THE POWER OF CLINICAL PRACTICE GUIDELINES Cost Effective
Medicine By Dr. Akhtar Husain Associate Professor
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CONCERNS Health care is fast becoming unaffordable Payers are
demanding more accountability Value for money spent is replacing
quality at any cost Variations in the provision of health care is
morally unacceptable 47 million uninsured in USA Medical errors
must be minimized and patient safety maximized
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Management of AMI 1970s:Morphine, Oxygen, 4-6 weeks
hospitalization. CURRENT: Reduction of infarct size by various
interventions. FUTURE: Pharmacogenics, newer imaging modalities,
Cell therapy-induced regeneration.
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CURRENT PRACTICE Marvelous imaging techniques Newer drugs
Interventions Intracardiac pacers-defibrillators
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DR. ALFRED BOVE President of ACC I HAVE NOT WITNESSED SUCH
DISDAIN AS OUR OWN GOVERNMENT EXPRESSES FOR CARDIOLOGISTS, NOR HAVE
I WITNESSED SUCH ANIMOSITY AMONG MEDICAL SPECIALTIES. THIS DISDAIN
SEEMS TO COME FROM CONCERNS ABOUT COST
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Expressed as $$$ amount / QALY (quality adjusted life
year)
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GUSTO TRIAL 40000 randomized patients tPA vs Streptokinase: Net
0.9% reduction of mortality (p=0.001). Suppose average survival: 10
years? $2000 / 0.9= 2222x100=222,200 222200/10=$22,220/QALY
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Cost effective therapy InterventionGroupCost/QALYEvidence
SimvastatinIHD-Men$5400SSSS+proj SimvastatinIHD- Women
$10500SSSS+proj AbsciximabHigh risk PTCA $5500EPIC+mod tPa vs
Streptokin. AMI32700GUSTO+pr Imp. Defib.SD risk37000Model
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Figure 3 Absolute Versus Incremental CE
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Cost effectiveness in Medicare population Mammographic
screening $ 10-25K Colon cancer screening $ 10-25 K Osteoporosis
screening $ 10-25 K Dialysis in ESRD $ 50-100 K Beta blocker after
MI < $ 10 K Chol. Management $ 10-50 K AICD $ 30-85 K LV assist
device $ 500K- !.4 mill
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Mammogram controversy Age 40-49 years: 1900 have to be screened
for a decade to save 1 life 50-59: 1300 60-69: 377 Cost: $200 per
study 40-49: 200x1900=380000x10=3.8 mill Problems: imaging, biopsy,
inappropriate therapy & anxiety
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Quality at any cost versus Cost effective medicine
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WHAT IS COST EFFECTIVE? USA: $50000-100000 per QALY UK: #30000
sterling (enforced) SAUDI ARABIA: SR 200k or 100k or 50k ? The
government has to decide and enforce. INDIVIDUAL: variable
according to social status. (eg: SR 4000/year for clopidogrel)
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Ranking by GDP per capita RANKCOUNTRYGDP per capita
1Lichtenstein$118,000 2Qatar&111,000 3Luxembourg$81,200
4Bermuda$69,900 5Norway$59,500 6Kuwait$57,500 7Jersey$57,000
8Singapore$51,600 9Brunei$51,300 10USA$46,500
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GDP per capita (cont) UNITED ARAB Emirates #12 44,600 BAHRAIN
#28 37,400 ISRAEL #48 28,600 SAUDI ARABIA #60 20,500 OMAN #61
20,200 MALAYSIA #75 15,200 IRAN #87 12,800 TURKEY #92 11,900
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DRUG COMPANIES Drug companies want to maximize profits.
Physicians are the conduit. Pharm. Industry spends $ 13 billions
annually on gifts and payments. Provide 70% of the funding of
clinical trials. Provide 50% of the cost of CME
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DRUG COMPANY CEO TOTAL COMPENSATION2006 Wyeth $32.8 million
Johnson & Johnson $28.5 million Abbot Laboratories $26.9
million Pfizer Inc. $19.4 million Eli Lilly and Co. $15.2 million
Merck & Co., Inc. $10.2 million Bristol-Myers Squibb Co. $ 9.7
million
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Legal Settlements Lupron case(TAP): $ 290 million in criminal
fines +$ 585 million civil penalties Zoladex(Astra Zeneca): $355
million Schering-Plough:$350 million for physician kickbacks Eli
Lilly: $ 1.4 billion
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Conflict of Interest Research: plan, analysis of data, writing,
publication, withholding negative results High consultant fees for
researchers and guideline authors 87% of authors have relationship
with industry Prescription data-mining: AMA earned $44 million in
one year(16% of its budget)
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Dual Antiplatelet Therapy Stable angina pectoris: Not indicated
UA/NSTEMI: For one year STEMI: For one year PCI: BMS for one month
& DES for one year
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Class I Benefit >>> Risk Procedure/ Treatment SHOULD
be performed/ administered Class IIa Benefit >> Risk
Additional studies with focused objectives needed IT IS REASONABLE
to perform procedure/administer treatment Class IIb Benefit Risk
Additional studies with broad objectives needed; Additional
registry data would be helpful Procedure/Treatment MAY BE
CONSIDERED Class III Risk Benefit No additional studies needed
Procedure/Treatment should NOT be performed/administered SINCE IT
IS NOT HELPFUL AND MAY BE HARMFUL Applying Classification of
Recommendations and Level of Evidence Level A: Recommendation based
on evidence from multiple randomized trials or meta-analyses
Multiple (3-5) population risk strata evaluated; General
consistency of direction and magnitude of effect Level B:
Recommendation based on evidence from a single randomized trial or
non-randomized studies Limited (2-3) population risk strata
evaluated Level C: Recommendation based on expert opinion, case
studies, or standard-of-care Very limited (1-2) population risk
strata evaluated
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Class I 1. Clopidogrel 75 mg per day orally should be added to
aspirin in patients with STEMI regardless of whether they undergo
reperfusion with fibrinolytic therapy or do not receive reperfusion
therapy. (Level of Evidence: A) Treatment with clopidogrel should
continue for at least 14 days. (Level of Evidence: B)
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Class IIa 1. In patients less than 75 years of age who receive
fibrinolytic therapy or who do not receive reperfusion therapy, it
is reasonable to administer an oral loading dose of clopidogrel 300
mg. (Level of Evidence: C) (No data are available to guide decision
making regarding an oral loading dose in patients 75 years of age
or older.) 2. Long-term maintenance therapy (e.g., 1 year) with
clopidogrel (75 mg per day orally) is reasonable in STEMI patients
regardless of whether they undergo reperfusion with fibrinolytic
therapy or do not receive reperfusion therapy. (Level of Evidence:
C)
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Antiplatelet Therapy Aspirin should be administered to
UA/NSTEMI patients as soon as possible after hospital presentation
and continued indefinitely in patients not known to be intolerant
of that medication. (Box A) Clopidogrel (loading dose [LD] followed
by daily maintenance dose)* should be administered to UA/NSTEMI
patients who are unable to take ASA because of hypersensitivity or
major gastrointestinal intolerance. (Box A) *Some uncertainty
exists about optimum dosing of clopidogrel. Randomized trials
establishing its efficacy and providing data on bleeding risks used
a loading dose of 300 mg orally followed by a daily oral
maintenance dose of 75 mg. Higher oral loading doses such as 600 or
900 mg of clopidogrel more rapidly inhibit platelet aggregation and
achieve a higher absolute level of inhibition of platelet
aggregation, but the additive clinical efficacy and the safety of
higher oral loading doses have not been rigorously established. LD
added
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Antiplatelet Therapy In UA/NSTEMI patients with a history of
gastrointestinal bleeding, when ASA and clopidogrel are
administered alone or in combination, drugs to minimize the risk of
recurrent gastrointestinal bleeding (e.g., proton- pump inhibitors)
should be prescribed concomitantly. New
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Clopidogrel in Unstable angina to prevent Recurrent ischemic
Events (CURE) 12,562 patients within 24 h UA/NSTEMI Placebo vs
clopidogrel (LD 300 mg 75 mg qd) Other meds: ASA CV death, MI, or
stroke, rate of recurrent ischemia & revasc with clopidogrel
Major (nonlife-threatening) bleeding with clopidogrel No routine
inv strategy, 23% revasc during initial admission Although well
tolerated, < 10% GP IIb/IIIa + ASA + clopidogrel + heparin use
in study patients Yusuf S, et al. N Engl J Med
2001;345:494502.
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Initial Conservative Strategy: Antiplatelet Therapy For
UA/NSTEMI patients in whom an initial conservative (i.e.,
noninvasive) strategy is selected, clopidogrel (loading dose
followed by daily maintenance dose)* should be added to ASA and
anticoagulant therapy as soon as possible after admission and
administered for at least 1 month (Level of Evidence: A) and
ideally up to 1 year. (Level of Evidence: B) (Box C2) *Some
uncertainty exists about optimum dosing of clopidogrel. Randomized
trials establishing its efficacy and providing data on bleeding
risks used a loading dose of 300 mg orally followed by a daily oral
maintenance dose of 75 mg. Higher oral loading doses such as 600 or
900 mg of clopidogrel more rapidly inhibit platelet aggregation and
achieve a higher absolute level of inhibition of platelet
aggregation, but the additive clinical efficacy and the safety of
higher oral loading doses have not been rigorously
established.
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NUMBERS NEEDED TO TREAT CLARITY-TIMI 28 40 Patients COMMIT/CCS2
111 Patients CURE 100 Patients Cost of Clopidogrel: SR 4000 SR
400000 per event (death,MI,stroke refractory ischemia)
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CURE TRIAL PatientsAntiplatelet treatment Results 12,562
patients with ACS with follow up of one year Clopidogrel+ ASA vs
placebo+ASA 20% relative risk reduction of MACE (p=0.001)
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PRACTICE VARIATION There may be a ten fold variation in stress
imaging and coronary revascularization. No correlation between
cardiovascular spending and CV health. There is waste, uncertainty,
inefficiency and poor performance
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Comparative Effectiveness Research Atorvastatin vs simvastatin
Antiarrhythmics vs defibrillators Stents vs CABG surgery Medical
therapy vs revascularization Costs and benefits
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Criticism of Trials Underpowered trials. Unknown effects of
polypharmacy. Decision to change a trial in progress The short
follow up. The choice of arbitrary end points. Use of surrogate end
points.
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Criticism of Trials (cont) The practice of post-trial subgroup
analysis. The unsupported claims of class effects. The gap between
statistical and clinical significance. The implications of
publication bias. The consequence of conflict of interest
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STROKE IN 5 YEARS HTNControl group Treated group Relative RR
Absolute RR NNT Moderate
