with LV mural thrombus identified by

echocardiography or another form of cardiac

imaging, oral anticoagulation is reasonable

(INR=2.0-3.0 for at least 3 months up to 1 year).

Class IIa-B

Aspirin up to 160 mg/day (preferably enteric-coated)

should be used concurrently for patients with

ischemic CAD during oral anticoagulant therapy.

Class IIa-A

Cardiomyopathy For patients with ischemic stroke or TIA who have

dilated cardiomyopathy, either warfarin (INR=2.0-

3.0) or antiplatelet therapy may be considered to

prevent recurrent events.

Class IIb-C

MVP For patients with MVP who have ischemic stroke or

TIA, long-term antiplatelet therapy is reasonable.

Class IIa-C

MAC For patients with ischemic stroke or TIA and MAC

not documented to be calcific, antiplatelet therapy

may be considered.

Class IIb-C

Among patients with MR due to MAC, without AF,

antiplatelet or warfarin therapy may be considered.

Class IIb-C

Aortic valve

disease

For patients with ischemic stroke or TIA and aortic

valve disease who do not have AF, antiplatelet

therapy may be considered.

Class IIa-C

Prosthetic heart

valves

For patients with ischemic stroke or TIA who have

modern mechanical prosthetic heart valves, oral

anticoagulants are recommended, with an INR target

of 3.0 (range; 2.5-3.5).

Class I-B

For patients with mechanical prosthetic heart valves

who had an ischemic stroke or systemic embolism

despite adequate therapy with oral anticoagulants,

aspirin 75 to 100 mg/day in addition to oral

anticoagulants maintained at INR of 3.0 (range; 2.5-

3.5) is reasonable.

Class IIa-B

For patients with ischemic stroke or TIA who have

bioprosthetic heart valves with no other source of

TE, anticoagulation with warfarin (INR=2.0-3.0)

may be considered.

Class IIb-C

Bibliography

1. Israel DH, Sharma SK, Fuster V. Antithrombotic therapy in prosthetic heart valve replacement. Am Heart J 1994;127:400-411.

2. Israel DH, Fuster V, Ip JH, et al. Intracardiac thrombosis and systemic embolization. In: Colman RW, Hirsh J, Marder V, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed. Philadelphia, Pa: JB Lippincott; 1994:1452–1468.

3. Coulshed N, Epstein EJ, McKendrick CS, et al. Systemic embolism in mitral valve disease. Br Heart J 1970;32:26-34.

4. Wood JC, Conn HL Jr. Prevention of Systemic Arterial Embolism in Chronic Rheumatic Heart Disease by Means of Protracted Anticoagulant Therapy. Circulation 1954;10:517-523.

5. Devereaux PJ, Anderson DR, Gardner MJ, et al. Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. BMJ 2001;323:1218-1222.

6. Carter AB. Prognosis of cerebral embolism. Lancet 1965;2:514-519. 7. Wood P. Diseases of the Heart and Circulation. Philadelphia, Pa: JB Lippincott; 1956. 8. Levine HJ. Which atrial fibrillation patients should be on chronic anticoagulation? J Cardiovasc Med

1981;6:483-487. 9. Szekely P. Systemic embolization and anticoagulant prophylaxis in rheumatic heart disease. BMJ

1964;1:209-212. 10. Roy D, Marchand E, Gagne P, et al. Usefulness of anticoagulant therapy in the prevention of

embolic complications of atrial fibrillation. Am Heart J. 1986;112:1039-1043. 11. Bonow RO, Carabello B, De Leon AC, Jr., et al. ACC/AHA guidelines for the management of

patients with valvular heart disease. A report of the ACC/AHA Task Force on Practice Guidelines (Committee on Management of Patients With Valvular Heart Disease). J Am Coll Cardiol 1998;32:1486-1588.

12. Jeresaty RM. Mitral Valve Prolapse. New York, NY: Raven Press; 1979. 13. Barnett HJ. Transient cerebral ischemia: pathogenesis, prognosis, and management. Ann R Coll

Phys Surg Can 1974;7:153-173. 14. Barnett HJ, Jones MW, Boughner DR, Kostuk WJ. Cerebral ischemic events associated with

prolapsing mitral valve. Arch Neurol 1976;33:777-782. 15. Hirsowitz GS, Saffer D. Hemiplegia and the billowing mitral leaflet syndrome. J Neurol Neurosurg

Psychiatry 1978;41:381-383. 16. Saffro R, Talano JV. Transient ischemic attack associated with mitral systolic clicks. Arch Intern

Med 1979;139:693-694. 17. Hanson MR, Hodgman JR, Conomy JP. A study of stroke associated with prolapsed mitral valve.

Neurology 1978;23:341. 18. Fulkerson PK, Beaver BM, Auseon JC, Graber HL. Calcification of the mitral annulus: etiology,

clinical associations, complications and therapy. Am J Med 1979;66:967-77. 19. Kalman P, Depace NL, Kotler MN, et al. Mitral annular calcifications and echogenic densities in the

left ventricular outflow tract in association with cerebral ischemic events. Cardiovasc Ultrasonic 1982;1:155.

20. Nestico PF, Depace NL, Morganroth J, et al. Mitral annular calcification: clinical, pathophysiology, and echocardiographic review. Am Heart J. 1984;107(pt 1):989-996.

21. Kirk RS, Russell JG. Subvalvular calcification of mitral valve. Br Heart J 1969;31:684-692. 22. Ridolfi RL, Hutchins GM. Spontaneous calcific emboli from calcific mitral annulus fibrosus. Arch

Pathol Lab Med 1976;100:117-120. 23. Brockmeier LB, Adolph RJ, Gustin BW, Holmes JC, Sacks JG. Calcium emboli to the retinal artery

in calcific aortic stenosis. Am Heart J. 1981;101:32–37. 24. Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline aspirin for

the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial. Circulation 1985;72:1059-1063.

25. Chesebro JH, Fuster V, Elveback LR, et al. Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole. Am J Cardiol 1983;51:1537-1541.

26. Sullivan JM, Harken DE, Gorlin R. Pharmacologic control of thromboembolic complications of cardiac-valve replacement. N Engl J Med. 1971;284:1391–1394.

27. Taguchi K, Matsumura H, Washizu T, et al. Effect of athrombogenic therapy, especially high dose therapy of dipyridamole, after prosthetic valve replacement. J Cardiovasc Surg (Torino) 1975;16:8-15.

28. Dale J, Myhre E, Storstein O,et al. Prevention of arterial thromboembolism with acetylsalicylic acid: a controlled clinical study in patients with aortic ball valves. Am Heart J 1977;94:101-111.

29. Turpie AG, Gent M, Laupacis A, et al. Aspirin and warfarin after heart-valve replacement: a comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med 1993;329:524-529.

30. Gohlke-Barwolf C, Acar J, Oakley C, et al. Guidelines for prevention of thromboembolic events in valvular heart disease. Study Group of the Working Group on Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 1995;16:1320-1330.

31. Proceedings of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines. Chest 2004;126 (3 Suppl):172S-696S.

32. Bonow RO, Carabello B, de Leon AC Jr. et al. Guidelines for the management of patients with valvular heart disease: executive summary: a report of the ACC/AHA Task Force on Practice Guidelines (Committee on Management of Patients With Valvular Heart Disease). Circulation. 1998;98:1949-1984.

VII. CHOLESTEROL

A. Epidemiology: Epidemiological and observational studies have not shown a definite correlation between serum cholesterol levels and the incidence of stroke.1,2 According to the Asia Pacific Cohort Studies Collaboration,3 the relationship between cholesterol and stroke risk is more complex, with a stronger positive association with ischemic stroke and a weaker negative association with hemorrhagic stroke. However, this trend in hemorrhagic stroke was not seen in the HPS and combined data from the Long-term Intervention with Pravastatin in Ischaemic Disease study (LIPID) and the Cholesterol and Recurrent Event study. Furthermore, low cholesterol is common in patients with weight loss, severe handicap, or severe and chronic illness, which may be confounding factors for the demonstrated trend between hemorrhagic stroke and low total cholesterol. B. Risk Modification

B1. Primary Stroke Prevention A meta-analysis of 13 lipid-lowering trials prior to statin use showed no change in risk for total stroke.4 With the advent of statins, a meta-analysis of CARE, LIPID, HPS, the Scandinavian Simvastatin Survival Study (4S), the Prospective Study of Pravastatin in the Elderly at Risk study (PROSPER), the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the Kyushu Lipid Intervention Study (KLIS), the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE), and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that the overall relative risk reduction is 21% (ARR=9%).5 The greater the LDL reduction, the greater the intima-media thickness and stroke risk reduction.6

Statins conferred an important and large relative reduction in cardiovascular events including stroke among hypertensive patients who are not conventionally deemed dyslipidemic.7 Pretreatment with statins seem to reduce clinical severity in patients with stroke, especially among diabetics.8,9

B2. Secondary Stroke Prevention HPS showed a 19% reduction in major vascular events, but the decrease was due to reduction in coronary events and not in stroke recurrence.10 The Stroke Prevention with Aggressive Reduction of Cholesterol Levels (SPARCL), a large-scale statin RCT in patients with a history of stroke or TIA without CAD, and have mildly elevated lipid levels (mean LDL=133 mg/dL).11 The trial showed that atorvastatin 80 mg/day significantly reduced stroke by 16% in this patient subgroup.

Statins are likely to reduce stroke risk by stabilizing and /or repressing plaque. Statins also have pleiotropic (anti-inflammatory, antioxidant) effects that further justify their use in the primary and secondary prevention of cerebrovascular disease.12-14 Statins have a favorable safety profile and are not associated with increased hemorrhagic stroke or cancer risk.5 C. Recommendations

C1. Primary Stroke Prevention Therapeutic lifestyle changes are recommended as an essential modality

in clinical management.2 These include smoking cessation, weight management, regular physical activity and adequate BP monitoring and control.15 For patients at any level of cardiovascular risk, especially those with established atherosclerosis, a low-fat, low-cholesterol diet is recommended for life.

High-risk hypertensive patients and those with CAD should be treated with lifestyle measures and a statin, even with normal LDL levels (Class I-A).16,17

Adults with diabetes, especially those with additional risk factors, should receive statins to lower the risk of a first stroke (Class I-A).16

Patients with coronary artery disease and low HDL may be treated with weight reduction, increased physical activity, smoking cessation, and possibly niacin or fibrates (Class IIa-B).3,16

C2. Secondary Stroke Prevention Statins are recommended in patients with coronary heart disease or

symptomatic atherosclerotic disease to lower cholesterol levels to LDL<100 mg/dL (<70 mg/dL for very high-risk persons) (Class I-A).16,18-20

Patients with ischemic stroke or TIA presumed to be due to atherosclerosis but without preexisting indications for statins are reasonable candidates for statin treatment to reduce the risk of vascular events (Class IIa-B).16

Patients with ischemic stroke or TIA and low HDL may be considered for treatment with niacin or fibrates (Class IIb-B).3,16

Lastly, adherence to the statements of the 2005 Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines is recommended. These are15: 1. To reduce the overall cardiovascular risk, all patients, regardless of their present morbid condition or risk profile, should be advised on the need for the following:

Smoking cessation;

Weight management;

Regular physical activity; and

Adequate blood pressure monitoring and control.

2. For patients at any level of cardiovascular risk, especially those with established atherosclerosis, a low-fat, low-cholesterol diet is recommended for life. 3. In poorly nourished and elderly patients, correction of nutritional deficiencies can be achieved even with a low-fat, low-cholesterol diet. 4. For low-risk patients without evidence of atherosclerosis, drug therapy is not recommended, regardless of lipid levels. Risk factors include hypertension, familial hypercholesterolemia, left ventricular hypertrophy, smoking, family history of premature CAD, male sex, age >55 years, proteinuria, microalbuminuria, BMI ≥25. Low risk patients have <3 risk factors. The presence of familiar hypercholesterolemia warrants treatment even without other risk factors. 5. For patients without established atherosclerosis but with ≥3 risk factors and total cholesterol ≥190 mg/dL or LDL ≥100 mg/dL, statins may be recommended. 6. For diabetic patients without evidence of atherosclerosis and with total cholesterol ≥190 mg/dL or LDL ≥100 mg/dL, statins are recommended. 7. Fibrates may be recommended as an alternative to statins in diabetic patients with HDL ≤35 mg/dL and LDL ≤90 mg/dL. 8. For patients with established atherosclerosis and total cholesterol ≥190 mg/dL or LDL ≥100 mg/dL, statins are recommended. 9. Fibrates may be recommended as an alternative to statins if HDL ≤35 mg/dL and LDL ≤90 mg/dL. 10. In patients without risk factors and history or symptoms of established atherosclerosis, screening for lipid levels is not recommended. 11. In patients without established atherosclerosis but with ≥3 risk factors, lipid profile may be recommended. 12. In patients with established atherosclerosis or diabetes, the use of lipid profile for screening is recommended. Bibliography

1. Di Napoli M. Benefits of statins in cerebrovascular disease. Curr Opin Investig Drugs 2004;5:295-305.

2. Cheung BM, Lauder IJ, Lau CP, Kumana CR. Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. Br J Clin Pharmacol 2004;57:640-651.

3. Zhang X, Patel A, Horibe H, et al.; Asia Pacific Cohort Studies Collaboration. Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. Int J Epidemiol 2003;32:563-572.

4. Atkins D, Psaty BM, Koepsell TD, et al. Cholesterol reduction and the risk for stroke in men. A meta-analysis of randomized, controlled trials. Ann Intern Med 1993;119:136-145.

5. Amarenco P, Lavallee PC, Labreuche J, et al. Stroke prevention, blood cholesterol and statins. Acta Neurol Taiwan 2005;14:96-112.

6. Amarenco P. Effect of statins in stroke prevention. Curr Opin Lipidol 2005;16:614-618. 7. Sever PS, Dahlof B, Poulter NR, et al.; ASCOT investigators. Prevention of coronary and stroke

events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361:1149-1158.

8. Greisenegger S, Mullner M, Tentschert S, et al. Effect of pretreatment with statins on the severity of acute ischemic cerebrovascular events. J Neurol Sci 2004;221:5-10.

9. Colhoun HM, Betteridge DJ, Durrington PN, et al.; CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696.

10. Heart Protection Study Collaborative Group. Effect of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004;363:757-767.

11. The SPARCL Investigators. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study. Cerebrovasc Dis. 2006;21(suppl 4):1. Abstract 1.

12. Vaughan CJ. Prevention of stroke and dementia with statins: Effects beyond lipid lowering. Am J Cardiol 2003;91:23B-29B.

13. Welch KMA. Statins for the prevention of cerebrovascular disease: the rationale for robust intervention. Eur Heart J Suppl 2004;6 (Suppl C):C34-C42.

14. Martin-Ventura JL, Blanco-Colio LM, Gomez-Hernandez A, et al. Intensive treatment with atorvastatin reduces inflammation in mononuclear cells and human atherosclerotic lesions in one month. Stroke 2005;36:1796-1800.

15. The Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 2005. Manila: The Philippine Heart Association Inc., Philippine College of Cardiology; 2005.

16. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke [trunc]. Stroke 2006;37:577-617.

17. Corvol JC, Bouzamondo A, Sirol M, et al. Differential effects of lipid-lowering therapies on stroke prevention: a meta-analysis of randomized trials. Arch Intern Med 2003;163:669-676.

18. LaRosa JC, Grundy SM, Waters DD, et al.; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435.

19. Waters DD, Schwartz GG, Olsson AG, et al.; MIRACL Study Investigators. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Circulation 2002;106:1690-1695.

20. Grundy SM, Cleeman JI, Merz CN, et al.; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239.

VIII. CAROTID STENOSIS A. Epidemiology: Extracranial carotid artery disease accounts for 15% to 20% of all ischemic strokes.1 Individuals with carotid stenosis often have more widespread atherosclerotic disease with a high prevalence of coronary heart disease and claudication.2,3

The stroke risk due to carotid artery stenosis is determined primarily by symptom status and is related to lesion severity. Patients with symptomatic severe carotid stenosis have an annual stroke risk of 13% to 15%, compared with 1% to 2% in those with no history of prior stroke or TIA or those with asymptomatic lesions.4-6 In addition, echolucent or ulcerated plaques, hypertension and progressive lesions are associated with increased risk of neurological events.7

B. Risk Modification

B1. Primary Stroke Prevention The role of carotid endarterectomy (CEA) in asymptomatic cases requires

special consideration. Among patients with asymptomatic carotid artery stenosis of 60% to 99% enrolled in the Asymptomatic Carotid Artery Stenosis Study (ACAS), CEA combined with best medical treatment reduced the 5-year ipsilateral-stroke risk from 11% to 5.1% (RRR=53%).5 The Asymptomatic Carotid Surgery Trial (ACST) supports the results of ACAS, showing a small but definite reduction in the risk of stroke with surgery among patients with at least 60% stenosis (5-year stroke risk of 11.8% in the medical arm compared with 6.4% in the combined CEA and medical treatment arm).6 For asymptomatic patients to benefit from surgery, there should be a exceptionally low perioperative complication rate (< 3%).5-7

Neither ACAS nor ACST showed increasing benefit from surgery with increasing degree of asymptomatic stenosis within the 60%-to-99% range.5,6,8

B2. Secondary Stroke Prevention Among symptomatic patients with 70% stenosis or greater but without

near occlusion, combined CEA and medical treatment provide up to 16% absolute-risk reduction or 61% relative-risk reduction in ipsilateral and perioperative stroke over medical treatment alone (over 5 years).4,9-11

There was a trend toward benefit with surgery at 2 years (ARR=5.6 %) among patients with near-total carotid occlusion, but this was seen only for in the short term (-1.7% over 5 years).9

CEA was harmful for symptomatic patients with less than 30% stenosis. It had had no effect among patients with 30% to 49% stenosis, and was of marginal benefit in patients with 50% to 69% stenosis. Greater benefit was seen in men, those >75 years old, those with hemispheric symptoms (compared with those with transient monocular blindness) and those were randomized within 2 weeks of a TIA or a non-disabling ischemic stroke.4,9-11

Meta-analysis of five completed or terminated RCTs comparing endovascular treatment and CEA (Carotid and Vertebral Artery Transluminal Angioplasty Study [CAVATAS], Kentucky, Leicester, Wallstent, Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy [SAPPHIRE]) found no difference in the odds of death or any stroke at 30 days and at one year between the two groups.12 As yet, there is no evidence on the long-term efficacy of angioplasty and stenting available from any of the studies. Several international trials such as the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST),13 International Carotid Stenting Study (ICSS),14 Stent-protected Percutaneous Angioplasty of the Carotid versus Endarterectomy (SPACE)15 and Endarterectomy versus Angioplasty in patients with severe Symptomatic Stenosis (EVA-3s)16 are awaiting completion.

C. Recommendations: Antiplatelets, statins and modification of stroke risk factors for all patients with carotid artery disease (Class I-C). At present, mass screening for high-grade asymptomatic carotid stenosis is not cost-effective. However it is reasonable to do screening using non-invasive tests (e.g., carotid duplex) in patients at risk for significant carotid disease, such as those who survived a stroke, or those who have carotid bruit, peripheral vascular disease, and/or CAD. It is also reasonable to consider CEA for patients with asymptomatic stenosis of >60% if the patient has a life expectancy of at least 5 years and the perioperative risk can be reliably documented to be <3% (Class I-A). CEA combined with optimal medical management is recommended for patients with recent TIA or stroke and ipsilateral severe carotid artery stenosis (70%-99%) if perioperative risk of <6% can be attained (Class I-A). For symptomatic patients with 50% to 69% stenosis, CEA is recommended depending on patient-specific factors, such as age, gender, comorbidities and severity of initial symptoms (Class I-A). When the degree of stenosis is <50%, there is no indication for CEA (Class III-A).17,18 Since benefit from CEA is dependent on the degree of stenosis, measurement must be accurate and reliable. In deciding for surgical intervention, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method of angiographically defining the degree of stenosis is recommended (i.e., % stenosis = {1-[diameter of stenosis/diameter of distal internal carotid artery]} x 100%).19 In patients with concomitant carotid and coronary artery disease, available data at this time are insufficient to declare superiority of timing CEA either before or simultaneous with coronary-artery bypass grafting (CABG). Unless results of ongoing studies are reported, carotid angioplasty and stenting (CAS) remains to be a second option to CEA. The endovascular approach is favored in certain cases (e.g., stenosis is difficult to access surgically; restenosis after CEA or medical conditions exist that greatly increase the risk of surgery) (Class IIb-B). CAS is reasonable when performed by operators with established periprocedural morbidity and mortality rates of <6% (Class IIb-B).18 Bibliography

1. Sacco RL, Ellenberg JA, Mohr JP, et al. Infarcts of undetermined cause: the NINDS Stroke Data Bank. Ann Neuro 1989;25:382-390.

2. Hertzner, HR, Young JR, Beven EG, et al. Coronary angiography in 506 patients with extracranial cerebrovascular disease. Arch Intern Med 1985;145:849-852.

3. Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: a review. Stroke 1986;17:648-645.

4. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1998;339:1415-1425.

5. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid arterectomy stenosis. JAMA 1995;273:1421-1428.

6. MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomized controlled trial. Lancet 2004;363:1491-1502.

7. Liapis C, Kakisis J and Kostakis, A. Carotid stenosis: Factors affecting symptomatology. Stroke 2001;32:2782-2786.

8. Rothwell PM and Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: Asymptomatic carotid surgery trial. Stroke 2004;35:2425-2427.

9. Rothwell PM, Eliasziw M. Gutnikov SA for the Carotid Endarterectomy Trialists’ Collaboration. Analysis of pooled data from the randomized controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003;361:107-116.

10. Farrel B, Fraser A, Sandercock P, et al. Randomized trial of endarterectomy for recently symptomatic carotid stenosis. Final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379-1387.

11. Mayberg MR, Wilson E, Yatsu F, et al. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. JAMA 1991;226:3289-3284.

12. Coward L, Featherstone R, Brown M. Safety and efficacy of endovascular treatment of carotid artery stenosis compared with carotid endarterectomy. A Cochrane systematic review of the randomized evidence. Stroke 2005;36:905-911.

13. Hobson RW. CREST (Carotid Revascularization Endarterectomy versus Stent Trial): background, design and current status. Semin Vasc Surg 2000;14:139-143.

14. Featherstone RL, Brown MM, Coward LJ. International carotid stenting study: protocol for a randomized clinical trial comparing carotid stenting with endarterectomy in symptomatic carotid artery stenosis. Cerebrovasc Dis 2004;18:69-74.

15. Ringleb PA, Kunze A, Allenberg JR, et al. The Stent-Supported Percutaneous Angioplasty of the Carotid Artery vs Endarterectomy Trial. Cerebrovasc Dis 2004;18:66-68.

16. EVA 3S Investigators. Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA 3S). Cerebrovasc Dis 2004;18:62-65.

17. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy – an evidence based review. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005;65:794-801.

18. Sacco R, Adams R, Albers G, et al. Guidelines for the Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke 2006;37:577-617.

19. Barnett HJM, Warlow CP. Carotid endarterectomy and the measurement of stenosis. Stroke 1993;24:1281-1284.

IX. INTRACRANIAL STENOSIS A. Epidemiology: Atherosclerotic intracranial stenoses are responsible for ischemic stroke in 5% to 10% of Caucasian patients, and in up to 33% of Asian, Hispanic and African patients.1-6 Other risk factors for intracranial atherosclerosis include age, hypertension, smoking, diabetes, lipid disorders and metabolic syndrome.7-12

The annual risk of stroke among patients with symptomatic intracranial stenosis ranges from 3% to 15% (approximate annual values are: 7.6% for the carotid siphon, 7.8% for the middle cerebral artery [MCA], 2%-7% for the vertebral artery and 11% in the basilar artery).13-18 In contrast, asymptomatic MCA stenosis appears to have a benign prognosis with a low risk of ipsilateral stroke (1.4% annually) in medically treated Caucasian patients.19-20

B. Risk Modification: There is currently no data available. Among patients with stroke or TIA caused by a 50% to 99% stenosis of a major intracranial artery, the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) study showed that warfarin does not confer an advantage over aspirin in terms of stroke reduction (2-year ischemic stroke rate of 19.7% for aspirin vs. 17.2% for warfarin).16

In the Trial of cilOstazol in Symptomatic intracranial arterial Stenosis (TOSS), adding cilostazol to aspirin was superior to aspirin monotherapy in preventing progression of intracranial arterial stenosis.21 Continued trials are warranted to confirm the efficacy of cilostazol in preventing progression and further vascular events in patients with symptomatic intracranial arterial stenosis.

The EC-IC Bypass Trial failed to show clinical benefit of revascularization procedure (extracranial-intracranial anastomosis) in patients with atherosclerotic disease of the carotid artery and MCA.17 Bypass-patency rate was 96%, but fatal and non-fatal stroke occurred more frequently and earlier among those randomized to surgery.

Single-center experiences suggest that intracranial angioplasty and/or stenting can be performed with a high degree of technical success.22 Acceptable anatomical and clinical results of up to 6 months were obtained in small groups of medically refractory patients with strokes attributable to intracranial stenosis enrolled in the Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA) and WingSpan trials.23-24 Further studies are needed in larger cohorts with longer follow-up periods to fully determine the effectiveness of interventional catheter-based procedures for intracranial stenosis.

C. Recommendation: Patients with intracranial stenosis should be counseled regarding optimal medical therapy (antiplatelets, statins) and aggressive management of stroke risk factors.22,25

Further studies are warranted to evaluate short and long-term efficacy of angioplasty and or stenting in patients with hemodynamically significant intracranial stenosis (>50%) and symptoms despite medical therapy.25 (Class IIb-C) Bibliography

1. Gorelick PB. Distribution of atherosclerotic cerebrovascular lesions. Effects of age, race, and sex. Stroke 1993;24 (12 Suppl):I16-I19.

2. Sacco, RL, Kargman DE, Gu Q, Zamanillo MC. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 1995;26:14-20.

3. Wityk RJ. Lehman D, Klag M, et al. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 1996;27:1974-1980.

4. Wong, KS, Huan L. Racial distribution of intracranial and extracranial atherosclerosis. J Clin Neurosc 2003;10:30-34.

5. Leung SY, Ng TH, Yuen ST, et al. Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels. Stroke 1993;24:779-786.

6. Suh DC, Lee SH, Kim KR, et al. Pattern of atherosclerotic carotid stenosis in Korean Patients with stroke: different involvement of intracranial versus extracranial vessels. Am J Neuroradiol 2003;24:239-244.

7. Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: a review: Stroke 1986;17:648-655.

8. Cho, SJ, Sohn YH, Kim JH. Blood flow velocity changes in the middle cerebral artery as an index of chronicity of hypertension. J Neuro Sci 1997;150:77-80.

9. Ingall TJ, Homer D, Baker HL Jr, et al. Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels. Arch Neurol 1991;48:687-691.

10. Inzitari D, Hachinski VC, Taylor DW, Barnett HJ. Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors. Arch Neurol 1990;47:1080-1084.

11. Arenillas JF, Molina CA, Chacon P, et al. High lipoprotein, diabetes and the extent of symptomatic intracranial stenosis. Neurology 2004;63:27-32.

12. Bang Oy, Kim JW, Lee JH, et al. Association of the metabolic syndrome with intracranial atherosclerotic stroke. Neurology 2005;65:296-298.

13. Thijs VN, Albers GW. Symptomatic intracranial atherosclerosis: Outcome of patients who fail antithrombotic therapy. Neurology 2000;55:490-497.

14. Rundek T, Elkind MS, Chen X. Increased early stroke recurrence among patients with extracranial and intracranial atherosclerosis: Northern Manhattan Stroke Study. Neurology 1998;50 (Suppl 4):A75.

15. The WASID Study Group. Prognosis of patients with symptomatic vertebral or basilar artery stenosis. Stroke 1998;29:1389-1392.

16. Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005;352:1305-1316.

17. The EC-IC Bypass Study Group. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. N Eng J Med 1985;313:1191-1200.

18. Wechler LR. Kristler JP, David KR. Kaminsky MJ. The prognosis of carotid siphon stenosis. Stroke 1986;17:714-718.

19. Kremer C, Schaettin T, Giorgiadis D, Baumgartner R. Prognosis of asymptomatic stenosis of the middle cerebral artery. J Neurol Neurosurg Psychiatry 2004;75:1300-1303.

20. Kern R, Steinke W, Daffertshofer M, et al. Stroke recurrence in patients with symptomatic versus asymptomatic middle cerebral artery disease. Neurology 2005;65:859-864.

21. Kwon S, Cho YJ, Koo JS et al. Cilostazol prevents the progression of symptomatic intracranial stenosis. Stroke 2005;36:782-786.

22. Higashida R, Meyers PM, Connors J, et al. Intracranial angioplasty and stenting for cerebral atherosclerosis: A Position Statement of the American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, and the American Society of Neuroradiology. J Vasc Interv Radiol 2005;16:1281-1285.

23. SSLYVIA Study Investigators. Stenting of symptomatic atherosclerotic lesions in the vertebral or intracranial arteries (SSYLVIA). Stroke 2004;35:1388-1392.

24. Henkes H, Miloslavski E, Lowens S, et al. Treatment of intracranial atherosclerotic stenosis with balloon dilatation and self-expanding stent deployment (WingSpan). Neuroradiology 2005;47:222-228.

25. Sacco R, Adams R, Albers G, et al. Guidelines for the Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke 2006; 37:577-617.

X. SMOKING

A. Epidemiology

A1. Prevalence Asian countries have the highest prevalence of smoking in the world: 72%

in Korean men, 63% in Chinese men and 58% in Japanese men.1 The 2003 NNHeS survey showed that the prevalence of smoking in Filipinos is 56.3% in males and 12.1% in females.2 Two national surveys on Filipino adolescents revealed that one in five adolescents current smoking, males having a higher rate than females (37.3% vs. 6.3%).3,4

A2. Smoking as Stroke Risk Factor

A meta-analysis of 32 studies estimated the relative risk for cerebral infarct to be 1.9 for smokers versus nonsmokers.5 Case control and prospective studies have shown that cigarette smoking is an independent predictor of stroke, with a dose-response relationship affecting both men and women.6-8 The Framingham Heart Study showed that the relative risk of stroke in heavy smokers (>40 cigarettes/day) was twice that of light smokers (<10 cigarettes/day), and the risk increased with the number of cigarettes smoked.9 The large cohort study of U.S. male physicians showed heavy smokers (>20 cigarettes/day) had a relative risk of 2.71 for total nonfatal stroke, and 1,46 for fatal stroke.10 Studies also suggest a dose-response relationship between pack-years of smoking and carotid-artery intima-media wall thickness.11 Smoking only one cigarette increases heart rate, blood pressure and cardiac index, and decreases arterial distensibility.12 In addition, both active and passive smoke are associated with the development of atherosclerosis.13

Stroke also increases the risk of hemorrhagic stroke. In men, current smokers of <20 cigarettes/day had relatives risks of 1.65 for total hemorrhagic strokes, 1.60 for intracerebral hemorrhage (ICH), and 1.75 for subarachnoid hemorrhage (SAH) compared to those who never smoked.14 Current smokers of >20 cigarettes/day had relative risks of 2.36 for total hemorrhagic stroke, 2.06 for ICH and 3.22 for SAH. In women, current smokers of <15 cigarettes/day had a relative risks of 1.93 for total hemorrhagic stroke, 2.5 for ICH and 1.70 for SAH.15 Women who smoked >15 cigarettes/day had relative risks of 3.29 for total hemorrhagic stroke, 2.67 for ICH and 4.02 for SAH.

A3. Smoking Potentiates Effects of Other Stroke Risk Factors

A synergistic effect on the risk of cerebral infarction exists between the use of oral contraceptives (OC) and smoking. With nonsmoking women who do not use OC as reference group, the odds for cerebral infarction were 1.3 times greater for women who smoked but did not use OC, 2.1 times greater for nonsmoking OC users, and 7.2 times greater for OC users who smoked.16 A similar impact on hemorrhagic stroke is observed. The odds for hemorrhagic stroke were 1.6 times greater for women smoked but did not use OC, 1.5 times greater for nonsmoking OC users, and 3.7 times greater for OC users who smoked.17

A4. Environmental Tobacco Smoke and Passive Smoking Like outdoor air pollution, the effects of second-hand smoke are large and rapid. Several studies suggest that environmental tobacco smoke is a substantial risk factor for stroke, with risk approaching the doubling found seen with active smoking.18 Passive smoking may exert detrimental effects on vascular homoeostasis. Cohort studies showed an elevated prevalence of stroke among women nonsmokers living with husbands who smoked, and prevalence increased with increasing intensity and duration of husbands’ smoking.19

B. Risk Modification: Both the Framingham Heart Study and the Nurses Health Study showed that 5 years after cessation of smoking, risk ratios normalized.9,20 However, another study showed that the risk reduction was dependent on the quantity of cigarettes smoked before stopping: light smokers (<20 cigarettes/day) reverted back to normal values but heavy smokers retained twice the incidence of stroke as non smokers.21 Switching to pipe or cigar smoking confers little benefit, emphasizing the need for complete cessation of smoking.22 A combination of nicotine replacement therapy, social support and skills training seems to be the most effective approach to smoking cessation.23,24 C. Recommendations: Smoking cessation for all current smokers is recommended (Class I-C).25 Nonsmokers are also advised not to start smoking. Exposure to environmental tobacco smoke should be minimized (Class IIa-C). Republic Act No. 9211 or The Tobacco Regulation Act of 2003 should be implemented to protect the populace from hazardous products, promote the right to health and instill health consciousness. Effective behavioral and pharmacological treatments should be advised and encouraged for nicotine dependence (Class IIa-B).

Bibliography

1. Jee S, Suh I, Kim IS, et al. Smoking and atherosclerotic cardiovascular disease in men with low levels of serum cholesterol. The Korea Medical Insurance Corporation Study. JAMA 1999;282:2149-2155.

2. Dans AL, Morales DD, Abola TB, Roxas J, et al; for NNHeS 2003 Group. National Nutrition and Health Survey (NNHeS): Atherosclerosis-related Diseases and Risk Factors. Phil J Int Med 2005;43;103-115.

3. UP Population Institute. YAFS 2 (Young Adult Fertility and Sexuality Study). 1994. 4. UP Population Institute.YAFS 3 (Young Adult Fertility and Sexuality Study). 2002. 5. Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ

1989;298:789-794. 6. Bonita R, Seragg R, Stewart A, et al. Cigarette smoking and risk of premature stroke in men and

women. BMJ 1987;293;6-8. 7. Abott RD, Yin Yin MA, Reed DM, et al. Risk of stroke in male cigarette smokers. N Engl J Med

1986;315:717-720. 8. Colditz GA, Bonita R, Stampfer MJ, et al. Cigarette smoking as a risk factor for stroke. Framingham

Study. JAMA 1988:318:937-941. 9. Wolf PA, D'Agostino RB, Kannel WB, et al. Cigarette smoking as a risk factor for stroke. The

Framingham Study. JAMA 1988;259:1025-1029. 10. Robbins AS, Manson JE, Lee I, et al. Cigarette smoking and stroke in a cohort of US male physicians.

Ann Intern Med 1994;120:458-462. 11. Howard G, Burke GL, Szklo M, et al. Active and passive smoking are associated with increased carotid

wall thickness. The atherosclerotic risk in community study. Arch Intern Med 1994;154:1277-1282. 12. Kool MJ, Hoeks AP, Struijker Boudier HA, et al. Short- and long-term effects of smoking on arterial wall

properties in habitual smokers. J Am Coll Cardiol 1993;22:1881-1886. 13. Howard G, Wageknecht LE, Burker GL, et al. Cigarette smoking and progression of atherosclerosis: the

Atherosclerosis Risk in Communities (ARIC) Study. JAMA 1998;279:119-124. 14. Kurth T, Kase C, Nerger K, et al. Smoking and risk of hemorrhagic stroke in men. Stroke 2003;34;1151-

1155. 15. Kurth T, Kase C, Berger K et al. Smoking and Risk of hemorrhagic stroke in women. Stroke

2003;34;2792-2795. 16. Ischemic stroke and combined oral contraceptives: results of an international, multicentre, case control

study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1996;348:498-505.

17. World Health Organization. Hemorrhagic strokes, stroke risk and combined oral contraceptives: results of an international, multicentre, case controlled study: WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet1996;348:505-510.

18. Barnoya J, Glantz S. Cardiovascular effects of second hand smoke. Circulation 2005;11:2628-2698.

19. Zhang X, Shu XO, Yang G, et al. Association of passive smoking by husbands with prevalence of stroke among Chinese women nonsmokers. Am J Epidemiol 2005;161:213-218.

20. Golditz GA, Stamfer B, Willer WC, et al. Cigarette smoking and risk of stroke in middle aged women. N Engl J Med 1988;18:937-941.

21. Tell GS, Polak JF, Ward BJ, et al. Relation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group. Circulation 1994;90:2905-2908.

22. Wannamabee SG, Shaper MC, Smoking cessation and the risk of stroke in middle aged men. JAMA 1998;274:155-160.

23. Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence: Clinical practice guideline. Rockville, Md: US Department of Health and Human Services;2000.

24. Fiore MC, Bailey WC, Cohen SJ, et al. Smoking cessation. Rockville, Md: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research AHCPR Publication;1996.

25. Sacco R, Adams R, Albers G, et al. Guidelines for the Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke 2006; 37:577-617.

XI. EXCESSIVE ALCOHOL

A. Epidemiology: There is a direct, dose-dependent effect of the consumption of alcohol on the risk of hemorrhagic stroke but the association with ischemic stroke varies with different studies.1-4 Most studies suggest a J-shaped association between alcohol and ischemic stroke: a protective effect with light to moderate drinking, and an elevated risk with heavy consumption.5-8 While the protective effect of light consumption alcohol is evident among Caucasians, this is not evident among Asians.2,4-6,9-11 Moderate alcohol consumption decreased risk of ischemic stroke in a multiethnic population.12 Heavy alcohol use, either daily or in binges, is related to excess of stroke risk.13 B. Risk Modification: Alcohol consumption of up to two drinks per day was protective against ischemic strokes in Caucasians, Blacks and Hispanics, but consumption above five drinks per day increased the risk of ischemic stroke.14 C. Recommendations: Moderate intake of alcohol in those who drink alcohol and have no health contraindications to its use. Consumption of alcohol, up to 30 mL (or 28 grams) of ethanol per day, equivalent to 60 mL or two jiggers of 100-proof whiskey, one glass of wine (240 mL) or two bottles of beer (720 mL), or two drinks per day for men and one drink per day for non-pregnant women, may reduce the risk of ischemic stroke (Class IIb-C). Patients with ischemic stroke or TIA who are heavy drinkers should eliminate or reduce their consumption of alcohol (Class I-A). Those who do not customarily drink alcohol should not be encouraged to do so. Bibliography

1. Donahue RP, Abbott RD, Reed DM, Yano K. Alcohol and hemorrhagic stroke. The Honolulu Heart Program. JAMA 1986;255:2311-2314.

2. Tanaka H, Ueda Y, Hayashi M, et al. Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community. Stroke 1982;13:62-73.

3. Tanaka H, Hayaski M, Date C, et al. Epidemiologic studies of stroke in Shibata, a Japanese provincial city: preliminary report on risk factors for cerebral infarction. Stroke 1985;16:773-780.

4. Iso H, Kitamara A, Shimamoto T, et al. Alcohol intake and the risk of cardiovascular disease in middle-aged Japanese men. Stroke 1995;26:767-773.

5. Gill JS, Zezulka AV, Shipley MJ, et al. Stroke and Alcohol consumption. N Engl J Med 1986;315:1041-1046.

6. Djousse L, Ellsion RC, Beiser A, et al. Alcohol consumption and risk of ischemic stroke. The Framingham Study. Stroke 2002;33:907-912.

7. Berger K, Ajani CA, Kase CS, et al. Light-to-moderate alcohol consumption and risk of stroke among US male physicians, N Engl J Med 1999;341:1557-1564.

8. Stampfer MJ, Colditz GA, Willet WC, et al. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med 1988;319:267-273.

9. Camargo CA. Moderate alcohol consumption and stroke. The epidemiologic evidence. Stroke 1989;20:611-1626.

10. Kono S, Ikeda M, Tokudome S, et al. Alcohol and mortality: a cohort study of male Japanese physicians. Int J Epidemiol 1986;15:527-532.

11. Kiyohara Y, Kato I, Iwamoto H, et al. The impact of alcohol and hypertension on stroke incidence in a general Japanese population: The Hisayama Study. Stroke 1995;26:368-372.

12. Elkind MSV, Sciacca R, Boden-Albal B, et al. Moderate alcohol consumption reduces risk of ischemic stroke. The Northern Manhattan Study. Stroke 2006;37:13-19.

13. Kozarerevic D, McGee D, Vojvodic N, et al. Frequency of alcohol consumption and morbidity and mortality. The Yugoslavia Cardiovascular Disease Study. Lancet 1980;1:613-616.

14. Sacco RL, Elkind M, Boden B, et al. The protective effect of moderate alcohol consumption on ischemic stroke. The Northern Manhattan Study. JAMA 1999;281:52-60.

XII. PERIPHERAL ARTERIAL DISEASE Peripheral arterial disease (PAD) is characterized by arterial stenosis and occlusion of the peripheral arterial bed. It can be symptomatic or asymptomatic. Symptomatic PAD ranges from intermittent claudication (IC) to chronic limb ischemia. Regardless of symptomatology, PAD is an indicator of diffuse systemic atherosclerosis. Risk factors include smoking, DM, dyslipidemia, hypertension and hyperhomocysteinemia, which considerably and frequently overlap and coexist with coronary and cerebrovascular disease. There are numerous reports on the increased risk of MI, stroke and cardiovascular death in patients with PAD.1,2

A. Epidemiology: The prevalence of PAD is highly age dependent. Using objective testing with ankle-brachial index (ABI) in a U.S. population showed the prevalence was 2.5% in people aged <60 years old, while among the 60- to 69-year age group the prevalence is 8.3%, and is 18.8% in those >70 years old.3

There is a 20% to 60% increased risk for MI and a two- to six-fold increased risk of death due to coronary artery events in PAD patients.4-8 The risk of stroke is increased by approximately 40%. In the Atherosclerosis Risk in Communities (ARIC) study, men with PAD were four to five times more at risk of stroke and TIA than those without PAD.8

In addition, all-cause mortality rate is 61.8% after 10 years in men with PAD compared with 16.9% in unaffected men.6 The corresponding mortality rates for women were 33.3% and 11.6%, respectively. The increase in total mortality was due to a sharp increase in cardiovascular mortality, which persisted even

after adjusting for pre-existing CAD and cerebrovascular disease at baseline. The risk was proportional to the severity of PAD.

Local studies reported that 2% of Filipinos aged 55 years and older have IC, and approximately 5% have PAD upon ABI confirmation. In a study on Filipino patients aged 40 years or older and confined in the intensive care unit for heart attack, stroke or type 2 DM, 30% had silent PAD.9 The 2003 NNHeS reported a PAD prevalence of 1.6% among Filipinos aged 20 years and above.10

B. Risk Modification: In lower-extremity PAD, adverse cardiovascular events may be reduced with lifetime modification or elimination of risk factors, such as cigarette smoking, diabetes mellitus, dyslipidemia and hypertension. Exercise and a non-atherogenic diet are strongly advised

B1. Smoking Cessation No prospective RCTs have shown the effects of smoking cessation on

cardiovascular events. Only observational studies have shown that the risk of death, MI and limb loss is greater in individuals who continue to smoke than those who stop smoking.11-13

B2. Diabetes Mellitus It is still unclear whether blood glucose control decreases the risk of

adverse cardiovascular events in those with lower-extremity PAD. Analysis of the Diabetes Control and Complication Trial (DCCT) showed that the use of intensive insulin therapy on type 1 DM patients only reduced risk of IC, peripheral revascularization and amputation by 22%, which was not statistically significant.14 The 10-year United Kingdom Prospective Study (UKPDS) showed that aggressive treatment (using sulfonylureas or insulin) in type 2 DM patients reduced the risk of MI by 16% (borderline significance) compared with conventional treatment, but did not reduce the risk of death or stroke.15

B3. Dyslipidemia Treatment of dyslipidemia in patients with systemic atherosclerosis can

reduce future adverse cardiovascular events.16 In the HPS, which included 6,748 PAD patients, there was a 25% reduction of cardiovascular events in the simvastatin-treated group.

B4. Hypertension In PAD patients, antihypertensive treatment may diminish perfusion to the

limb and exacerbate symptoms of limb ischemia. However, most patients do not experience any worsening of symptoms with appropriate antihypertensive therapy needed to reduce risk of cardiovascular events.

The use of beta-blockers has been controversial in the treatment of PAD patients. However, a meta-analysis of 11 placebo-controlled studies in patients with PAD showed that beta-blockers did not adversely affect walking capacity.17

The Heart Outcomes Prevention Evaluation (HOPE), which included 4,051 PAD patients randomized to ramipril or placebo, reported risk reduction for MI,

stroke or vascular death by 25%, similar to that achieved in the overall study population.18 C. Recommendations: Individuals with risk factors for PAD, regardless of whether they are symptomatic and asymptomatic, should be identified and ABI measured. Therapeutic interventions to diminish the increased risk of MI, stroke and death may be given (Class I-B). Treatment used in the management of atherosclerotic conditions, such as CAD and cerebrovascular disease, as recommended in the other sections of these guidelines, may reduce the risk of stroke. Those with PAD who smoke should be advised to quit. Smoking cessation interventions, including behavior modification therapy or nicotine replacement therapy, should be offered (Class I-B). Reducing HbA1c to <7% through tight glycemic control may reduce microvascular complications and improve cardiovascular outcomes (Class IIa-C).

Statins are indicated for all patients with PAD (Class I-B), and treatment should aim to reduce serum cholesterol to < 70mg/dL when at very high risk of ischemic events (Class IIa-B). Treatment with fibric acid derivatives can be useful for PAD patients with low HDL, normal LDL and elevated triglycerides (Class IIa-C).

Antihypertensive treatment should aim to reduce BP to <140/90 mmHg, or <130/80 mmHg for those with DM or chronic renal disease (Class I-A). Beta-blockers are effective and are not contraindicated in PAD patients (Class I-A). It is reasonable to use ACEIs for those with symptomatic PAD to reduce cardiovascular risk (Class IIa-B). ACEIs may be considered for asymptomatic PAD patients to reduce cardiovascular risk (Class IIb-C).

Antiplatelets are indicated to reduce risk of MI, stroke and vascular death in PAD patients (ClassI-A). Daily aspirin 75 to 325 mg is considered safe and effective in reducing the risk of MI, stroke or vascular death (ClassI-A). Clopigrel 75 mg/day is recommended as an alternate to (Class I-B). Oral anticoagulation therapy with warfarin is not indicated to reduce the risk of adverse cardiovascular events in patients with PAD (ClassIII-C). Bibliography

1. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic) [trunc]. Circulation 2006;113:e463-e654.

2. Criqui MH,Denenberg JO, Langer RD, et al. The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med 1997;2:221-226.

3. Meijer WT, Hoes AW, Rutgers D, et al. Peripheral arterial disease in the elderly: The Rotterdam Study. Arterioscler Thromb Vasc Biol 1998;18:185-192.

4. Smith GD, Shipley MJ, Rose G. Intermittent Claudication, heart disease risk factors, and mortality. The Whitehall Study. Circulation 1990;82:1925-1931.

5. Newman AB, Sutton-Tyrrel K, Vogt MT, et al. Morbidity and mortality in hypertensive adults with low ankle/arm blood pressure index. JAMA 1993;270:487-489.

6. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381-386.

7. Vogt MT, Cauley JA, Newman AB, et al. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA 1993;270:465-469.

8. ZhengZj, SharrettAR ,Chambless LE, et al. Associations of ankle/brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 1997;131:115-125.

9. Abola MT, DansA; for the Council of Stroke and Peripheral Vascular Diseases, Philippine Heart Association (PHILPAD Study). Phil J Int Med 2003;41:71-74.

10. Dans AL, Morales DD, Abola TB, Roxas J, et al; for NNHeS 2003 Group. National Nutrition and Health Survey (NNHeS): Atherosclerosis-related Diseases and Risk Factors. Phil J Int Med 2005;43;103-115.

11. Faulkner KW, House AK, Castleden WM. The effect of cessation of smoking on the accumulative survival rates of patients with symptomatic peripheral vascular disease. Med J Aust 1983;1;217-219.

12. Lassila R, Lepantalo M. Cigarette smoking and the outcome after lower limb arterial surgery. Acta Chir Scand 1988;154:635-640.

13. Johnson T, Bergstrom R Cessation of smoking in patients with intermittent claudication: effect on the risk of peripheral vascular complications: myocardial infarction and mortality. Acta Med Scand 1987:221:253-260.

14. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995;75:894-903.

15. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patient with type 2 diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group, Lancet 1998;352:837-853.

16. Heart Study Collaboration Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002;360:7-22.

17. Radack K, Deck C. Beta adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease: a meta-analysis of randomized controlled trials. Arch Intern Med 1996;151:1769-1776.

18. Calligaro KD, Musser DJ, Chen AY, et al. Duplex ultrasonography to diagnose failing arterial prosthetic. Surgery 1996;120:455-459.

XIII. PHYSICAL INACTIVITY A. Epidemiology: Physical inactivity is a growing public health problem that may have a major impact on the prevalence of atherothrombotic cardiovascular disease in the coming decades. The relative risk of cardiovascular disease associated with physical inactivity ranges from 1.5 to 2.4, a risk increase similar to those observed with high blood cholesterol, high BP or cigarette smoking.1 Physical inactivity is a risk factor for stroke, DM, colon and breast cancer, obesity, hypertension, osteoporosis and depression.2-6 Local data shows the odds ratio for stroke associated with physical inactivity is 1.23.7 B. Risk modification

B1. Primary Stroke Prevention Physical activity is defined as any bodily movement produced by skeletal

muscles that result in energy expenditure beyond resting expenditure. Physical activity reduces stroke risk in both genders and across all racial/ethnic and age groups (OR; 0.37).8,9 The Framingham Heart Study, the Honolulu Heart Program, and the Oslo Study have shown the protective effect of physical activity for men.10-12 There seems to be a graded linear relation between the volume of physical inactivity and total stroke.13 The Physicians’ Health Study showed a lower total stroke risk associated with vigorous exercise (five times a week or more) among men (RR; 0.86).14 The Harvard Alumni Study showed a decrease in total stroke risk in men who were highly physically active (RR; 0.82).15

For women, the Nurses’ Health Study and the Copenhagen City Heart Study showed an inverse association between level of physical activity and stroke incidence.16,17 Physical activity (in sports, leisure time or at work) also reduced risk of ischemic strokes, in particular.9,18

The protective effect of physical activity may be partly mediated by BP reduction, improvement of lipid profiles (reduces triglyceride, increases HDL, and decreases LDL:HDL ratios), improvement of glucose homeostasis and insulin sensitivity, and improvement in body composition and weight. 3,4,19 Other benefits of physical activity include reduction in blood coagulability,20-22 improvement of coronary blood flow,23 augmentation of cardiac function, 24 enhancement of endothelial function,25-27 improvement of autonomic tone,28 and reduction of systemic inflammation.29

B2. Secondary Stroke Prevention The cardiac response to acute exercise among stroke survivors has been

documented in some studies. Stroke patients achieve significantly lower maximal workloads, heart rate and BP responses than control subjects during progressive exercise testing to volitional fatigue.30,31 Furthermore, stroke survivors are often deconditioned and predisposed to a sedentary lifestyle that limits performance of activities of daily living, increases the risk for falls, and may contribute to a heightened risk for recurrent stroke and cardiovascular disease. Thus, the major rehabilitation goals for the stroke patient are: (1) to prevent complications of prolonged inactivity; (2) to decrease recurrent stroke and cardiovascular events, and; (3) to increase aerobic fitness.

Stroke patients can increase their cardiovascular health and fitness with regular aerobic exercise.32 In a RCT of 42 hemiparetic stroke survivors, vigorous aerobic exercise training three times per week for 10 weeks significantly improved peak oxygen consumption and workload, submaximal exercise, BP response, exercise time and sensorimotor function.33 In a study of 35 stroke patients with multiple comorbidities who underwent 12 weeks of a 1-hour/day, 3-days/week exercise program of combined cardiovascular, strength and flexibility training, the exercise group had significant gains in peak oxygen uptake, strength and improvements in body composition compared with controls.34 In a RCT involving 88 men with CAD and disability, two-thirds of whom were stroke survivors, a 6-month home exercise training program significantly increased peak

left ventricular ejection fraction and HDL, and decreased resting heart rate and total serum cholesterol.35 C. Recommendations

C1. Primary Stroke Prevention Increased physical activity is associated with a reduction in stroke risk, and is recommended (Class I-B). It is important to recognize that physical education in school may form the starting point for an active lifestyle later in life. At least 30 minutes of moderate-intensity aerobic exercise on most days of the week (preferably all days) is recommended as part of a healthy lifestyle (Class IIa-B). Healthy people should be advised to choose enjoyable activities that fit into their daily routine, preferably for 30 to 45 minutes, four to five times weekly, at an intensity to maintain 60% to 80% of the average maximum heart rate. Additional benefits are gained from vigorous-intensity activity.36

C2. Secondary Stroke Prevention Exercise for stroke patients is recommended and should be tailored to

individual needs and limitations. In general, aerobic training at 40% to 70% of peak oxygen consumption or heart rate reserve may be advised to stroke survivors.37 Continuous or accumulated aerobic training for 20 to 60 minutes daily, three to seven days a week, depending on the patient’s level of fitness, is advised.

Persons with known or suspected cardiovascular, respiratory or neurological disorders should consult a physician before beginning or significantly increasing physical activity. Adaptive programs for post-stroke patients depending on neurological deficits are recommended.38 Bibliography

1. Pate RR, Pratt M, Blair SN, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA 1995;273:402-407.

2. Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med 2004;116:682-692.

3. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ 2006;174:801-809.

4. Warburton DE, Gledhill N, Quinney A. The effects of changes in musculoskeletal fitness on health. Can J Appl Physiol 2001;26:161-216.

5. Warburton DE, Gledhill N, Quinney A. Musculoskeletal fitness and health. Can J Appl Physiol 2001;26:217-237.

6. Shephard RJ. Absolute versus relative intensity of physical activity in a dose-response context. (discussion S419-20). Med Sci Sports Exerc 2001;33:S400-S418.

7. Roxas A; for the Philippine Neurological Association and Department of Health. Risk factors for stroke among Filipinos. Phil J Neur 2002;6:1-7.

8. Thom T, Haase N, Rosamond W, et al. Heart Disease and Stroke Statistics 2006 Update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006;113:e85-e151.

9. Sacco, RL, Gan R, Boden-Albala B, et al. Leisure-time physical activity and ischemic stroke risk: the Northern Manhattan Stroke Study. Stroke 1998;29:380-387.

10. Kiely, DK, Wolf PA, Cupples LA, Beiser AS, Kannel WB. Physical activity and stroke risk: the Framingham Study. Am J Epidemiol 1994;140:608-620.

11. Abbott, RD, Rodriguez BL, Burchfiel CM, Curb JD. Physical activity in older middle-aged men and reduced risk of stroke: the Honolulu Heart Program. Am J Epidemiol 994;139:881-893.

12. Haheim, LL, Holme I, Hjermann I, Leren P. Risk factors of stroke incidence and mortality. A 12-year follow-up of the Oslo Study. Stroke 1993;24:1484-1489.

13. Hu FB, Stampfer MJ, Colditz GA, et al. Physical activity and risk of stroke in women. JAMA 2000;283:2961-2967.

14. Lee IM, Hennekens CH, Berger K, et al. Exercise and risk of stroke in male physicians. Stroke 1999;30:1-6.

15. Lee IM, Paffenbarger RS Jr. Physical activity and stroke incidence: the Harvard Alumni Health Study. Stroke 1998;29:2049-2054.

16. Lindenstrom E, Boysen G, Nyboe J. Lifestyle factors and risk of cerebrovascular disease in women. The Copenhagen City Heart Study. Stroke 1993;24:1468-1472.

17. Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 1991;151:1141-1147.

18. Evenson KR, Rosamond WD, Cai J, et al. Physical activity and ischemic stroke risk: the Atherosclerosis Risk in Communities Study. Stroke 1999;30:1333-1339.

19. American College of Sports Medicine. Position Stand. Physical activity, physical fitness, and hypertension. Med Sci Sports Exerc 1993;25:i-x.

20. Physical activity and cardiovascular health. NIH Consensus Development Panel on Physical Activity and Cardiovascular Health. JAMA 1996;276:241-246.

21. Rauramaa R, Salonen JT, Seppanen K, et al. Inhibition of platelet aggregability by moderate-intensity physical exercise: a randomized clinical trial in overweight men. Circulation 1986;74:939-944.

22. San Jose, C, Apaga N, Florento L, Gan R. Effects of Aerobic Exercise and Training on Coagulation, Platelet Aggregation, and Plasma Lipids. Vasc Dis Prev 2005;2:1-5.

23. Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 2000;342:454-60.

24. Warburton, DE, Haykowsky MJ, Quinney HA, et al. Blood volume expansion and cardiorespiratory function: effects of training modality. Med Sci Sports Exerc 2004;36:991-1000.

25. Gokce N, Vita JA, Bader DS, et al. Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am J Cardiol 2002;90:124-127.

26. Kobayashi N, Tsuruya Y, Iwasawa T, et al. Exercise training in patients with chronic heart failure improves endothelial function predominantly in the trained extremities. Circ J 2003;67:505-510.

27. Hambrecht R, Gielen S, Linke A, et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. JAMA 2000;283:3095-3101.

28. Tiukinhoy S, Beohar N, Hsie M. Improvement in heart rate recovery after cardiac rehabilitation. J Cardiopulm Rehabil 2003;23:84-87.

29. Adamopoulos S, Parissis J, Kroupis C, et al. Physical training reduces peripheral markers of inflammation in patients with chronic heart failure. Eur Heart J 2001;22:791-797.

30. Monga TN, Deforge DA, Williams J, et al. Cardiovascular responses to acute exercise in patients with cerebrovascular accidents. Arch Phys Med Rehabil 1988;69:937-940.

31. King ML, Guarracini M, Lenihan L, et al. Adaptive exercise testing for patients with hemiparesis. J Cardiopulm Rehabil 1989;9:237-242.

32. Gordon, N., Gulanick M, Costa F, et al. Physical activity and exercise recommendations for stroke survivors: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention; the Council on Cardiovascular Nursing; the Council on Nutrition, Physical Activity, and Metabolism; and the Stroke Council. Circulation 2004;109:2031-2041.

33. Potempa K, Lopez M, Braun LT, et al. Physiological outcomes of aerobic exercise training in hemiparetic stroke patients. Stroke 1995;26:101-105.

34. Rimmer JH, Riley B, Creviston T, et al. Exercise training in a predominantly African-American group of stroke survivors. Med Sci Sports Exerc 2000;32:1990-1996.

35. Fletcher BJ, Dunbar SB, Felner JM, et al. Exercise testing and training in physically disabled men with clinical evidence of coronary artery disease. Am J Cardiol 1994;73:170-174.

36. Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 Update. Circulation 2002;106:388-391.

37. Palmer-McLean K, Harbst KB. Stroke and brain injury. In: Durstine JL, Moore GE, eds. ACSM’s Exercise Management for Persons With Chronic Diseases and Disabilities. 2nd ed. Champaign, Ill: Human Kinetics; 2003:238–246.

38. Wolf P, Clagett GP, Easton D et al. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack. A statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke 1999;30:1991-1994.

XIV. OBESITY A. Epidemiology: The World Health Organization defined “overweight” as having a body mass index (BMI) >25 kg/m2 and “obesity” with a BMI >30 kg/m2 for the general population.1 However, the National Institute for Health and Clinical Excellence (NICE) recommends that overweight or obesity among Asian adults should be set at 23 and 27.5kg/m2 respectively.2 Waist circumference (WC) is positively correlated with disease risk, and is one of the most practical measurements for assessing abdominal fat mass (central obesity). For Asians, the cutoff points are 90 cm (35 inches) for males and 80 cm (32 inches) for females.2

Another measure of abdominal fat deposition is the waist-hip ratio (WHR), defined as the waist circumference divided by the hip circumference. Elevated WHR is defined as >0.95 in males and >0.85 in females.3

In the Philippines, the prevalence of obesity based on BMI has increased from 4.6% to 5.0% between 1998 to 2003.4 Obesity is increasingly being recognized as a modifiable risk factor for cardiovascular disease, particularly ischemic heart disease.5 Primary prevention studies documenting the specific impact of obesity on stroke have varied results. In men, findings from the Physicians’ Health Study have shown that an increasing BMI is associated with a steady increase in ischemic stroke, independent of hypertension, diabetes and cholesterol.6 Among women, data are inconsistent, with some studies showing association, while others, none.7,8

Several studies suggest that abdominal obesity, rather than general obesity, is more related to stroke risk.9,10 In the Northern Manhattan Study, a significant and independent association between abdominal obesity (elevated WHR) and ischemic stroke was found in all racial/ethnic groups, whereas BMI did not show any significant association with ischemic stroke.9 Furthermore, persons with elevated BMI or WHR have increased carotid artery intima-media thickness and cross-sectional intima-media area, which are two preclinical predictors of atherosclerosis.11

B. Risk Factor Modification

B1. Primary Stroke Prevention Epidemiological studies indicate that increased body weight and

abdominal fat are directly associated with stroke risk. Weight reduction is recommended because it lowers BP (Class I-A) and may thereby reduce the risk of stroke. Modest weight loss (e.g., 10% of the initial body weight over 6 months) is realistic and attainable.12 It is better to maintain a moderate loss over the long term than to achieve a greater weight loss that cannot be maintained.

B2. Secondary Stroke Prevention

Although no study has demonstrated that weight reduction will reduce stroke recurrence in patients who have suffered a previous stroke or TIA, losing weight significantly improves BP, fasting glucose values, serum lipids and physical endurance.13 Because obesity is a contributing factor to other risk factors associated with recurrent stroke, promoting weight loss and maintenance of a healthy weight is important. Exercise and a diet rich in fruits and vegetables can help control weight and reduce the risk of stroke, MI and death.14,15

C. Recommendation: Weight reduction should be considered for all overweight patients to maintain the following goals: BMI=18.5 to 22.9 kg/m2; WHR<0.95 in males and <0.85 in females; and WC<90 cm (35 inches) in males and <80 cm (32 inches) in females.16 Gradual and moderate weight loss is encouraged for overweight and obese patients. Clinicians should encourage weight management as early as childhood through an appropriate balance of caloric intake, physical activity, exercise and behavioral counseling. Table 7. Weight classifications and associated comorbidities risk according to BMI and waist circumference in adult Asians16

Classification BMI (kg/m2) Risk of comorbidities

Waist circumference

<90 cm (men) <80 cm (women)

≥90 cm (men) ≥80 cm (women)

Underweight

<18.5 Low* Average

Normal range 18.5-22.9 Average Increased

Overweight (at risk)

23-24.9 Increased Moderate

Obese I 25-29.9 Moderate Severe

Obese II ≥30 Severe Very severe

* But increased risk of other clinical problems

Bibliography

1. World Health Organization. Obesity: Preventing and managing the global epidemic. Report of a WHO Consultation. WHO Technical Report Series 894(3), i-253. Geneva: WHO; 2000.

2. National Institute for Health and Clinical Excellence. Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children. NICE guideline: first draft for consultation, March 2006. London: NICE; 2006.

3. Sproston K, Primatesta P, eds. Health Survey for England 2002: volume 1: the health of children and young people, London: The Stationery Office;2003.

4. Dans AL, Morales DD, Abola TB, Roxas J, et al; for NNHeS 2003 Group. National Nutrition and Health Survey (NNHeS): Atherosclerosis-related Diseases and Risk Factors. Phil J Int Med 2005;43;103-115.

5. Grundy SM, Balady GJ, Criqui MH, et al. Primary prevention of coronary heart disease: guidance from Framingham : a statement for healthcare professionals from the AHA Task Force on Risk Reduction. American Heart Association. Circulation 1998;97:1876-1887.

6. Kurth T, Gaziano JM, Berger K, Kase CS,Rexrode KM, Cook NR,Buring JE. Body mass index and the risk of stroke in men. Arch Intern Med. 2002; 162:2557-2562.

7. Rexrode KM, Hennekens CH, Willeu WC,et al. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA 1997:277;1539-1545.

8. Lindenstorm E, Boysen G, Nyboe J. Lifestyle factors and risk of cerebrovascular disease in women: Copenhagen City Heart Study. Stroke 1993:24;1468-1472.

9. Suk SH, Sacco RL, Boden-Albala B, et al; for the Northern Manhattan Stroke Study. Stroke 2003;34;1586-1592.

10. Dey DK, Rothenberg E, Sundh V, et al. Waist circumference, body mass index, and risk for stroke in older people: a 15 year longitudinal population study of 70-year olds. J Am Geriatr Soc 2002:50;1510-1518.

11. De Michelle M, Panico S, Iannuzzi A, et al. Association of obesity and central fat distribution with carotid artery wall thickening in middle-aged women. Stroke 2002;33:2293.

12. Singapore Ministry of Health (MOH). Obesity. Singapore Ministry of Health – National Government Agency. 2004.

13. Anderson JW, Konz Ec. Obesity and disease management: effects of weight loss on comorbid conditions. Obes Res 2001:9 (Suppl 4);326S-334S.

14. Renaud S, Lorgeril M., Delaye J, et al. Cretan Mediteranean diet for prevention of coronary heart disease. Am J Clin Nutr 1995:61 (Suppl):1360S-1367S.

15. Singh RB, Dubnov G, Niaz MA, et al. Effect of an Indo-Mediterranean diet in progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study: a randomized single-blind trial). Lancet 2002:360:1455-1461.

16. Regional Office for the Western Pacific of the World Health Organization, the International Association for the Study of Obesity and the International Obesity Task Force. The Asia-Pacific perspective: Redefining obesity and its treatment. Health Communications Australia Pty. Limited, February 2000.

XV. DIET

A. Epidemiology: Although dietary factors may be risk factors for stroke, their role is poorly defined. Homocysteine may be associated with stroke and is associated with deficiency of dietary intake of folate, vitamins B6 and B12 (observed in case-control studies but not clearly in prospective studies).1 In ecological and some prospective studies, a higher level of sodium intake is associated with an increased risk of stroke.2-5 Higher potassium intake is also associated with reduced stroke risk in prospective studies.6,7 However, several methodological limitations, particularly difficulties in estimating dietary electrolyte intake, hinder risk assessment and may lead to false-negative results in observational studies. B. Risk Modification: Prospective studies show that increased fruit and vegetable consumption is associated with a dose-related reduced stroke risk. Fruits and vegetables may contribute to stroke prevention though antioxidant mechanisms or elevation of potassium levels.7-10 Increase sodium intake is associated with hypertension, and reduction in salt consumption may significantly lower BP and reduce stroke mortality. The 2006 AHA Guidelines recommend a well-balanced diet containing ≥5 servings of fruits and vegetables per day to reduce stroke risk. The DASH diet, which emphasizes fruit, vegetables and low-fat dairy products and is reduced in saturated and total fat, also lowers BP and is recommended (Class I- A).11

C. Recommendations: While awaiting more definitive data, reducing intake of sodium and increasing intake of potassium to help lower BP is recommended (Class I-A). The recommended sodium intake is ≤2.3 g/day (100 mmol/day), and the recommended potassium intake is ≥ 4.7 g/day (120 mmol/day).

It seems prudent to limit excess saturated fat and to replace vitamins B6 and B12 and folate when such deficiencies are identified

A diet rich in fruits and vegetable is advised (Class IIb-C). Bibliography:

1. Selhub J, Jacques PF, Bostom AG, et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. NEJM 1995;332:286-291.

2. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995;247:1049-1057.

3. Perry IJ, Beevers DG. Salt intake and stroke: a possible direct effect. J Hum Hypertens 1992;6:23-25.

4. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA 1999;282:2027-2034.

5. Nagata C, Takatsuka N, Shimizu N, Shimizu H. Sodium intake and risk of death from stroke in Japanese men and women. Stroke 2004;35:1543-1547.

6. Joshipura KJ, Ascherio A, Manson JE, et al. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 1999;282:1233-1239.

7. Khaw KT, Barrett-Connor E. Dietary potassium and stroke-associated mortality. A 12-year prospective population study. N Engl J Med 1987;316:235-240.

8. Ascherio A, Rimm EB, Hernan MA, et al. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation 1998;98:1198-1204.

9. Gillman MW, Cupples LA, Gagnon D et al. protective effect of fruits and vegetables on development of stroke in men. JAMA 1995;273:1113-1117.

10. Khaw KT, Barret-Connor E. Dietary potassium and stroke associated mortality: A 12-year prospective population study. NEJM 1987;316:235-240.

11. Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council. Stroke 2006;37:1583-1633.

APPENDIX OF DIET MODIFICATION FOR STROKE PREVENTION The FNRI-DOST and the Nutritionists-Dietitians Association of the Philippines (NDAP) provide a simple diet guide that clinicians can in advising patients on dietary fat modification. However, patients requiring intensive dietary interventions for whatever reason or condition should be referred to a nutritionist/dietitian for individualized counseling.

Simple Dietary Plan for Fat Modification (2000)

The Biomedical Nutrition Research Division, FNRI-DOST, and NDAP Some pointers to observe in planning meals:

1. Choose freely from fruits, vegetables, cereals, root crops, bread, dried beans and nuts.

2. Eat fish as main dish at least three times a week. 3. May eat chicken meat as a substitute to fish at least three to four times a

week.

4. For other kinds of meat, use lean parts and prepare as boiled, baked, broiled, or roasted. Trim off any visible fat.

5. Use evaporated filled milk or skimmed milk instead of whole milk and avoid whole milk products such as cheese, butter, cream, etc. Use margarine made with allowed vegetable oil.

6. Use unsaturated fats and oils such as corn oil, soybean oil, peanut butter, etc.

7. Limit eggs to only three per week. 8. Avoid rich desserts such as cakes, pastries, cookies, pies, ice cream and

chocolates. 9. Always read the nutrition labels of packaged/processed foods.

Food selection guide

Food group Allowed Restricted/avoided

Fats and oils In prescribed amounts: Olive, canola, corn,

soybean, palm, sunflower and peanut oils. Coconut oil.

Fats and oils from animal foods, butter. Hydrogenated vegetable oils (e.g., margarine, lard, shortening, spread)

Meat and chicken fat drippings used for sauces, bacon fat, “chicharon”

Meat, fish, poultry, eggs, milk, dry beans

Eat frequently*: Fish (fresh, frozen or canned in

water, tomato or vinegar); chicken breast without skin or fat. Dried beans, lentils, fresh or frozen sweetpeas; “vege-meat”, tokwa, taho, tofu & other bean products;

Eat occasionally**: Very lean, well-trimmed cuts

of beef, pork, veal, lamb; crabmeat, shrimp without head; whole eggs up to 3 pieces per week, eggwhite as desired, may be cooked in allowed fat; Skimmed milk or low fat milk or cheese

Fish roe, crabfat “aligui” shrimp head, oyster, clams.

Fatty meats: cold cuts, canned or frozen meats, sausages.; fatty poultry with skin; internal organs (liver, kidney, heart, tripe, sweetbreads)

Whole milk/cow’s milk and cheese made from whole milk

Vegetable All vegetables prepared without fat or with allowed fats only.

Eat frequently*: Green leafy and yellow vegetables (they are good sources of beta-carotene, vitamin C, calcium, iron and dietary fiber among others)

Buttered, creamed, fried vegetables in restricted fats or cooked with fatty meat and sauces.

Fruit All fruits; adjust fat allowance when using avocado.

Eat frequently*: Vitamin C-rich fruits and deep colored fruits

Avocado in moderation (due to its high fat content)

Rice, corn, rootcrops, noodles, bread and cereals

All cereals, roots/tubers, certain noodles/pasta, wheat bread, “pan de sal” except those restricted

Eat frequently*: Oatmeal, cold cereals, corn and sweet potato

Croissants, muffins, crackers, biscuits, waffles, pancakes, doughnut, rolls made with whole egg, butter, margarine or fat of unknown composition

Fresh mami or miki noodles

Potato chips, french fries, popcorn

Desserts Fat-free/low-fat/light dessert. Fresh or canned fruits in light syrup only. Plain cakes with no icing (angel or sponge cakes), meringue, yogurt, sherbet

Rich dessert especially those made with cream, butter, solid shortening, lard, whole egg, chocolate cookies and pies made from cream fudge, ice cream; pastillas from whole milk, yema

Soups Fat-free broths made from meat or chicken stock. Soups prepared with skimmed/low-fat milk.

Cream soups, fatty broth or stock

Beverage Coffee (not more than 3 cups black), decaffeinated coffee, tea, carbonated beverages in moderation.

Alcoholic drinks: not more than 1 jigger for women and not more than 2 jiggers for men

Soda fountain beverages such as milk shake, malted milk and chocolate drinks.

Alcoholic drinks in moderation.

Miscellaneous Nuts (peanuts, walnut, almond, cashew, pili, etc.) preferably boiled, roasted/baked, consume in moderation.

Nondairy cream in moderation

Spices and seasonings in moderation. Sauce made with allowed fats and skimmed milk, vinegar, pickles, mustard, catsup, banana sauce.

Sauces and gravies with restricted fats or milk; regular mayonnaise

Butter-dipped foods.

Packed dinners or “instant foods” of unknown fat content.

*Eat frequently – at least 4 to 5 times a week. **Eat occasionally – at most, once a month.

APPENDIX TO STROKE PREVENTION

Independent Risk Factors for Stroke Among Filipinos (RIFASAF data)

Statistical model derived using multiple regression analysis (Strata v. 5.0) The odds ratio estimates the risk of a patient for stroke if the variable (risk factor) is resent compare with a similar person without the risk factor. Reference: Roxas A, for the Philippine Neurological Association and Department of Health. Risk factors for stroke among Filipinos. Phil J Neurol 2002;6:1-7. Philippine Prevalence for Atherosclerosis Risk Factors (>20 years old) (2003 National Nutrition Health Survey)

Risk Factor Basis Prevalence (%)

Hypertension BP or history 17.4

Diabetes FBS >125 mg/dL or history or use of anti-diabetes medication

4.6

Stroke History 1.4

Hypercholesterolemia TC ≥240 mg/dL 8.5

Current Smoking (M/F) History 56.3 / 12.1

Obesity: BMI BMI ≥30 4.8

Obesity: Waist Hip Ratio (M/F) 1.0 for men; 0.85 for women

12.1 / 54.8

Angina Pectoris History or questionnaire

12.1

Peripheral Arterial Disease Questionnaire or ankle-brachial index

8.9

Reference: Dans AL, Morales DD, Abola TB, Roxas J, et al; for NNHeS 2003 Group. National Nutrition and Health Survey (NNHeS): Atherosclerosis-related Diseases and Risk Factors. Phil J Int Med 2005;43;103-115.

Variable Odds Ratio 95% Confidence Interval

P-Value

Hypertension 6.01 4.48-8.05 0.000

Diabetes 1.60 1.10-2.32 0.014

Atrial Fibrillation 1.91 0.51-7.19 0.337

Myocardial Infarction

4.67 1.18-18.52 0.029

Rheumatic Heart Disease

3.69 1.05-12.99 0.042

Smoking 1.36 1.00-1.86 0.053

Snoring 3.37 2.49-4.58 0.000

Stress 1.69 1.25-2.29 0.001

Frequent Alcohol Intake

1.75 1.14-2.70 0.011

Guidelines for ACUTE STROKE TREATMENT

ACUTE STROKE TREATMENT Definition of “stroke” Sudden onset of focal neurological deficit lasting more than 24 hours due to an

underlying vascular pathology

Table 8: Definition of stroke severity

TIA and MILD STROKE MODERATE STROKE SEVERE STROKE

TIA: Deficits resolve within 24 hours but usually lasts less than 1 hour without evidence of acute infarction on neuroimaging

or

Alert patients with any of the following:

Mild pure motor weakness of one side of the body, defined as: can raise arm above shoulder, has clumsy hand, or can ambulate without assistance

Pure sensory deficit Slurred but intelligible

speech Vertigo with

incoordination (e.g., gait disturbance, unsteadiness or clumsy hand)

Visual field defects alone Combination of (a) and (b)

Awake patient with significant motor and/or sensory and/or language and/or visual deficit

or Disoriented, drowsy or stuporous patient, but with purposeful response to painful stimuli

Comatose patient with non-purposeful response, decorticate, or decerebrate posturing to painful stimuli

or Comatose patient with no response to painful stimuli

See Guidelines for TIA and Mild Stroke

See Guidelines for Moderate Stroke

See Guidelines for Severe Stroke

GUIDELINES FOR TIA AND MILD STROKE

Management Priorities

Ascertain clinical diagnosis of stroke or TIA (history and physical exam are very important)

Exclude common stroke mimickers (Appendix I) Provide basic emergent supportive care (ABCs of resuscitation) Monitor neuro-vital signs, BP, MAP, RR, temperature, pupils Perform stroke scales (NIHSS, GCS) (Appendix II) Monitor and manage BP; treat if SBP>220 or DBP>120 or MAP>130 (Appendix III). Precautions:

Avoid precipitous drop in BP (BP not >20% of baseline MAP) (Appendix III). Do not use rapid-acting sublingual agents; when needed, use easily titratable IV or oral antihypertensive medication

Ensure appropriate hydration. If IVF is needed, use 0.9% NaCl

Emergent Diagnostics

Complete blood count (CBC)

Blood sugar (CBG, HGT or RBS)

Electrocardiogram (ECG)

PT/PTT

Plain CT scan of the brain as soon as possible; computation of hematoma volume (Appendix IV)

Early Specific Treatment

Ischemic Hemorrhagic

Non-cardioembolic (Thrombotic, Lacunar)

Cardioembolic (Appendix V)

CT Scan Confirmed

(Appendix V)

Aspirin 160-325 mg/day start as early as possible and continue for 14 days (for secondary prevention, see under “Delayed Management and Treatment”)

Neuroprotection (Appendix V-D)

Early rehabilitation once stable within 72 hours

Consider anticoagulation with IV heparin or SQ low molecular-weight heparin (LMWH) (Appendix VI)

or

Aspirin 160-325 mg/day (if anticoagulation is not possible or contraindicated)

Neuroprotection (Appendix V-D) Early rehabilitation once stable within 72 hours

If infective endocarditis is suspected, give antibiotics and do not anticoagulate

Early neurology and/ or neurosurgeon consult for all ICH is recommended

Monitor and maintain BP: MAP 110-130 mmHg (lower limit preferred) (Appendix III)

Neuroprotection (Appendix V-D)

Early rehabilitation once stable within 72 hours Give anticonvulsants only if with seizures Steroids are not recommended Monitor and correct metabolic parameters Correct coagulation / bleeding abnormalities Follow recommendations for neurosurgical intervention (Appendix VII) For aneurysmal SAH, refer to next chapter.

TIA

Aspirin 160-325 mg/day If crescendo TIA (multiple events within hours, increasing severity and duration of deficits), consider anticoagulation with IV heparin or SQ LMWH

CT Scan Not Available

No specific emergent drug treatment recommended Neuroprotection (Appendix V-D) Consult a neurologist or neurosurgeon Early supportive rehabilitation

Place of Treatment

Admit to Hospital (Stroke Unit)

Urgent Outpatient Work-up

1. Stroke onset within 48 hours 2. Patients requiring any specific

active intervention, such as: BP control, monitoring and

stabilization Cardiac stabilization, including AF,

CHF, acute MI Hydration Anticoagulation, if cardioembolic

3. Rapidly worsening deficits 4. Recurrent TIA within the past 2

weeks, especially those with increasing severity and duration of deficits, cardiac arrhythmia, or carotid bruit

1. Single TIA more than 2 weeks 2. Transient monocular

blindness alone 3. Stable mild strokes >48 hours

from ictus not requiring specific active intervention

Advise immediate re-consult or admission if there is worsening of deficit

Delayed Management

Ischemic Hemorrhagic

Thrombotic/Lacunar Cardioembolic

and Treatment (Secondary Prevention)

Control of risk factors Antiplatelets (aspirin, ticlopidine, dipyridamole, extended-release dipyridamole + aspirin combination, clopidogrel, cilostazol) (Appendix VIII)

Carotid ultrasound: If this reveals >70% stenosis, refer to neurologist/neurosurgeon/vascular surgeon for decision-making regarding CEA or stenting

Recommend transcranial Doppler (TCD) to document intracranial stenosis

Echocardiography and/or cardiology consult

If age <75 and PT/INR available, anticoagulation with coumadin

(target INR: 2-3) If age >75, aspirin 80-325 mg/day or coumadin (target INR: 2.0 [1.6 – 2.5])

Long-term strict BP control and monitoring Consider angiogram if age <45 years, normotensive, no clear cause of ICH, and/or is a candidate for surgery

GUIDELINES FOR MODERATE STROKE

Management Priorities

Ascertain clinical diagnosis of stroke (history and physical exam are very important)

Exclude common stroke mimickers (Appendix I) Basic emergent supportive care (ABCs of resuscitation) Neuro-vital signs, BP, MAP, RR, temperature, pupils Perform stroke scales (NIHSS, GCS) (Appendix II) Monitor and manage BP; treat if SBP>220 or DBP>120 or MAP>130

(Appendix III). Precaution: Avoid precipitous drop in BP (not >20% of baseline MAP)

(Appendix III). Do not use rapid-acting sublingual agents; when needed use easily titratable IV or oral antihypertensive medication.

Identify comorbidities (cardiac disease, diabetes, liver disease, gastric ulcer, etc.) Recognize and treat early signs and symptoms of increased ICP (Appendix IX) Ensure appropriate hydration. If IVF is needed, use 0.9% NaCl

Emergent Diagnostics

CBC

CBG, HGT or RBS

PT/PTT

Serum Na+ and K+

ECG Plain CT scan of brain as soon as possible; computation of hematoma volume (Appendix IV)

Early Specific Treatment

Ischemic Hemorrhagic

Non-cardioembolic (Thrombotic, Lacunar)

Cardioembolic (Appendix V)

CT scan confirmed

(Appendix V)

If within 3 hours of stroke onset, consider IV recombinant tissue plasminogen activator (rtPA) and refer to specialist

If within 6 hours of stroke onset and in specialized centers, consider intra-arterial (IA) thrombolysis

Aspirin 160-325 mg/day, start as early as possible

Neuroprotection (Appendix V-D)

Early supportive rehabilitation

If within 3 hours of stroke onset, consider IV rtPA and refer to specialist

If within 6 hours of stroke onset and in specialized centers, consider IA thrombolysis

Aspirin 160-325 mg/day, start as early as possible

If source of embolism can be demonstrated, consider early anticoagulation

Neuroprotection (Appendix V-D)

Early supportive rehabilitation

If infective endocarditis is suspected, give antibiotics and do not anticoagulate

Early neurology and/ or neurosurgical consult for all ICH is recommended

Monitor and maintain BP: MAP 110-130 mmHg (lower limit preferred)

Neuroprotection (Appendix V-D)

Give anticonvulsants only if with seizures Steroids are not recommended Monitor and correct metabolic parameters Correct coagulation/bleeding abnormalities Follow recommendations for neurosurgical intervention (Appendix VII) Early rehabilitation once stable For aneurysmal SAH, refer to next chapter.

CT scan not available

Likely Ischemic Likely Hemorrhagic

No specific emergent drug treatment recommended

Neuroprotection (Appendix V-D) Refer to neurologist Early supportive rehabilitation

Refer to neurologist/neurosurgeon for further diagnostic work-ups and/or subsequent surgery

Neuroprotection (Appendix V-D) Early supportive rehabilitation

Place of Treatment

Hospital – Intensive Care Unit or Stroke Unit

Delayed Management and Treatment (Secondary Prevention)

Ischemic Hemorrhagic

Thrombotic/Lacunar Cardioembolic

Control of risk factors Antiplatelets (aspirin, ticlopidine, dipyridamole, extended-release dipyridamole + aspirin combination, clopidogrel, cilostazol) (Appendix VIII)

Carotid ultrasound: If this reveals >70% stenosis, refer to neurologist/neurosurgeon/vascular surgeon for decision-making regarding CEA or stenting

Recommend TCD to document intracranial stenosis

Echocardiography and/or cardiology consult

INR 2.0 (1.6 – 2.5) If age <75 and PT/INR available, anticoagulation with coumadin

(target INR: 2-3) If age >75, aspirin 80-325 mg/day or coumadin (target INR: 2.0 [1.6 – 2.5])

Long-term strict BP control and monitoring

Consider CT angiography, MRA, or 4-vessel angiography in suspected cases of aneurysm, AV malformation or vasculitis

GUIDELINES FOR SEVERE STROKE

Management Priorities

Ascertain clinical diagnosis of stroke (history and physical exam are very important)

Exclude common stroke mimickers (Appendix I) Basic emergent supportive care (ABCs of resuscitation) Neuro-vital signs, BP, MAP, RR, temperature, pupils Perform stroke scales (NIHSS, GCS) (Appendix II) Monitor and manage BP; treat if SBP>220 or DBP>120 or MAP>130

(Appendix III). Precautions:

Avoid precipitous drop in BP (not >20% of baseline MAP) (Appendix III). Do not use rapid-acting sublingual agents; when needed, use easily titratable IV or oral antihypertensive medication (Appendix IIIB)

Identify comorbidities (cardiac disease, diabetes, liver disease, gastric ulcer, etc.) Recognize and treat early signs and symptoms of increased ICP (Appendix IX) Ensure appropriate hydration. If IVF is needed, use 0.9% NaCl

Emergent Diagnostics

CBC

CBG, HGT or RBS

PT/PTT

Serum Na+ and K+

ECG Plain CT scan of brain; computation of hematoma volume (Appendix IV)

Early Specific Treatment

Ischemic Hemorrhagic

Non-cardioembolic (Thrombotic)

Cardioembolic (Appendix V)

CT scan confirmed

(Appendix V)

May give aspirin 160-325 mg/day

In posterior circulation strokes within 6 hour of onset, consider IA thrombolysis and refer to specialist

Neuroprotection (Appendix V-D)

If cerebellar infarct, consult neurosurgeon as soon as possible

Early supportive rehabilitation

May give aspirin 160-325 mg/day

In posterior circulation strokes within 6 hours of onset, consider IA thrombolysis and refer to specialist

Neuroprotection (Appendix V-D )

If cerebellar infarct, consult neurosurgeon as soon as possible

Early supportive rehabilitation

Supportive treatment: 1. Mannitol 20% 0.5 -

1 g/kgBW q 4-6 hours for 3-7 days

2. Neuroprotection

(Appendix V-D) Neurosurgery consult if: Patient not herniated;

bleed located in putamen, pallidum, cerebellum; family is willing to accept consequences of irreversible coma or persistent vegetative state and goal is reduction of mortality

(Appendix VII) 2. ICP monitoring is contemplated and salvage surgery is considered

Early supportive rehabilitation

CT scan not available

No specific emergent drug treatment recommended Neuroprotection (appendix V-D) Refer to neurologist

Place of Treatment

Intensive Care Unit

Delayed Management and Treatment

Discuss prognosis with relatives of the patient in most compassionate manner

Ischemic Hemorrhagic

Thrombotic Cardioembolic

(Secondary Prevention)

Control of risk factors Antiplatelets (Aspirin, ticlopidine, dipyridamole, extended-release dipyridamole + aspirin combination,

clopidogrel or cilostazol)

(Appendix VIII)

Echocardiography and/or cardiology consult

If age <75 and PT/INR available, anticoagulation with coumadin (target INR=2.0-3.0)

If age >75, aspirin 80- 325 mg/day or coumadin with target INR 2.0 (1.6-2.5)

Long-term strict BP control and monitoring

Consider CT angiography, MRA, or 4-vessel angiography in suspected cases of aneurysm, AV malformation or vasculitis

APPENDIX I

Differential Diagnoses of Stroke A. The presence of any of the following should alert the physician to

consider conditions other than stroke: - Gradual progressive course and insidious onset - Pure hemifacial weakness including forehead (Bell’s palsy) - Trauma - Fever prior to onset of symptoms - Recurrent seizures - Weakness with atrophy - Recurrent headaches (migraine, tension-type headache) B. Conditions that mimic stroke in the emergency department (according

to decreasing frequency): 1. Seizures 2. Systemic infection 3. Brain tumor 4. Toxic-metabolic 5. Positional vertigo 6. Cardiac 7. Syncope 8. Trauma 9. Subdural hematoma 10. Herpes encephalitis 11. Transient global amnesia 12. Dementia 13. Demyelinating disease 14. Cervical spine fracture 15. Myasthenia gravis 16. Parkinsonism 17. Hypertensive encephalopathy 18. Conversion disorder Bibliography Hand P, Kwan J, Lindley R, et al. Distinguishing a stroke and mimic at the bedside. Stroke 2006;37:769 – 775. Libman RB, Wirkowski E, Alvir J, Rao H. Conditions that mimic stroke in the emergency department. Arch Neurol 1995;52:1119-1122. The Brain Matters Stroke Initiative. Acute Stroke Management Workshop Syllabus. Basic Principles of Modern Management for Acute Stroke.

APPENDIX II

Stroke Scales I. Glasgow Coma Scale

Category Score

Eye Opening Spontaneous To speech To pain None

4 3 2 1

Best Motor Response Obeys Localizes Withdraws Abnormal flexion (decorticate) Abnormal extension (decerebrate) None

6 5 4 3 2 1

Best Verbal response Oriented Confused Inappropriate words Incomprehensible sounds None

5 4 3 2 1

Total score=15 II. National Institutes of Health (NIH) Stroke Scale

Items Scale Definition

Ia. Level of Consciousness (LOC)

0 = Alert, keenly responsive 1 = Not alert, but arousable by minor stimulation to obey, answer or respond 2 = Not alert, requires repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (not stereotyped) 3 = Responds only with reflex motor or autonomic effects or totally unresponsive, or totally unresponsive, flaccid, areflexic

Ib. LOC Questions

0 = Answers both questions correctly 1 = Answers one question correctly 2 = Answers neither question correctly

Ic. LOC Commands

0 = Performs both tasks correctly 1 = Performs one task correctly 2 = Performs neither task correctly

2. Best gaze 0 = Normal 1= Partial gaze palsy. Gaze is abnormal in one or both eyes but forced deviation or total gaze paresis is not present 2 = Forced deviation, or total gaze paresis is not overcome by oculocephalic maneuver

3. Visual 0 = No visual loss 1 = Partial hemianopia 2 = Complete hemianopia 3 = Bilateral hemianopia (blind, including cortical blindness)

4. Facial palsy 0 = Normal symmetrical movement 1 = Minor paralysis (flattened nasolabial fold, asymmetry on smiling)

5. Motor (Arm) 5 a. Left arm 5 b. Right arm

0 = No drift; limb holds 90 (or 45) degrees for full 10 seconds 1 = Drifts; limb holds 90 (or 45) degrees but drifts down before full 10 seconds; does not hit bed or other support 2 = Some effort against gravity, limb cannot get up to or maintain (if cued) 90 (or 45) degrees; drifts down to bed, but has some effort against gravity 3 = No effort against gravity; limb falls 4 = No movement 9 = Amputation or joint fusion; explain

6. Motor (Leg) 6 a. Right leg 6 b. Left leg

0 = No drift; leg holds 30-degree position for full 5 seconds 1 = Driftd; leg falls by the end of the 5-second period but does not hit bed 2 = Some effort against gravity; leg falls to bed by 5 seconds but has some effort against gravity 3 = No effort against gravity; leg falls to bed immediately 4 = No movement 9 = Amputation or joint fusion; explain

7. Limb ataxia 0 = absent 1 = Present in one limb 2 = Present in two limbs 9 = Amputation or joint fusion; explain

8. Sensory 0 = Normal; no sensory loss 1 = Mild to moderate sensory loss; patient feels pinprick is less sharp or dull on the affected side; or there is a loss of superficial pain with pinprick, but patient is aware he/she is being touched 2 = Severe or total sensory loss; patient is not aware of being touched in the face, arm or leg

9. Best Language

0 = No aphasia 1 = Mild to moderate aphasia; some obvious loss of fluency or facility of comprehension, without significant limitation on ideas expressed or form of expression. Reduction of speech and/or comprehension, however, makes conversation on provided material difficult 2 = Severe aphasia; all communication is through fragmentary expression; great need for inference, questioning and guessing by the listener. Range of information that can be exchanged is limited; listener carries the burden of communication 3 = Mute, global aphasia; no usable speech or auditory comprehension

10. Dysarthria 0 = Normal 1 = Mild to moderate; patient slurs at least some words and at worst, can be understood with some difficulty 2 = Severe; patient’s speech is so slurred as to be unintelligible in the absence of or out of proportion to any dysphasia, or is mute/anarthric 9 = intubated or other physical barrier; explain

11. Extinction & Inattention

0 = No abnormality 1 = Visual, tactile, auditory, spatial or personal inattention or extinction to bilateral simultaneous stimulation in one of the sensory modalities 2 = Profound hemiattention or hemi-inattention to more than one modality. Does not recognize own hand or orients to only one side of space

Total score=42 III. Modified Rankin Scale

Score

No symptoms at all 0

No significant disability despite symptoms; able to carry out all usual duties and activities

1

Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance

2

Moderate disability; requiring some help but able to walk without assistance

3

Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance

4

Severe disability; bedridden, incontinent and requiring constant nursing care and attention

5

Bibliography

Brott T, Adams H. Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20:864-870. Goldstein LB, Bartels C. Davis JN. Interrater reliability of the NIH Stroke Scale. Arch Neurol 1989;46:660-662. Rankin J. Cerebral vascular accidents in patients over the age of 60. Scot Med J 1957;2:200-215. Van Swieten JC, Koudstaal JP, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604-607. The Brain Matters Stroke Initiative. Acute Stroke Management Workshop Syllabus. Basic Principles of Modern Management for Acute Stroke.

APPENDIX III

Blood Pressure Management A. BP management in Acute Ischemic Stroke

1. Use the following definitions:

Cerebral Perfusion Pressure (CPP) = MAP – ICP MAP = 2 (diastolic) + systolic 3

2. Check if patient is in any condition that may increase BP such as pain, stress, bladder distention or constipation, which should be addressed accordingly. 3. Allow “permissive hypertension” during the first week to ensure adequate CPP but ascertain cardiac and renal protection

a. Treat if SBP>220 or DBP>120 or MAP>130 b. Defer emergency BP therapy if MAP is within 110-130 or SBP=185-220

mmHg or DBP=105-120 mmHg, unless in the presence of: Acute MI Congestive heart failure Aortic dissection Acute pulmonary edema Acute renal failure Hypertensive encephalopathy

4. Treat with small doses of IV antihypertensives patients who are potential candidates for rtPA therapy who have persistent elevations in SBP >185 mmHg or DBP >110 mmHg. Maintain BP just below these limits. 5. Use the following locally available intravenous anti-hypertensives in acute stroke:

Drug Dose Onset of Action

Duration of

Action

Availability/Dilution

Stability Adverse Reactions

Action

Nic

ard

ipin

e

1-15 mg/hour

5-10 mins

1-4 hours

(10 mg/ 10 ml amp ); 10 mg in 90 ml NSS/D5W

1 to 4 hours

Tachycardia, headache, flushing, dizziness, somnolence, nausea

Inhibits calcium ion from entering slow channel, producing coronary, vascular, smooth muscle relaxation & vasodilatation

Hyd

rala

zin

e

IV push 10-20 mg/dose q 4-6 hours as needed, may increase to 40 mg/dose

10-20 mins

3-8 hours

25 mg/mL amp; 25 mg/tab

4 days Tachycardia, flushing, headache, vomiting, increased angina

Direct vasodilatation of arterioles & decreased systemic resistance

La

be

talo

l

5 mg IV push over 2 mins, repeat with incremental dose of 10, 20, 40, 80 mg until desired BP is achieved or a total dose of 300 mg has been administered

2-5 mins

2-4 hours

5 mg/ml in 40 ml vial; 250 mg in 250 mL NSS/D5W

72 hours

Orthostatic hypotension, drowsiness, dizziness, lightheadedness, dyspnea, wheezing & bronchospasm

Alpha- & beta- blocker. Beta-adrenergic blocking activity is 7x > than alpha-adrenergic blockers. Produces dose-

dependent in BP without

significant in HR or cardiac output

Esm

olo

l

0.25-0.5 mg/ kg IV push 1-2 mins followed by infusion of 0.05 mg/kg/min. If there is no response, repeat 0.5 mg/kg bolus

dose & infusion to 0.10 mg/kg/min. Maximum infusion rate=0.30 mg/kg/min

2-10 mins

10-30 mins

100 mg/ 10 ml vial; 2,500 mg in 250 mL D5W/NSS

48 hours

Hypotension, bradycardia, AV block, agitation, confusion, wheezing / bronchoconstriction, phlebitis

Short-acting beta-adrenergic blocking agent. At low doses, has little effect on beta2 receptors of bronchial & vascular smooth muscle

B. Blood pressure management in Acute Hypertensive ICH

Maintain MAP<130, but not lower than 110 mmHg

Sustained hypertension may alter cerebral autoregulation, promote progression of bleed and increase edema

Hypotension may result in cerebral hypoperfusion especially in the setting of increased intracranial pressure (ICP)

Absence of penumbra allows for more aggressive BP management

Bibliography

Adams H, Adams R, del Zoppo G, Goldstein L. Guidelines for the early management of patients with ischemic stroke. 2005 Guidelines update, a scientific statement from the Stroke Council of the American Heart Association. Stroke 2005;36:916-923.

Broderick JP, Adams HP, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council of the American Heart Association. Stroke 1999;30:905-915. Fogelholm R, Avikainen S and Murros K. Prognostic value and determinants of first day mean arterial pressure in spontaneous supratentorial intracerebral hemorrhage. Stroke 1997;28:1396-1400. Guyton A and Hall J. Guyton and Hall’s Textbook of Medical Physiology, 11

th ed. USA: WB Saunders; 2005.

Kidwell CS, Saver JL, Mattiello J, et al. Diffusion perfusion MR evaluation of perihematomal injury in hyperacute intracebral hemorrhage. Neurology 2001;57:1611-1617. Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation of cerebral blood flow surrounding acute (6-22hours) intracerebral hemorrhage. Neurology 2001;57:18-24. Qureshi A, Wilson D, Hanley D, Traystman R. No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage. Neurology 1999;52:266-272. Schellinger P, Fiebach J, Hoffman K, et al. Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra? Stroke 2003;34:1647-1680. The Brain Matters Stroke Initiative. Acute Stroke Management Workshop Syllabus. Basic Principles of Modern Management for Acute Stroke.

APPENDIX IV

Neuroimaging (CT and MRI) A. Hyperacute or Acute Ischemic Stroke

Plain CT scan of the head is the initial neuroimaging study of choice in acute stroke. The main objective is to exclude hemorrhagic stroke and stroke mimickers. A plain study obviates the need to wait for creatinine result.

CT scan is 100% sensitive in documenting intracranial hemorrhage (ICH) and 96% sensitive in documenting subarachnoid hemorrhage (SAH).

Cerebral infarcts are often not documented within 3 hours from stroke onset. However, 60% have “early” infarct signs when viewed very closely:

1. Dense MCA sign 2. Obscuration of the lentiform nucleus 3. Loss of the gray-white interphase along the lateral insula

(Insular ribbon sign) 4. Effacement of the sulci

In cases of neurologic deterioration, large infarcts or suspected hemorrhagic conversion, a follow-up plain CT of the head is recommended.

MRI has the technical advantage of documenting small lesions or those located in the brainstem or posterior fossa.

MRI can detect early infarction as early as 90 minutes using Diffusion Weighted Imaging (DWI).

Despite the superior diagnostic yield of MRI over CT, MRI is not recommended as routine evaluation of patients with acute ischemic stroke. It is more expensive, time-consuming and less readily available.

B. Intracerebral Hemorrhage

CT can accurately document the exact location of the hemorrhage and the presence of mass effect, ventricular extension and hydrocephalus.

In hypertensive ICH, a repeat plain CT scan after 24 hours of ictus is recommended especially in cases showing clinical deterioration to document hematoma enlargement and/or development of hydrocephalus.

Computation of Hematoma Volume (Kothari method)

Hematoma volume (in cc) = A x B x C

2 where: A= Largest diameter of hematoma (in cm)

B= Diameter perpendicular to A (in cm) C= Number of slices on CT scan with hemorrhage X slice thickness (in cm)

Count slice as 1 if size of hematoma is >75% of largest diameter

Count slice as 0.5 if size of hematoma is 25-75% of largest diameter

Disregard slice if size of hematoma is <25% of largest diameter

In suspected cases of AV malformation, aneurysm or tumor bleed, a contrast CT of the head may be warranted

C. Subarachnoid Hemorrhage

Plain CT of the head is strongly recommended as the initial procedure for diagnosis.

The diagnostic yield of CT goes down from 92% within the first 24 hours to 50% within 7 days of onset.

Bibliography

Brott T, Broderick J, Kothari R, et al. Early Hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1-5.

Culebras A, Kase C, Masdeu J, et al. Practice guidelines for the use of imaging in transient ischemic attacks and acute stroke. Stroke 1997;28:1480-1497. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304-1309. Osborne A. Diagnostic Neuroradiology, 1

st edition. USA: Mosby; 1994.

APPENDIX V

Early Specific Treatment For Ischemic Stroke A. Thrombolytic therapy

- Patients treated with IV recombinant tissue plasminogen activator (rtPA) within 3 hours of stroke onset are at least 30% more likely to have minimal or no disability at 3 months. - Streptokinase has no role in acute thrombolysis for ischemic stroke .

National Institute of Neurological Disorders and Stroke (NINDS) rTPA

guidelines

1. Dose of rtPA is 0.9 mg/kg (maximum 90 mg). Ten percent of total dose is given as IV bolus, the rest as infusion over 60 minutes.

2. rtPA is recommended within 3 hours of onset of ischemic stroke. The benefit of IV rtPA for acute ischemic stroke beyond 3 hours from onset of symptoms is not established. IV rtPA is not recommended when the time of onset of stroke cannot be ascertained reliably, including strokes recognized upon awakening.

3. Thrombolytic therapy is not recommended unless the diagnosis is established by a physician with expertise in diagnosing stroke and CT of the brain is assessed by physicians with expertise in reading this imaging study. If CT demonstrates early changes of a recent major infarction such as sulcal effacement, mass effect, edema or possible hemorrhage, thrombolytic therapy should be avoided.

4. Thrombolytic therapy cannot be recommended for patients with any of the following (NINDS Study):

a. Current use of oral anticoagulants or PT>15 seconds (INR>1.7) b. Use of heparin in the previous 48 hours or prolonged PTT>1.5x

normal c. Platelet count <100,000 mm3 d. Another stroke or a serious head injury within the previous 3

months e. Major surgery within the preceding 14 days f. Sustained pretreatment SBP>185 mmHg or DBP>110 mmHg

(when aggressive treatment necessary to lower BP) g. Rapidly improving neurological signs h. Mild, isolated neurological deficits, such as ataxia alone,

sensory loss alone, dysarthria alone, or minimal weakness i. Prior ICH j. Blood glucose <50 mg/dL or > 400 mg/dL k. Seizure at onset of stroke l. Gastrointestinal or urinary bleeding within preceding 21 days m. Recent myocardial infarction (within the previous 3 months)

5. Thrombolytic therapy should not be given unless emergent ancillary care and the facilities to handle bleeding complications are readily available.

6. Caution is advised before giving rtPA to persons with severe stroke (NIH Stroke Scale Score >22)

7. Because the use of thrombolytic drugs carries the real risk of major bleeding, whenever possible the risks and potential benefits of rtPA should be discussed with the patient and his or her family before treatment is initiated.

8. Patients given rtPA should not receive antiplatelets or anticoagulants within 24 hours of treatment.

B. Antithrombotic therapy

1. International Stroke Trial (IST)

- Multicenter randomized clinical trial of 19,435 patients - Regimen: Aspirin 300-325 mg/day vs. no aspirin

Heparin SC vs. no heparin 5,000 units bid or 12,500 units bid

- Started within 48 hours of stroke onset for 14 days or until discharge

- Results: Aspirin

- Fewer recurrent stroke within 14 days - Fewer deaths and dependency at 6 months

Heparin - No benefit even at 6 months - If used should not exceed 5,000 units bid

2. Chinese Acute Stroke Trial (CAST)

- 21,106 patients randomized - Aspirin 160 mg/day vs. placebo - Started within 48 hours of stroke onset - Results:

Risk of recurrent stroke or vascular death: Aspirin 5.3% Placebo 5.9% (p=0.03)

3. Meta-analysis on low molecular-weight heparin (LMWH) and

heparinoids in acute ischemic stroke involving 2,855 patients has shown that treatment was associated with significant reduction in venous thromboembolism (DVT and pulmonary embolism). LMWH has no significant effect on reducing death and disability at 6 months. Symptomatic ICH was not significantly increased.

C. Neuroprotection

1. Neuroprotective Interventions: The 5 “H” Principle

Avoid hypotension, hypoxemia, hyperglycemia or hypoglycemia and hyperthermia (fever) during acute stroke in an effort to "salvage" the ischemic penumbra

Avoid Hypotension

Aggressive BP lowering is detrimental in acute stroke. Manage hypertension as per recommendation (Appendix III)

Avoid Hypoxemia

Routine oxygenation in all stroke patients is not warranted

Maintain adequate tissue oxygenation (target O2 saturation >95%)

Do arterial blood gases (ABG) determination or monitor oxygenation via pulse oximeter

Give supplemental oxygen if there is evidence of hypoxemia or desaturation

Provide ventilatory support if upper airway is threatened or sensorium is impaired or ICP increased.

Avoid hypoglycemia or hyperglycemia

Hyperglycemia can increase the severity of ischemic injury (causes lactic acidosis, increases production of free radicals, worsens cerebral edema and weakens blood vessels), whereas hypoglycemia can mimic a stroke

Prompt determination of blood glucose should be done in all stroke patients

Ensure tight glycemic control at 80-110 mg/dL

Avoid glucose-containing (D5) IV fluids. Use isotonic saline (0.9% NaCl)

Avoid Hyperthermia

Fever in acute stroke is associated with poor outcome possibly related to increased metabolic demand, increased free radical production and enhanced neurotransmitter release.

For every 1 C increase in body temperature, the relative risk of death or disability increases by 2.2.

Search for the source of fever.

Treat fever with antipyretics and cooling blankets.

Maintain normothermia. D. Neuroprotectants

Neuroprotectants are drugs that:

o Protect against excitotoxins and prolong neuronal survival o Block the release of glutamate, free radicals, inflammatory cytokines,

and the accumulation of intracellular calcium cations.

Several neuroprotective drugs have reached phase III clinical trials, but most had negative or disappointing results except for citicoline. Data-pooling analysis on four trials involving 1,652 patients with ischemic stroke show that treatment with citicoline within the first 24 hours increases the probability of global recovery (NIHSS, mRS, BI) by 30% at 3 months.

CDP–choline helps increase phosphatidylcholine synthesis and inhibition of phospholipase A2 within the injured brain during ischemia

Several phase III clinical trials (e.g. SAINT II, FAST-MAG) are currently underway

Bibliography

Adams H, Adams R, del Zoppo G, Goldstein L. Guidelines for the early management of patients with ischemic stroke. 2005 Guidelines update, a scientific statement from the Stroke Council of the American Heart Association. Stroke 2005;36:916-923. Adams H, Brott T, Furlan A, et al. Guidelines for thrombolytic therapy for acute stroke: supplement to the guidelines for the management of patients in acute ischemic stroke. Circulation 1996;94:1167-1174. Adams H. Emergent use of anticoagulation for treatment of patients with ischemic stroke. Stroke 2002;33:856-861. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):483S-512S. Bath P, Iddenden R, Bath, F. Low Molecular weight heparins and heparinoids in acute ischemic stroke. a meta-analysis of randomized controlled trials. Stroke 2000;31:1770-1778. Chen Z, Sandercock P, Pan H, et al. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40,000 randomized patients from the CAST and IST. Stroke 2000;31:1240-1249. Chinese Acute Stroke Trial Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997;349:1641-1649. Clark WM, Warachi SJ, Pettigrew LC, et al; for the Citicoline Stroke Study Group. A randomized dose response trial of citicoline in acute ischemic stroke patients. Neurology 1997;29:671-678. Coull BM , Willliam LS, Goldstein LB. et al. Anticoagulants and antiplatelets in acute ischemic stroke. Report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association. Neurology 2002;59:13-22. Davalos A, Castillo J, Alvarez-Sabin J, et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke 2002;33:2850-2857. International Stroke Trial Collaborative Group. The International Stroke Trial: a randomised trial of aspirin, subcutaneous heparin, both or neither among 19,435 patients with acute ischemic stroke. Lancet 1997;349:1569-1581. Labiche LA, Grotta JC. Clinical trials for cytoprotection in stroke. NeuroRx 2004;1:46-70.

Lyden P, Wahlgren N. Mechanism of action of neuroprotectants in stroke. Journal of stroke and cerebrovascular diseases.2000; 9(6): 9 – 14. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587. Practice advisory: Thrombolytic therapy for acute ischemic stroke-summary statement. Report of the Quality standards Subcommittee of the American Academy of Neurology. Neurology 1996;47:835-839.

APPENDIX VI

Anticoagulation In Acute Cardioembolic Stroke A. Cardioembolic sources

High Risk Low or Uncertain Risk

AF (valvular or non-valvular) Mitral valve Prolapse

Rheumatic mitral stenosis Mitral annular calcification

Prosthetic heart valves Patent foramen ovale (PFO)

Recent MI Atrial septal aneurysm

LV/LA thrombus Calcific aortic stenosis

Atrial myxoma Mitral valve strands

Infective Endocarditis

Dilated cardiomyopathy

Marantic endocarditis

B. Indications and contraindications for anticoagulation in patients with cardioembolic stroke

Probably Indicated Contraindicated

Intracardiac thrombus Bleeding diathesis

Mechanical prosthetic valve Non-petechial intracranial hemorrhage

Recent MI Recent major surgery or trauma

CHF Infective endocarditis

Bridging measure for long term anticoagulation

C. When considering anticoagulation in acute cardioembolic stroke, the benefits of anticoagulation in reducing early stroke recurrence should be weighed against the risk of hemorrhagic transformation. The latter is higher in patients with large infarction, severe strokes or neurological deficits and uncontrolled hypertension. D. How to anticoagulate

1. Requirements for IV anticoagulation of patients with cardiogenic source of embolism:

a. Heparin sodium in D5W b. Infusion pump, if available c. Activated partial thromboplastin time (aPTT) or clotting time

2. Procedure:

a. Start intravenous infusion at 800 units heparin/hour ideally using infusion pump. IV heparin bolus is not recommended.

b. Perform aPTT as often as necessary, every 6 hours if need, to keep aPTT at 1.5-2.5x the control. Risk for major hemorrhage, including intracranial bleed, progressively increases as aPTT exceeds 80 seconds.

c. Infusion may be discontinued once oral anticoagulation with coumadin has reached therapeutic levels or once antiplatelet medication is started for secondary prevention.

To date, there has been no trial directly comparing efficacy of unfractionated heparin vs LMWH in patients with acute cardioembolic stroke. LMWH has the advantage of ease of administration and does not require aPTT monitoring. Bibliography

Adams H. Emergent use of anticoagulation for treatment of patients with ischemic stroke. Stroke 2002;33:856-861. Hart R, Palacio S, Pearce L. Atrial fibrillation, stroke and acute antithrombotic therapy. Stroke 2002;33:2722- 2727. Moonis, M, Fisher M. Considering the role of heparin and low-molecular weight heparin in acute ischemic stroke. Stroke 2002;33:1927-1933.

APPENDIX VI

Early Specific Treatment of Hypertensive Intracerebral Hemorrhage

A. Medical Treatment for all ICH: The goals are to prevent complications and careful manage BP.

a. Maintain MAP <130, but not lower than 110 mmHg b. Manage increased ICP accordingly (see Appendix IX) c. Start anticonvulsants only if with seizures

The incidence of seizures is higher in ICH, especially in lobar hematomas.

The role of prophylactic anticonvulsants in deep hemorrhages is unclear. It is justified to withhold anticonvulsants until clinically indicated.

d. Prevent and treat respiratory complications. Endotracheal intubation is performed in patients to provide airway protection and in those in coma or with respiratory failure.

e. Prevent and treat infections. f. Maintain adequate nutrition. g. Ensure proper fluid and electrolyte balance; maintain

normothermia and normoglycemia. h. Rehabilitate early once stable. i. Practice bedsore precautions. j. Deep-vein thrombosis and pulmonary embolism prophylaxis

should be instituted (use antiembolic stockings or intermittent pneumatic compression devices)

B. Surgical Treatment

Its role depends on the size, extent and location of the hematoma, and patient factors.

a. There is evidence of increase in hematoma size by 33% within 24 hours of stroke onset in 38% of cases.

b. Considerations for surgical intervention: Non-surgical candidates

Patients with small hemorrhages (<10 mL) or minimal neurological deficits

Patients with GCS<5 except those who have cerebellar hemorrhage and brainstem compression

Patients with hematoma volume > 85 mL

Candidates for immediate surgery

Patients with cerebellar hemorrhage >3 cm who are neurologically deteriorating or have brainstem compression and hydrocephalus from ventricular obstruction

Patients with bleed associated with a structural lesion such as an aneurysm, AV malformation or cavernous angioma if there is a chance for good outcome and the vascular lesion is surgically accessible

Clinically deteriorating young patients with moderate or large lobar hemorrhage.

Ventricular drainage for patients with intraventricular hemorrhage with moderate to severe hydrocephalus.

All other patients may benefit from surgery

Patients with basal ganglia or thalamic hemorrhage

Patients with GCS >4

Patients with supratentorial hematoma with volume >30 cc Bibliography

Academy of Filipino Neurosurgeons Guidelines on the Management of Hypertensive ICH

Broderick JP, Brott TG, Tomsick T, et al. Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg 1990;72:195-199.

Broderick JP, Adams HP, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council of the American Heart Association. Stroke 1999;30:905-915.

Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1-5. Fujii Y, Tanaka R, Takeuchi S, et al. Hematoma enlargement in spontaneous intracerebral hemorrhage. J Neurosurg 1994;80:51-57.

Juvela S, Heiskanen O, Poranen A, et al. The treatment of spontaneous intracerebral hemorrhage. A prospective randomized trial of surgical and conservative treatment. J Neurosurg 1989;70:755-758.

Kazui S, Naritomi H, Yamamoto H, et al. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke 1996;27:1783-1787. Kothari RU, Brott T, Broderick JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304-1309.

APPENDIX VIII

Antiplatelets for Secondary Stroke Prevention A. Aspirin

1. Antiplatelet Trialist’s Collaboration 65 trials involving 60,196 patients with symptomatic atherosclerosis

(e.g., unstable angina, MI, TIA, stroke) Aspirin 50-1,500 mg/day vs control 23% odds reduction on composite outcome of MI, stroke or vascular

death Highest RRR was seen in the low (75-150 mg) and medium dose (160-

325 mg) groups 2. Mini-meta-analysis on aspirin among patient with prior stroke or TIA 10 trials involving 6,171 patients with prior TIA or non-disabling stroke Aspirin reduced the odds for the cluster of stroke, MI or vascular death

by 16% No difference in RRR for low (<100 mg), medium (300-325 mg) and

high doses (>900 mg) of aspirin B. Ticlopidine 1. Canadian American Ticlopidine Study (CATS)

1,072 patients with recent thromboembolic stroke Ticlopidine 250 mg bid vs placebo 30.2% risk reduction on composite outcome of MI, stroke, vascular

death over placebo

2. Ticlopidine Aspirin Stroke Study (TASS) 3,069 patients with recent TIA/cerebral infarction Ticlopidine 250 mg bid vs aspirin 1,300 mg od 12% risk reduction vs aspirin for stroke or death at 3 years

C. Clopidogrel

1. Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events (CAPRIE) 19,185 patients with prior stroke, MI or PAD Clopidogrel 75 mg/day vs aspirin 325 mg/day 8.7% RRR vs aspirin for combined endpoint of stroke, MI and vascular

death

2. Clopidogrel and Aspirin combination (Management of Atherothrombosis with Clopidogrel in High-Risk Patients with TIA or Stroke [MATCH])

7,599 patients with prior stroke or TIA and additional risk factors Clopidogrel-aspirin 75 mg/75 mg vs clopidogrel 75 mg No significant difference in composite outcome of ischemic stroke, MI,

vascular death or rehospitalization secondary to ischemic events

3. Clopidogrel for High Atherothrobotic Risk and Ischemic Stabilization,

Management and Avoidance (CHARISMA) 15,603 patients with either clinically evident cardiovascular disease or

multiple risk factors Clopidogrel 75 mg with low-dose aspirin (75-162 mg) vs low-dose

aspirin only Overall, clopidogrel/aspirin combination was not significantly more

effective than aspirin alone in reducing rate of MI, stroke or vascular death

Suggestion of benefit with combination treatment in patients with symptomatic atherothrombosis

D. Cilostazol

Cilostazol Stroke Prevention Study (CSPS) 1,095 patients with cerebral infarction in the past 6 months Cilostazol 100 mg bid vs placebo 41.7% RRR for recurrent stroke

E. Dipyridamole and asprin combination

1. European Stroke Prevention Study (ESPS 2) 6,602 patients with recent TIA or stroke randomized to placebo, aspirin

25 mg bid, extended-release dipyridamole 200 mg bid, or aspirin 25 mg + ER-dipyridamole 200 mg bid

Aspirin better than placebo; dipyridamole better than placebo; combination treatment better than either agent alone.

37.8% risk reduction for stroke with combination therapy over placebo No increased risk of major bleeding with combination treatment

2. European/Australasian Stroke Prevention in Reversible Ischemia Trial

(ESPRIT Trial) 2,739 patients with recent TIA or minor stroke of arterial origin

randomized to aspirin 30-325 mg/day or aspirin 30-325 mg od + dipyridamole 200 mg bid

20% risk reduction for composite outcome of stroke, MI, vascular death with combination therapy

No increased risk of major bleeding with combination treatment

Bibliography

Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126 (3 suppl):483S-512S Algra A, van Gijn J. Aspirin at any dose above 30 mg offers only modest protection after cerebral ischemia. J Neurol Neurosurg Psychiatry 1996;60:197-199. Antithrombotic Trialist Collaboration, Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction and stroke in high-risk patients. BMJ 2002;324:71-86.

Bhatt D, Fox K, Hacke W, et al; for the CHARISMA Investigators. Clopidogrel and aspirin alone for the prevention of atherothrombotic events. N Eng J Med 2006;354:1-12. CAPRIE Steering Committee. A randomized, blinded trial of clopidogrel vs aspirin in patients at risk of ischemic events. Lancet 1996:348:1329-1339. Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study 2. Dipyridamole and Aspirin in the secondary prevention of stroke. J Neurol Sci 1996;143:1-13. Diener HC, Bogousslavsky J, Brass LM, et al; for the MATCH Investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or TIA in high risk patients (MATCH): a randomized, double- blind, placebo- controlled trial. Lancet 2004;364:331-337. Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in Thromboembolic Stroke. Lancet 1989;1:1215-1220. Gotoh F, Tohgi H, Hirai S, et al. Cilostazol Stroke Prevention Study: a placebo controlled trial double-blind trial for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis 2000;9:147-157. Halkes PH, van Gijn J, Kappelle LJ, et al; for the ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischemia of arterial origin. Lancet 2006;367:1665-1673. Hass WK, Easton JD, Adams HP, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Eng J Med 1989;321:501-507.

APPENDIX IX

Management of Increased Intracranial Pressure A. Signs and symptoms of increased ICP

1. Deteriorating level of sensorium 2. Cushing’s triad

i. Hypertension ii. Bradycardia iii. Irregular respiration

3. Anisocoria

B. Management options for increased ICP General 1. Control agitation and pain with short-acting medications, such as NSAIDS

and opioids. 2. Control fever. Avoid hyperthermia. 3. Control seizures if present. May treat with phenytoin with a loading dose of

18-20 mg/kg IV then maintained at 3-5 mg/kg. Status epilepticus should be managed accordingly.

4. Strict glucose control between 80-110 mg/dL 5. No dextrose-containing IVF. Hyperglycemia may extend ischemic zone

(penumbra) and further cause cerebral edema 6. Use stool softeners to prevent straining.

Specific 1. Elevate the head at 30 to 45 degrees to assist venous drainage. 2. Give osmotic diuretics: Mannitol 20% loading dose at 1 g/kg, maintenance

dose at 0.5-0.75 mg/kg) to decrease intravascular volume and free water. 3. Lost fluids must be replaced. Hypertonic saline is an option and has the

advantage of maintaining an effective serum gradient for a prolonged period with lower incidence of rebound intracranial hypertension. Aim for serum osmolarity=310 mOsm/L. (Serum osmolarity = 2 (Na) + Glucose/18 + BUN /2.8)

4. Hyperventilate only in impending herniation by adjusting tidal volume and pCO2 between 25 to 30. This maneuver is usually effective only for approximately 6 hours. Otherwise maintain normal pCO2 between 35 and 40.

5. Carefully intubate patients with GCS 8 or less, or those unable to protect the airway.

6. Do CSF drainage in patients with intraventricular hemorrhage (IVH) or hydrocephalus.

7. Use barbiturates if all other measures fail. Available locally is thiopental (loading dose=10 mg/kg, maintenance dose titrated at 1-12 mg/kg/hour continuous infusion to achieve burst suppression pattern in EEG)

8. Consider surgical evacuation for mass lesions. 9. Consider decompressive hemicraniectomy in cases of malignant middle

cerebral artery infarcts

C. Sedatives and Narcotics Available Locally Drugs Usual

Dose Onset of Action

Duration of Effect

Comments

Availability/Dilution

Midazolam 0.025-0.35 mg/kg

1 to 5 min 2 hours Unpredictable sedation 15 mg/3 mL amp; 5 mg/5 mL amp; 50 mg in 100 mL NSS/D5W

Diazepam 0.1-0.2 mg/kg

Immediate 20 to 30 minutes

Sedation can be reversed with flumazenil (0.2-1 mg at 0.2 mg/min at 20 min interval, max dose 3 mg in one hour)

10 mg/2 mL amp; 50 mg in 250 mL NSS/D5W

Propofol 5-50 ug/kg/min

<40 secs 10 to 15 min

Expensive (10 mg/mL) 100 mL vial (premixed)

Ketorolac 50-100 mg IV

1 hour 6 to 8 hours

NSAID 30 mg/mL amp

Tramadol 50-100 mg IV

1 hour 9 hours Centrally acting synthetic analgesic compound not chemically related to opiates but thought to bind to opioid receptors and inhibit reuptake of NE and serotonin

50 mg/ 2 mL amp; 100 mg/2 mL amp

Fentanyl 50-100 ug/hour

1-2 mins >60 min Can be easily reversed with naloxone (0.4-2 mg IVP; repeat at 2-3 min intervals, max dose 10 mg) * 110x more potent than morphine

100 ug/2 mL; 2,500 ug in 250 mL NSS/D5W

Morphine 2-5 mg/hour

5 mins >60 min Opioid 10 mg/mL gr 1/6; 16 mg/ mL gr 1/4

Bibliography

Ropper A, Daryl G, Diringer M et al. Neurological and Neurosurgical Intensive Care. 4th ed. USA: Lippincott

Williams & Wilkins; 2003. Wijdicks EFN. The Clinical Practice of Critical Care Neurology. 2nd ed. USA: Oxford University Press; 2003.

Special Section: Guidelines for the MANAGEMENT OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

MANAGEMENT OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

I. DIAGNOSIS OF SUBARACHNOID HEMORRHAGE (SAH) Clinical – may present with sudden, severe headache (thunderclap

headache), loss of consciousness or adult-onset seizures. Neurological examination – signs of meningeal irritation (i.e., neck rigidity),

altered or decreased level of consciousness, CN III or VI nerve palsy. Patients may or may not have focal neurological deficits

Emergent referral to a neurologist/neurosurgeon and transfer to a facility with capabilities of managing acute stroke are recommended.

II. NEURODIAGNOSTIC EXAMINATIONS

1. Non-contrast cranial CT scan should be done and interpreted immediately. Hyperdense blood in the basal cisterns is usually diagnostic, but parenchymal clot in the temporal or basal frontal, and intraventricular hemorrhage are also suggestive of an underlying aneurysm.

2. Lumbar tap with CSF analysis in the absence of focal neurological

signs is an option in the following cases:

Cranial CT scan is negative

Cranial CT scan is unavailable

Special circumstances (e.g., issues with CT scan cost) Multiple specimens (at least 3 tubes) should be collected to rule out

traumatic tap. Opening pressures should be measured.

3. Cerebral angiogram is the gold standard in determining the cause of SAH. Early angiography should be performed in all cases, whether poor- or good-grade SAH. If the initial angiogram is negative, a repeat angiogram should be performed after 2 weeks.

4. Good-quality CT angiogram and MR angiography are other options.

III. SAH GRADING

1. Hunt and Hess Classification is recommended for the clinical grading of SAH. Table 9: Hunt and Hess Classification

Grade Description

1 Asymptomatic, or mild headache, slight nuchal rigidity

2 Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy

3 Drowsiness, confusion, or mild focal signs

4 Stupor, moderate to severe hemiparesis, possibly early

decerebrate signs

5 Deep coma, decerebrate rigidity, moribund appearance

2. Fisher grading may be used as a guide in considering therapeutic options.

Table 10: Fisher Grading

Grade Description (Blood on CT)

1 No subarachnoid blood detected

2 Diffuse or vertical layers <1 mm thick*

3 Localized clot or vertical layer >1 mm thick*

4 Intracerebral or intraventricular clot with diffuse or no SAH

*“Vertical layer” refers to blood in the subarachnoid spaces including in the interhemispheric fissure and cisterns

IV. GENERAL SYMPTOMATIC TREATMENT 1. Absolute bed rest in a quiet, comfortable environment 2. Cardiac monitoring and frequent assessment of neuro-vital signs 3. Soft diet for alert patients, nasogastric-tube (NGT) feedings if with

impaired consciousness 4. Analgesics, including opiates for headache. Avoid aspirin and other

NSAIDs 5. Paracetamol and cooling blankets, if febrile 6. Maintenance of euglycemia 7. Sedatives, if agitated 8. Antiemetics, as needed for nausea and vomiting 9. Stool softeners

V. EARLY SPECIFIC TREATMENT

1. Nimodipine: A systematic review showed a significant reduction in poor outcomes with calcium antagonists for SAH. The evidence rests mainly on one large trial with oral nimodipine. It is uncertain whether nimodipine acts through neuroprotection or through reduction of the frequency of vasospasm, or both. Nimodipine 60 mg every 4 hours by mouth or NGT for 3 weeks is recommended.

2. Anticonvulsants: Short-term anticonvulsants are recommended for patients with documented seizures in the acute phase of SAH. Although no randomized trial has proven that prophylactic anticonvulsants in SAH is effective, they can be considered in patients with significant cortical damage, thick cisternal clot, parenchymal hemorrhage, or those in coma. Phenytoin is the recommended anticonvulsant, given as a 15 mg/kg IV loading dose followed by 3 to 5 mg/kg/day in divided doses.

3. Steroids: Corticosteroids have no proven role and are not recommended for use in SAH.

4. Antifibrinolytic agents are not recommended. Although they reduce the risk of rebleeding, they are associated with a higher rate of cerebral ischemia.

5. Manage increased ICP

6. BP management: Although the best antihypertensive agent and BP remains unsettled, IV nicardipine to a target SBP<150 in the pre-operative phase is reasonable.

VI. PREVENTION AND MANAGEMENT OF VASOSPASM 1. Monitoring: Serial transcranial Doppler (TCD) is recommended for the

diagnosis and monitoring of vasospasm. 2. Maintenance of euvolemia: Evidence on the use of blood volume

expansion alone or in combination with induced hypertension and hemodilution (triple H therapy) in the prophylaxis and management of secondary ischemia (vasospasm) following aneurysmal SAH is lacking.

3. Endovascular angioplasty (chemical +/- mechanical) is a effective way of managing vasospasm. Intervention has to be early before clinical signs suggesting irreversible infarction (i.e., hemiplegia) are present.

4. Treatment strategies undergoing current investigation include intravenous magnesium sulfate and statins.

VII. TREATMENT OF SAH

Excluding the aneurysm from the circulation is the main goal of treatment. Obliteration the aneurysm can be achieved through surgical clipping or endovascular coiling. VIII. TIMING OF SURGERY 1. Definitions:

Early surgery is surgery performed within 72 hours from ictus Late surgery is surgery performed more than 3 days from ictus.

2. Indications:

a. Early, immediate surgery is recommended for good- to moderate-grade (Hunt and Hess I-III) aneurysmal SAH patients to minimize the chance of a devastating rebleed.

b. For poor grade patients (Grade IV-V), early surgery is recommended in the presence of:

Hematoma

Hydrocephalus

Surgery may be delayed in the presence of:

Ischemia or infarction

Severe angiographic vasospasm

Casted ventricles

Diffuse SAH (Fisher Grade III) Complex aneurysm on angiography.

c. A maximum cut-off age for early surgical management (for the elderly) is not recommended in the absence of organ failure.

IX. COILING 1. Can be performed early in both good- and poor-grade patients. 2. Reduces the rebleed rate for poor-grade patients who would otherwise be

treated conservatively. 3. Vasospasm is not a contraindication and can be dealt with endovascularly

during coiling 4. Can be performed under local anesthesia if needed.

X. WHERE TO ADMIT SAH patients should be admitted at the Stroke Unit or Intensive Care Unit. In the absence of an ASU/ICU, patients may be placed in a quiet, regular room with very close monitoring.

XI. NURSING ISSUES: SOLICITUDE, THOUGHTFULNESS, PROTECTIVENESS 1. Acute Phase

a. Care must be exercised to prevent further ICP increase b. There should be close monitoring of fluid status and for possible

secondary cardiac, respiratory or metabolic insults. c. Persistent headache, deteriorating level of consciousness, other

signs of increased ICP and development of focal neurological deficits should be recognized for urgent referral to a neurologist or neurosurgeon.

2. Convalescent Phase

a. Presence of sensory or perceptual alterations, motor deficits, and impaired verbal communication and physical mobility should be addressed in nursing care.

b. Feelings of depression should be monitored. Emotional support and encouragement should be provided.

c. Upon discharge, patients and relatives should be educated on continuity of care, medication intake and follow-up

XII. REHABILITATION

1. Supportive rehabilitation is done initially in the pre-operative phase.

2. Early rehabilitation is recommended for all SAH patients in the post-operative period.

Bibliography

Academy of Filipino Neurosurgeons (AFN) Guidelines on the Management of Aneurysmal Subarachnoid Hemorrhage (unpublished). Alberico RA, Patel M, Casey S; et al. Evaluation of the circle of willis with three-dimensional CT angiography in patients with suspected intracranial aneurysms. Am J Neuroradiol 1995;16:1571-1578. Andaluz N, Tomsick TA, Tew JM, et al. Indications for Endovascular Therapy for Refractory vasospasm After Aneurysmal Subarahcnoid Hemorrhage. Surg Neurol 2002;58:131-138 Anderson GB, Steinke DE, Petruk KC et al. Computed tomographic angiography versus digital subtraction angiography for the diagnosis and early treatment of ruptured intracranial aneurysms. Neurosurg 1999;45:1315-1320. Anzalone N, Triulzi F, Scotti G. Acute subarachnoid hemorrhage: 3D time of flight MR angiography versus intra-arterial digital angiography. Neuroradiol 1995;37:257-261. Asano T, Takakura K, Sano K, et al. Effects of hydroxyl radical scavenger on delayed ischemic neurological deficits following aneursysmal subarachnoid hemorrhage: results of a multicenter, placebo-controlled double-blind trial. J Neurosurg 1996;84:792-803. Babikian V, Feldmann E, Wechsler L, et al. Transcranial doppler ultrasonography year 2000 update. J Neuroimaging 2000;10:101-115. Baker C, Prestigiacomo, et al. Short term perioperative anticonvulsant prophylaxis for the surgical treatment of low-risk patients with intracranial aneurysms. Neurosurg 1995;37:863-871. Butzkueven H, Evans AH, Pittman A, et al. Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology 2000;55:1315-1320. De Gans K, Nieuwkamp DJ, Rinkel G, Algra A. Timing of surgery in subarachnoid hemorrhage: a systematic review of literature. Neurosurg 2002;50:336-342. Feigin VL, Rinkel GJ, Algra A, et al. Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review. Neurology 1998;50:876-883. Findlay JM and Canadian Neurosurgical Society Practice Guidelines Review Group. Current management of aneurysmal subarachnoid hemorrhage Guidelines from the Canadian Neurological Society. Can J Neurol Sci 1997;24:161-170. Fisher CM, Kristler JP, Davis JM. Relation of Cerebral Vasospasm to Subarachnoid Hemorrhage visualized by CT Scanning. Neurosurg 1980;6:1-9. Greenberg, M. Handbook of Neurosurgery 2

nd ed. FL: Greenberg Graphics; 1991.

Haley EC Jr, Kassell NF, Apperson-Hansen C,. et al. A randomized, double-blind, vehicle controlled trial of Tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America. J Neurosurg 1997;86:467-474. Hope JK, Wilson JL, Thomson FJ. Three-dimensional CT angiography in the detection and characterization of intracranial berry aneurysm. Am J Neuroradiol 1996;17:437-445. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968;28:14-19.

ISAT Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with intracranial aneurysms: a randomised trial. Lancet 2002;360:1267-1274. Johansson M, Cesarini KG, Contant CF, et al. Changes in intervention and outcome in elderly patients with subarachnoid hemorrhage. Stroke 2001;32:2845-2949. Kassell NF, Haley EC Jr, Apperson-Hansen C, et al. Randomized, double-blind, vehicle controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg 1996;84:221-228. Lanzino G, Kassell NF. Double-blind, randomized, vehicle controlled study of high dose tirilizad mesylate in women with aneursymal subarachnoid hemorrhage. Part II. A cooperative study in North America. J Neurosurg 199a9; 90:1018-1024. Lanzino G, Kassell NF, Dorsch NW, et al. Double-blind, randomized, vehicle controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I. A cooperative study in Europe, Australia, New Zealand, and South Africa. J Neurosurg. 1999b;90:1011-1017. Lennihan, Laura MD, Mayer, Stephan MD, Fink, Matthew MD et al. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage: a randomized controlled trial. Stroke 2000; 31: 383-391. Linn FH, Rinkel GJ, Algra A, van Gijn J. Headache characteristics in subarachnoid hemorrhage and benign thunderclap headache. J Neurol Neurosurg Psychiatry 1998;65:791-793. Lysakowski C, Walder B, Costanza MC, Tramer MR. Transcranial Doppler versus angiography in patients with vasospasm due to a ruptured cerebral aneurysm: A systematic review. Stroke 2001;32:2292-2298. Mayberg, Marc MD, Batjer H. et al. Guidelines in the management of aneurysmal subarachnoid hemorrhage : A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke1994;25:2315-2328. Molyneux AJ, Kerr Rs, Yu LM, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups and aneurysm occlusion. Lancet 2005;366:809 -817. Ohman J, Heiskanen O. Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study. J Neurosurg 1989;70:55-60. Pickard JD, Murray GD, Illingworth R, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid hemorrhage: British aneurysm nimodipine trial. BMJ 1989;298:636-642. Pinto AN, Canhao P, Ferro JM. Seizures at the onset of subarachnoid hemorrhage. J Neurol 1996;243:161-164. Rhoney DH, Tipps LB, Murry KH, et al. Anticonvulsant prophylaxis and timing of seizures after aneurysmal subarachnoid hemorrhage. Neurology 2000;55:258-265. Rinkel GJE, Feigin VL, Algra A, et al. Calcium antagonists for aneurysmal subarachnoid hemorrhage (Review). The Cochrane Database of Systematic Reviews 2005. Issue 1. CD 00027.pub2 Rinkel GJE, Fiegin VL, Alga A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid hemorrhage. The Cochrane Database of Systematic Reviews 2004. Issue 4. CD 000483 pub2. Roos Y; for the STAR Study Group. Antifibrinolytic treatment in subarachnoid hemorrhage A randomized placebo-controlled trial. Neurology 2000;54:77-82. Sloan MA, Haley EC Jr, Kassell NF, et al. Sensitivity and specificity of transcranial doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage. Neurology 1989;39:1514-1518.

Sloan Mam Burch CM, Wozniak MA, et al. Transcranial doppler detection of vertebrobasilar vasospasm following subarachnoid hemorrhage. Stroke 1994;25: 2187-2197. Tolias CM, Choksey MS. Will increased awareness among physicians of the significance of sudden agonizing headache affect the outcome of subarachnoid hemorrhage? Coventry and Warkwickshire Study: audit of subarachnoid hemorrhage. Stroke 1996;27:807-812. Treggiari-Venzi M, Suter P, Romand JA. Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensive care. Neurosurg 2001;48:249-262. van Gijn J and Rinkel GJE. Subarachnoid hemorrhage: diagnosis, causes and management. Brain 2001;124:249-279. van Gijn J, van Dongen KJ. Computed tomography in the diagnosis of subarachnoid hemorrhage and ruptured aneurysm. Clin Neurol Neurosurg 1980a;82:11-24. van Gijn J, van Dongen KJ. The time course of aneurysmal hemorrhage on computed tomograms. Neuroradiol 1982;23:153-156. van der Wee N, Rinkel GJ, Hasan D, van Gijn J. Detection of subarachnoid hemorrhage on early CT: is lumbar puncture still needed after a negative scan? J Neurol Neurosurg Psychiatry 1995; 58:357-359. Velthuis BK, van Leeuwen MS, Witkamp TD, et al. CT angiography: source images and postprocessing techniques in the detection of cerebral aneursyms. AJR AM J Roentgenol 1997;169:1411-1417. Velthius BK, Rinkel GJ, Ramos LM, et al. Subarachnoid hemorrhage: aneurysm detection and preoperative evaluation with CT angiography. Radiology 1998;208:423-430. Velthius BK, Rinkel GJ, Ramos LM, et al. Computerized tomography angiography in patients with subarachnoid hemorrhage: from aneurysm detection to treatment without conventional angiogram. J Neurosurg 1999a;91:761-767. Vermeulen M. Lindsay KW, Murray GD, et al. Antifibrinolytic treatment in subarachnoid hemorrhage. N Engl J Med 1984. 311: 432-7. Vermeulen M, van Gijn J. The diagnosis of subarachnoid hemorrhage. J Neurol Neurosurg Psychiatry 1990;53:365-372. Vermeulen M, Lindsay KW, Murray GD, et al. Antifibrinolytic treatment in subarachnoid hemorrhage. N Engl J Med 1984;311:432-437. Wardlaw JM, White PM. The detection and management of unruptured intracranial aneurysm (Review). Brain 2000;123:205-221. Whitfield PC, Kirkpatrick PJ. Timing of surgery for aneurysmal subarachnoid hemorrhage. Cockrane Database System Rev 2001 (2): CD 001697 Wiebers D, Fiegen V, Brown R. Handbook of Stroke, PA: Lippincott-Raven Publishers; 1997. Yvo R, Rinkel G, Vermeulen M, et al. Antifibrinolytic therapy for aneursymal subarachnoid hemorrhage: a major update of a cochrane review. Stroke 2003;34:2308-2309.

Guidelines for STROKE REHABILITATION

STROKE REHABILITATION I. ACUTE POST-STROKE REHABILITATION

A. Initial Brief Assessment

Assessment for complications and prior and current impairment: 1. Risk factors for recurrent stroke and coronary heart disease 2. Medical comorbidities (DM, hypertension, increase ICP, re-bleed,

re-stroke) 3. Consciousness and cognitive status 4. Brief swallowing assessment 5. Skin assessment and pressure ulcers 6. Mobility and need for assistance of movement

Patient with stroke during acute phase

Obtain medical history and physical examination. Initial assessment of complications, impairment and rehabilitation needs

including NIHHS, GCS, MRS, FIMS/Barthel Index.

Initiate secondary prevention and prevention of complications.

Acute post-stroke patient assessed for rehabilitation services.

MILD STROKE

Obtain medical history and physical examination. Determine nature and extent of rehabilitation needs and services based on

stroke severity, functional status and social support.

MODERATE STROKE

SEVERE STROKE

Go to II, III or IV. Go to II. Go to II.

7. Deep-vein thrombosis (DVT) risk assessment B. Assessment of Rehabilitation Needs

1. Prevention of complications: swallowing problems, skin breakdown, DVT, bowel and bladder dysfunction, malnutrition, pain, contractures, SHS/CRP, pulmonary.

2. Assessment of impairments: communication impairments, motor impairment, cognitive deficits, visual and spatial deficiency, psychological or emotional deficits, sensory deficits.

3. Psychosocial assessment and family or caregivers support 4. Assessment of function (e.g., functional independence measure or

FIM). 5. Financial support.

II. INPATIENT REHABILITATION

Post-stroke patient in inpatient rehabilitation

Determine level of care based on medical status, cognitive and motor function, social support, and access to care and services.

Discuss rehabilitation program with patient and family. Determine and document treatment plan

Reassess progress, future needs and risks with team.

Is patient progressing toward treatment goals?

NO

Address treatment adherence and barriers to improvement. If medically unstable, refer to

acute services. If with other health factors, refer to other health services.

Severe stroke and/or maximum dependence, or poor prognosis for functional recovery?

Educate patient, family, caregiver about future plans

and home therapy. Discharge patient to the home

or community. Go to IV.

Is patient ready for community living?

Continue inpatient rehabilitation.

Go to III.

Initiate rehabilitation programs and interventions.

YES

NO YES

YES NO

A. Reassessment of Rehabilitation Progress 1. General (medical status) 2. Functional status (FIM, etc.): Mobility, activities of daily living (ADL)

and instrumental ADLs, communication, nutrition, cognition, mood/affect/motivation, sexual function

3. Family support: Resources, caretaker, transportation 4. Patient and family adjustment 5. Reassessment of goals 6. Risk for recurrent cerebrovascular events

III. OUTPATIENT REHABILITATION

Post-stroke patient ready for home

Does patient need outpatient rehabilitation services?

Reassess progress, rehabilitation interventions and optimal environment for outpatient rehabilitation.

Discuss shared decision regarding rehabilitation program and treatment plan with patient and family. Continue secondary prevention.

Continue rehabilitation intervention at nearby center or hospital, or use home rehabilitation services.

Did patient plateau or achieve optimal function?

Reassess periodically. Go to IV.

Go to IV.

YES

NO

NO

YES

A. Assessment of Discharge Environment 1. Functional needs 2. Motivation and preferences 3. Intensity of tolerable treatment: Equipment, duration 4. Availability and eligibility 5. Transportation 6. Home assessment for safety

IV. COMMUNITY–BASED REHABILITATION

Post-stroke patient ready for community living

Does patient need community-based rehabilitation services?

Determine optimal environment for community-based rehabilitation.

Discuss shared decision regarding rehabilitation program and treatment plan with patient and family.

Continue rehabilitation intervention with patient and family/caregiver education.

Did patient plateau or achieve optimal function?

Reassess periodically. Discharge to the home or community setting.

Arrange primary-care follow-up.

Provide home rehabilitation program.

Arrange primary-care follow-up. Provide home rehabilitation

program. YES

NO

NO

YES

A. Assessment of Discharge Environment 1. Functional needs 2. Motivation and preferences 3. Intensity of tolerable treatment: Equipment, duration 4. Availability and eligibility 5. Transportation 6. Home assessment for safety 7. Maximal patient functioning

Guidelines for the NURSING MANAGEMENT of STROKE PATIENTS

NURSING MANAGEMENT OF STROKE PATIENTS I. PREVENTIVE CARE

General Objective

Specific Objectives

Process Outcome

1. Nurses will provide preventive care through health education activities based on identified learning needs.

Provide information on stroke, risk factors, lifestyle modification and regular medical check-ups.

1. A nurse will implement a health education program (HEP) approved or published by a duly accredited or recognized health agency. 2. A nurse will implement the HEP appropriate for the people’s level of understanding.

3. A nurse will use appropriate, available teaching material.

4. A nurse will actively participate in fora on health education on stroke prevention.

1. People understand risk factors and show interest in modifying lifestyle. 2. Incidence of stroke decreases. 3. Awareness increased. 4. Use of published materials increase participation in stroke prevention fora.

2. Nurses will actively identify patients with risk factors.

Identify people who are at risk for developing stroke.

1. The nurse will implement assessment based on established guidelines on stroke risk factors and will use a risk-assessment nursing framework. 2. The nurse will appropriately refer identified people high risk for stroke. 3. The nurse will report and document identified people high risk for stroke.

1. Early detection, referral and management of identified at-risk people. 2. Risk identification implemented in a standardized manner. 3. Contribute factual, accurate data due to existing

stroke data banks.

3. Nurses will be actively involved in HEP regarding lifestyle modification.

Identify, promote and participate in available programs regarding lifestyle modification.

1. The nurse will identify agencies in the community that have programs for lifestyle modification for stroke prevention. 2. The nurse will recommend available programs for lifestyle modifications. 3. The nurse will facilitate referral to appropriate community or health care agency regarding lifestyle modification.

1. Increased awareness of available facilities and programs regarding lifestyle modification. 2. Increased adherence to lifestyle modification.

II. CURATIVE CARE

General Objective

Specific Objectives

Process Outcome

1. Nurses will promptly identify patient’s needs by performing proper health assessment with emphasis on neurological assessment techniques.

1. Promptly identify and prioritize patient’s needs. 2. Use and perform proper neurological assessment techniques.

1. Nurses will assess patients comprehensively using current and acceptable neurological assessment tools. 2. Nurses will correlate patient’s history with signs and symptoms. 3. Nurses will identify priority patient needs based on assessment. 4. Nurses will prioritize and facilitate series of diagnostic examinations according to stroke guidelines and will have nursing responsibilities

1.Early needs identification and prioritization. 2. Immediate initiation of management.

3. Early transfer and admission to hospital with stroke or intensive care unit.

before, during and after the procedure, including patient safety and informed consent.

2. Nurses will provide quality nursing care based on the identified patient needs in collaboration with other member of the health team, utilizing a holistic approach.

Plan and manage nursing care based on patient’s condition, needs and priorities: a. Physiologic care b. Safe Measures c. Comfort Measures d. Therapeutic environment e. Prevention of complications and infections f. Spiritual and psychosocial care

1. Nurses will implement emergency nursing measures if needed. 2. Nurses will closely monitor, document and report neuro-vital signs. 3. Nurses will provide safety measures, such as a. Aspiration precautions b. Fall precautions c. Use of restraints d. Seizure precautions 4. Nurses will provide comfort measures, such as: a. Linen changes b. Personal hygiene c. Turning d. Proper positioning e. Range of motion (ROM) 5. Nurses will provide a therapeutic environment a. Proper ventilation and lighting b. Minimize noise c. Proper orientation to time, place and person d. Provisions of window murals in every room 6. Nurses will prevent complications and possible infections by: a. Establishing patent airway b. Monitoring and maintaining BP c. Observing and

1. Early identification and assessment of disease progression 2. No incidence of falls and aspirations. 3. No bedsores, contractures and muscular atrophy. 4. Healing environment attained. 5. Complications and infections prevented 6. Psycho-emotional and spiritual upliftment 7. No medication errors; medications adhere to. 8. Self expression using alternative means, if

providing catheter and tube care d. Monitoring input and output e. Monitoring and prevention of increased ICP f. Nutrition and hydration 7. Nurses will provide spiritual and psychosocial care: a. Alleviation of anxiety by encouraging verbalization of feelings b. Guidance in identifying positive coping mechanisms c. Respect of patient’s beliefs and culture d. Facilitation of patient’s spiritual needs 8. Nurses will apply the principles of Bioethics in the Practice of Nursing Care. 9. Nurses will administer medications observing the 10 R’s. 10. Nurses will establish alternative means of communication if necessary. 11. Nurses will assess patient’s capabilities in performing ADLs and assist in identifying alternative means.

needed. 9. Patient’s independent functions maximized; disabilities correctly addressed. 10. Cooperation and active participation of clients and significant others. 11. Complete, accurate records 12. Early medical intervention 13. Utilization of other health and community resources.

III. REHABILITATIVE AND PROMOTIVE CARE

General Objective

Specific Objectives

Process Outcome

1. Nurses will focus on early rehabilitation and discharge planning.

1. Assist the patient towards maximum functional capacity. 2. Discuss the care plan with the patient and significant others. 3. Involve the patient’s family and significant others in decision making and the care plan.

1. Nurses will initiate rehabilitation upon admission. 2. Nurses will assist the patient in performing ADLs in collaboration with other health team members. 3. Nurses will educate patient on alternative, physiologically safe sexual practice (as indicated). 4. Nurse will include significant others in providing specific nursing care, such as provisions of hygiene, nutrition, turning, positioning, pulmonary toile, ROM exercises, and other care. 5. Nurses will ensure good compliance to medications and provide options for compliance to outpatient follow-up 6. The nurse will collaborate with the family and significant others in the care plan.

1. Performance of simple ROM exercises and ADLs by patient with minimal or no supervision. 2. Maintenance of sexual function. 3. Performance of simple nursing procedures by significant others with minimal or no supervision from nurses. 4. Compliance to treatment regimen and adherence to outpatient follow-up 5. Active participation of patient and family in care plan.

2. Nurses will assist in sustaining and maintaining patient’s healthy, productive lifestyle.

1. Provide guidelines for home care. 2. Guide patient in lifestyle modification based on identified risk

1. Nurses will provide a discharge care plan containing the following: a. Activity and exercise b. Medication regimen c. Symptoms needing referral d. Prescribed diet e. Medical follow-up

1. Adherence of patient and family to prescribed discharge care plan. 2. Compliance to alternative

factors. 3. Assist patient in accepting and adapting to disability.

schedule f. Special care to be provided 2. Nurses will facilitate referrals to community resources. 3. Nurses will identify appropriate lifestyle modification suited to the patient’s current status. 4. Nurses will involve patient in diversion activities that will enhance self-esteem. 5. Nurses will involve family member in the care plan.

lifestyle. 3. Motivation and stimulation of patient’s interest in self-enhancing activities. 4. Maximal patient potential. 5. Active participation of family members.

Guidelines for the ESTABLISHMENT and OPERATION of STROKE UNITS

ESTABLISHMENT and OPERATION of STROKE UNITS

I. THE STROKE CENTER A. Major Aspects of Acute Stroke Care in Stroke Center

1. Acute Stroke Teams: Hospital-based stroke teams should be available round-the-clock, seven days a week in order to evaluate within 15 minutes any patient who may have suffered a stroke.

2. Written Care Protocols: The availability of written protocols is key in reducing time to treatment and treatment complications.

3. Emergency Medical Services: Emergency medical services (EMS) are vital in the rapid transport and survival of stroke patients.

4. Emergency Department: The emergency department staff should be trained in diagnosing and treating stroke and have good lines of communication with both EMS and the acute stroke team.

5. Stroke Unit: Where patients can receive specialized monitoring and care.

6. Neurosurgical Services: These should be provided to stroke patients within two hours of when the services are deemed necessary.

7. Support of the Medical Organization: The facility and its staff, including administration, should be committed to the Stroke Unit

8. Neuroimaging: There must be capability to perform an imaging study within 25 minutes of the physician¹s order. A physician should evaluate the image within 20 minutes of completion.

9. Laboratory Services: Standard laboratory services should be available round-the-clock, seven days per week at a Primary Stroke Center.

10. Outcomes/Quality Improvement: Primary Stroke Centers should have a database or registry for tracking the type and number of stroke patients seen, their treatments, timelines for treatments, and some measurements of patient outcome.

11. Educational Programs: The professional staff should receive at least eight hours per year of continuing medical education credits. In addition to professional education, the Stroke Center should plan and implement at least two annual programs to educate the public about stroke prevention, diagnosis and availability for emergency treatment.

B. Definition of a Stroke Unit A Stroke Unit is a hospital unit that cares for stroke patients exclusively or almost exclusively, with specially trained staff and a multidisciplinary approach to treatment and care.1

C. Characteristics of a Stroke Unit Organization

Coordinated multidisciplinary team care

Nursing integration with multidisciplinary care

Involvement of caregivers in rehabilitation process Specialization

Medical and nursing interest

Expertise in stroke and rehabilitation Education

Education and training program for staff, patients and caregivers D. Goals of a Stroke Unit 1. Improve chances of survival 2. Reduce disability 3. Shorten length of hospital stay 4. Shorten length of rehabilitation E. Types of Stroke Units

E1. Acute Admission Units: 1. Intensive Care Units – dedicated stroke unit with facilities such as ventilators and intensive invasive and non-invasive monitoring equipment. The units focus on the very acute care for a selected group of acute stroke patients and have little or no focus on rehabilitation.

2. Acute stroke unit – dedicated stroke units that accept patients acutely but discharge them early (within 7 days) and have no or at best a modest focus on rehabilitation. The units usually do not have intensive care facilities, but usually have facilities for non-invasive monitoring of vital signs.

3. Combined acute/rehabilitation stroke unit – dedicated stroke units which accept stroke patients acutely for acute treatment combined with early mobilization and rehabilitation for an average period of at least one to two weeks. 4. Mixed acute units – units that treat stroke patients and patients with other diagnoses. The units accept patients acutely. Some have a program of care similar to acute stroke units while others have a program similar to a combined unit.

E2. Delayed admission unit 1. Rehabilitation stroke unit – dedicated units that accept patients after a minimum delay of seven days after stroke onset. The units focus on rehabilitation. 2. Mixed assessment/rehabilitation unit – wards or units which have an interest and expertise in the assessment and rehabilitation of disabling illness, but do not exclusively manage stroke patients.

E. Effects of Stroke Unit Care on Recovery

Analysis on Cochrane Data Base involving 23 trials showed significant reduction of death (OR; 0.88), death or dependency (OR; 0.75) and death or institutionalization (OR; 0.77) when patients were treated in a stroke unit compared with those treated in general wards.2

Two trials evaluated the long-term effects of stroke unit care. On the 5-year follow-up, admission in combined acute/rehabilitation stroke units reduced death (OR; 0.59, NNT=9), death or dependency (OR; 0.36, NNT=6) and death or institutionalization (OR; 0.48, NNT=9). Ten-year follow-up of patients admitted in combined acute/rehabilitation stroke units similarly showed a reduction in death (OR; 0.45), death or dependency (OR; 0.45) and death or institutionalization (OR;0.42).3-5 Patients admitted in a rehabilitation stroke unit even after a minimum delay of seven days post-stroke resulted in reduced death (OR; 0.66, NNT=10) and death or dependency (OR; 0.83, NNT=90).6

The stroke unit benefits stroke patients of both sexes, all ages, and those with mild, moderate or severe strokes.2, 7 Comparing the different stroke unit models, the unit with the strongest evidence of benefit is the combined acute/rehabilitation stroke-unit model, and to some extent the dedicated rehabilitation stroke unit. 2

II. STROKE UNIT ORGANIZATION A. The Stroke Unit: Basic Equipment: 1. 4 to 8 beds 2. Cranial computerized tomography (available 24 hours) 3. Angiography (available 24 hours) 4. Ultrasound (continuous-wave, TC Duplex, transthoracic echocardiogram; transesophageal echocardiogram) 5. Monitoring (RR, Respiration, Holter, O2 saturation) 6. Emergency laboratory Monitoring: 1. Basic – Holter, blood pressure, O2 saturation, respiration, temperature 2. Special – Transcranial Doppler, embolus detection, electroencephalography,

central breathing patterns (sleep apnea) B. Tasks 1. Admission within the unstable phase (in general, <24 hours) 2. Monitoring of vital and neurological parameters 3. Immediate diagnosis (etiology, pathogenesis) 4. Immediate treatment and secondary prevention 5. In general, length of stay not longer than seven days

C. Patient Selection 1. Indications for Admission to the Stroke Unit

a. Acute stroke (< 24 hours) b. Awake, somnolent patient c. Symptoms fluctuating or progressive d. TIAs with high stroke risk (non-valvular AF, stenosis) e. Vital parameters unstable f. Thrombolysis, Anticoagulation g. New investigational treatment or procedure

2. Admission to Acute Stroke Unit Not Indicated a. Patients with severe consciousness impairment (should be

admitted to intensive care unit instead) b. Severely disabled patients by previous strokes c. Very old patients or those with multiple comorbidities

3. Patients with the following should be admitted to the intensive care unit instead of the acute stroke unit:

a. Stupor and coma b. Central respiratory disorders requiring artificial ventilation c. Space-occupying cerebral infarctions with risk of herniation d. Severe cardiopulmonary insufficiency e. Hypertensive-hypervolemic treatment

D. The Stroke Team 1. Personnel

a. Medical doctors b. Nurses c. Physiatrists d. Occupational therapists e. Speech pathologist f. Nutritionists g. Social workers

2. Personnel with special interest in stroke are medical doctors or other paramedical people who:

a. Have undergone continuing education on stroke and other related activities or subspecialties on stroke

b. Have been attending at least one national or international meeting on stroke in a year

c. Have undergone stroke fellowship or preceptorship training on stroke

d. Is a member or officer of a national or international organization devoted to stroke

III. HOSPITALS IN THE PHILIPPINES WITH ACUTE STROKE UNITS Table 11.

Hospitals Stroke Unit Type Contact Number

Metro Manila

East Avenue Medical Center Mixed acute units 9280611 loc.503

Jose Reyes Memorial Medical Center

ASU 7119491 loc 262

Makati Medical Center ASU

Manila Adventist Medical Center Mixed acute units 5259191 loc 324

Manila Doctors Hospital ASU 5243011

Manila Central University Mixed acute units 3672031 loc 1127

Philippine General Hospital ASU 5218450 loc 2406

Philippine Heart Center Mixed acute units 9252401 loc 2483

San Juan de Dios Medical Center Mixed acute units 8319731 loc 1226

St. Luke’s Medical Center ASU 7230101 loc 7399

Sto. Tomas University Hospital ASU 7313001 loc 2368

The Medical City Mixed acute units 6356789 loc 6281

Luzon

Mt. Carmel Diocesan General Hospital, Lucena

Mixed acute units 042-7102576

Lorma Medical Center, San Fernando, La Union

Mixed acute units 072-700-0000

Lucena United Doctors Hospital ASU 042-3736161

Cebu

Cebu Doctors Hospital ASU 032-2555555

Chong Hua Hospital Mixed acute units 032-2541461

ASU, acute stroke unit. IV. RECOMMENDATIONS Stroke patients should be treated in stroke units (Level I). Admission to stroke unit decreases death, dependency and institutionalization.

Stroke units should provide coordinated multidisciplinary care provided by medical, nursing and therapy staff who specialize in stroke care (Level I). Bibliography

1. Aboderin I, Venables G; for The Pan European Consensus Meeting on Stroke Management (WHO). J Int Med 1996;240:173-180.

2. Stroke Unit Trialists’ Collaboration. A systematic review of organized inpatient (stroke unit) care for stroke. Cochrane Library; Issue 4: 2002.

3. Indredavik B, Slordahl SA, Bakke F, et al. Stroke unit treatment long term effects. Stroke 1997;28:1861-1866.

4. Indredavik B, Slordahl SA, Bakke F, et al. Stroke unit treatment improves long term quality of life: a randomized controlled trial. Stroke 1998;29:895-899.

5. Indredavik B, Slordahl SA, Bakke F, et al. Stroke unit treatment: 10 year follow-up. Stroke 1990;30:1524-1527.

6. Lincoln NB, Husbands S, Trescoli C, et al. Five year follow-up of a randomized controlled trial of a stroke rehabilitation unit. BMJ 2000:320; 549.

7. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. Stroke Unit Trialists' Collaboration. BMJ 1997;314:1151-1159.

STRATEGY FOR IMPLEMENTATION OF GUIDELINES To effectively implement the guidelines set forth in the previous sections, it

is recommended that Stroke Centers be established in every region. Stroke Centers shall be designated according to levels as follows:

STROKE CENTER LEVEL

REQUIREMENTS

ACTIVITIES

I

Basic:

Physician/Municipal Health Officer

Optional:

Nurse/Midwife Barangay Health

Worker

Facilities: Municipal Health

Clinic

Stroke prevention and public

education Recognition of stroke Acute treatment of TIA and mild

stroke Referral of moderate and severe

strokes to Levels II or III centers Referral to Levels II or III centers for

diagnostic tests Rehabilitation Secondary prevention of stroke and

follow-up visits

II

Basic:

Neurologist (If not available, other physicians with special training in stroke)

Neurosurgeon Stroke nurse Radiologist Physiatrist

Facilities*: CT scan Electrocardiogram Laboratory Stroke Team/Unit Operating Room

Stroke prevention and public

education Recognition of stroke Acute treatment of TIA, mild,

moderate, and severe strokes Referral of complicated strokes to

Level III centers Referral to Level III centers for

further diagnostic tests Rehabilitation Secondary prevention of stroke and

follow-up visits

III

Basic:

Neurologist Neurosurgeon Stroke nurse Neuroradiologist Vascular surgeon Cardiologist Neurosonologist Physiatrist

Facilities: CT scan, MRI Cardiac diagnostic

services (including ECG, Doppler, echocardiogram)

Laboratory Angiography Stroke Unit Rehabilitation Unit Operating Room

Stroke prevention and public

education Recognition of stroke Acute treatment of TIA, mild,

moderate, and severe strokes Rehabilitation Secondary prevention of stroke and

follow-up visits Training of stroke personnel Research in stroke

LEVELS OF STROKE CARE

STROKE CENTER LEVEL

STROKE SEVERITY

I

II

III

TIA or Mild Stroke

√ √ √

Moderate Stroke

√ √

Severe Stroke

√ √

WORKING COMMITTEES Primary and Secondary Prevention of Stroke Dr. Artemio Roxas, Jr Dr. Raquel Alvarez Dr. Dante Morales Dr. Epifania Collantes Dr. Alejandro Diaz Dr. Vince De Guzman Dr. Romulo Esagunde Dr. Maria Cristina San Jose Dr. Fatima Collado Dr. Cymbeline Perez-Santiago Acute Stroke Management Dr. Abdias Aquino Dr. Maria Cristina San Jose Dr. Carlos Chua Dr. Lina Salud Dr. Ester Bitanga Dr. Vincent De Guzman Dr. Rhoderick Casis Dr. Gerardo Legaspi Spontaneous Intracerebral Hemorrhage Dr. Manuel Mariano Dr. Maria Cristina San Jose Dr. Rhoderick Casis Aneurysmal Subarachnoid Hemorrhage Dr. Manuel Mariano Dr. Rhoderick Casis Dr. Maria Cristina San Jose Dr. Gerardo Legaspi Dr. Peter Rivera Establishment and Operation of Stroke Units Dr. Jose Navarro Dr. Epifania Collantes Dr. Alejandro Baroque II Stroke Rehabilitation Dr. Betty Mancao Dr. Alvin Mojica Dr. Sharon Ignacio Dr. Josephine Bundoc Dr. Teresita Evangelista Dr. Cory Hidalgo Dr. Faith Legaspi Nursing Management of Patients with Stroke Ma. Isabelita Rogado, RN Noli Pagdanganan. RN Ferdinand Aganon, RN Veronica Honculada,RN Ana Merly Migo, RN Marilou Reyes, RN Lydia Bienes, RN Josefine Rivera, RN

Dr. Artemio Roxas, Jr.

2006 Edition Overall Chairperson

CORPORATE MEMBERS

Boehringer Ingelheim

LR Imperial Otsuka Philippines

Patriot Pharma Pfizer

Sanofi-Aventis Servier Philippines

UCB Philippines Therapharma

SSP Annual Conventions 1st Philippine Congress on Brain on Brain Attack Theme: Thinking Globally, Acting Locally October 1-2, 1999 Manila Midtown Hotel 2nd Philippine Congress on Brain Attack Theme: Organizing Stroke Services Year 2001 3rd Philippine Congress on Brain Attack Theme: Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH) August 2002 4th SSP Biennial Convention Theme: Ugaliing Tingnan, Ating Kalusugan, Upang Brain Attack ay Maiwasan August 20-22, 2003 Bethel Guest House, Dumaguete City 5th SSP Annual Convention Theme: Emerging Diagnostic Modalities & Therapeutic Interventions in Acute Brain Attack August 19-21, 2004 Taal Vista Hotel, Tagaytay City 6th SSP Annual Convention Theme: SSP Goes to the Community August 18-20, 2005 Fort Ilocandia Hotel, Laoag City 7th SSP Annual Convention Theme: SSP goes to Mindanao: Empowering the Community for Optimal Stroke Care August 21-23, 2006 The Marco Polo Hotel, Davao City

Stroke Society of the Philippines

BOARD OF TRUSTEES OFFICERS

President: Abdias V. Aquino, MD 1st Vice-President: Ester S. Bitanga, MD 2nd Vice-President: Jose C. Navarro, MD Secretary: Artemio A. Roxas Jr., MD Treasurer: Betty D. Mancao, MD P.R.O.: Carlos L. Chua, MD Immediate Past President: Joven R. Cuanang, MD

MEMBERS

Alejandro C. Baroque, MD Fatima R. Collado, MD

Ma. Epifania V. Collantes, MD Danilo J. Lagamayo, MD Manuel M. Mariano, MD Dante D. Morales, MD Peter P. Rivera, MD

Isabelita C. Rogado, RN Ma. Cristina San Jose, MD