BY

Dr. Khaled HelmyAl Mahmora Chest Hospital

BY

Dr. Khaled HelmyAl Mahmora Chest Hospital

Treatment Of HypertensionIn Diabetes

Treatment Of HypertensionIn Diabetes

Hypertension

&

Diabetes

Hypertension

&

Diabetes

Hypertension affecting  20–60% of patients with diabetes.

In type 2 diabetes, hypertension is often present as part of the metabolic syndrome while in type 1 diabetes, hypertension may reflect the onset of diabetic nephropathy.

Hypertension substantially increases the risk of both macrovascular and microvascular complications.

Hypertensive diabetic patients are also at increased

risk for diabetes-specific complications including

retinopathy and nephropathy.

In recent years, adequate data from well-designed

randomized clinical trials have demonstrated the effectiveness of aggressive treatment of hypertension in reducing both types of diabetes complications.

Hypertension Diabetes Hypertension Diabetes

Diabetes increases the risk of coronary events twofold in men and fourfold in women after menopause.

People with both diabetes and hypertension have approximately twice the risk of cardiovascular disease as non-diabetic people with hypertension

In the U.K. Prospective Diabetes Study (UKPDS) epidemiological study, each 10-mmHg decrease in mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes, 15% for deaths related to diabetes, 11% for myocardial infarction, and 13% for microvascular complications.

Hypertension Diabetes Hypertension Diabetes

Normotensive HypertensionNormotensive Hypertension

In recent years, adequate data from well-designed

randomized clinical trials have demonstrated that structural changes in vessels start 5 years before BP elevated .

patients who still have normal BP but have the high risk to develop high Bp(Patient at risk) are classified as normotensive hypertension and of course one of them is diabetic patients and they should be managed as soon as possible .

Strategy for management of Hypertensive Diabetic pts

Strategy for management of Hypertensive Diabetic pts

Proper blood sugar control .

Achieve target level of BP control for

diabetic patients

Early Detection of both diabetes and

hypertension complications & manage them

as well as delay their progression

Improve patients quality of life .

Target levels of blood pressure in patients with Diabetes

Target levels of blood pressure in patients with Diabetes

The UKPDS and the Hypertension Optimal Treatment

(HOT) trial both demonstrated improved outcomes ,

especially in preventing stroke, in patients assigned to

lower blood pressure targets.

A target blood pressure goal of <130/80 mmHg is

reasonable if it can be safely achieved <125/75 mmHg

(in proteinuria >0.5-1g/d)

It is very clear that many people will require more than

one drug to achieve the recommended target.

Non-drug management of Hypertension

Non-drug management of Hypertension

Moderate sodium restriction ,reduce salt intake from 200mmol

(4600 mg) to 100mmol (2300 mg) daily 5 mm fall in DBP.

Weight reduction (Loss of 1 kg weight decrease mean

arterial pressure of about 1 mm Hg.

Moderately intense physical activity: 30-45 mins of brisk

walking most days of the week has been shown to reduce BP.

Stop smoking decease micro, macrovasular Compilications

Role of very low calorie diets ?

Pharmacologic agents that induce weight loss?

Drug therapy of Hypertension in Diabetes

Drug therapy of Hypertension in Diabetes

There is strong evidence that pharmacological

therapy of hypertension in patients with diabetes

is effective in producing substantial decreases in

cardiovascular and micro vascular diseases.

It must be noted that many patients required more

than one drug to achieve the specified target

levels of blood pressure control.

The UKPDS-Hypertension in Diabetes Study showed

no significant difference in outcomes for treatment

based on an ACE inhibitor compared with a ß-blocker.

Drug therapy of Hypertension in Diabetes,cont

Drug therapy of Hypertension in Diabetes,cont

ACE inhibitors and ß-blockers appear to be superior to DCCBs therefore, DCCBs appear to be appropriate agents in addition to but not instead of ACE inhibitors , and ß-blockers .

The UKPDS-Hypertension in Diabetes Study showed

no significant difference in outcomes for treatment

based on an ACE inhibitor compared with a ß-blocker.

There are no long-term studies of the effect of ß -blockers, loop diuretics, or centrally acting adrenergic blockers on long-term complications of diabetes

A variety of trials have demonstrated that ACEIs / ARBs therapy should be considered the standard therapy to retard worsening albuminuria and subsequent renal disease.

In Addition to their proper BP control, ACE inhibitors can

retard the progression of microalbuminuria and can lower

the percentage of patient who progress to end-stage

renal disease and death.

All patients with asymptomatic or symptomatic heart failure due to left ventricular systolic dysfunction should receive an ACE inhibitor. Approximately 50% of patients post-MI have significant left ventricular dysfunction and could benefits from ACE inhibitor therapy.

Role of ACEIs & ARBs in DiabetesRole of ACEIs & ARBs in Diabetes

A meta-analysis of 20 published and two unpublished

trials was carried out to determine whether ACE inhibitors

could slow the progression of renal disease of varying

degree showed that treatment of chronic renal insufficiency

with ACE inhibitors delayed the progression of disease

compared with placebo.

ACE inhibitors have a favorable effect on cardiovascular

outcomes , this cardiovascular effect may be mediated by

mechanisms other than blood pressure reduction.

Role of ACEIs & ARBs in Diabetes,contRole of ACEIs & ARBs in Diabetes,cont

Role of ACEIs & ARBs in Diabetes ,contRole of ACEIs & ARBs in Diabetes ,cont

There are numerous studies documenting the effectiveness Of ACE inhibitors and ARBs in retarding the development and progression of diabetic complications : EUCLID Study (Lisinopril vs placebo) Type1 Diabetic retinopathy CALM study (Lisinopril vs Candestran & combination) BP & Microalbuminurea RENAAL study(Losartan vs placebo) Type 1 Diabetic nephropathy HOPE study (Ramiplil vs placebo) Reduction of MI,stroke ,CV death All- cause death in high risk pts esp DM. IDNT study (Irbesartan vs amlodipine vs placebo) MARVAL study (Valsartan) Type 2 Diabetic nephropathy Irbesartan & Valsartan delay nephropathy amlodipine no better than placebo

ACEIs Vs ARBsACEIs Vs ARBs

Angiotensinogen Other Substrates?

Angiotensin I

Angiotensin II

Bradykinin & other substrates

Psychological actionsActions?

AT2 AT1

Renin

ACE

Renin Blockade

ACE inhibitors

Angiotensin II receptor antagonists

blocking the Renin-Angiotensin

system

?

ACEIs Vs ARBsACEIs Vs ARBs

ACEIs Vs ARBsACEIs Vs ARBs

Evidence for beneficial outcomes (especially renal) with ARBs is growing but varying opinion on their optimal role.

Unfortunately, several ARB outcome trials have avoided a head-to-head comparison with ACEIs.

Losartan was not superior to captopril in patients with heart failure( ELITE II) , captopril reduced CV-death in post-MI patients more than losartan( OPTIMAAL) However, both of these studies found that less patients discontinued losartan due to adverse effects

ARBs are an alternative in patients who develop ACEI induced cough but are more expensive than most ACEIs

ACEI-ARB combinations show some promise for renal outcomes( CALM, COOPERATE), however they are expensive. 

Approach to Combination Therapy

The ABCD Approach

Approach to Combination Therapy

The ABCD Approach

A = ACEI or ARB B = β-blocker

C = CCB D = diuretic low-dose

If initial drug is A or B adding drug C or D

provides a synergistic effect.

If initial drug is C or D adding drug A or B

provides a synergistic effect; (C+diuretic, also option).

•Verapamil or diltiazem with a β-blocker negative effects on heart (e.g. ↓ heart rate and ↓ cardiac output)•CCBS and α-blockers potential for excessive hypotension; increased risk of falls, etc.

Thiazide like diuretic (low dose→HCT 12.5-25mg od)

B blocker (cardioselective-e.g. atenolol, metoprolol)

Long acting calcium channel blockers (amlodipine)

1st potion ACEIs

Monotherapy

Drug therapy in

Hypertension with Diabetes

Drug therapy in

Hypertension with Diabetes

2nd option ARBsOR

+ Combination

  

Summary

  

Summary

Non-pharmacological measures (particularlyweight loss

and reduction in salt intake) should be encouraged in all

patients with diabetes, independently of the existing

blood pressure.

The goal blood pressure to aim at during behavioural

or pharmacological therapy is below 130/80 mmHg.

To reach this goal, most often combination therapy

will be required.

It is recommended that all effective and well tolerated

antihypertensive agents are used, generally in combination.

In diabetic patients with high blood pressure, who

may sometimes achieve blood pressure goal

by monotherapy, the first drug to be tested should

be a blocker of the renin–angiotensinsystem

(ACE & ARBS)

The finding of microalbuminuria in type

1 or 2 diabetics is an indication for antihypertensive

treatment, especially by a blocker of the

renin–angiotensin system, irrespective of the blood

pressure values(normotesive Hypertension).

Summary,cont Summary,cont

DCCBs (compared with ACE inhibitors, ARBs,

ß-blockers, or diuretics) should be used as

second-line drugs for patients who cannot tolerate

the other preferred classes or who require additional

agents to achieve the target blood pressure.

Other classes, including Alph -blockers, may be

used under specific indications such as symptoms

of BPH.

Achievement of the target blood pressure goal with

a regimen that does not produce burdensome

side effects and is at reasonable cost to the patient

is probably more important than the specific drug strategy.

Summary,cont Summary,cont

Thank youThank you