Cost-Effectiveness of Clopidogrel in Patients with Acute Coronary Syndrome
Speaker: William S. Weintraub, MD, Professor of Medicine, Division of Cardiology, Department of Medicine and Chief, Emory Center for Outcomes Research, Emory University School of Medicine, Atlanta, Georgia.
Clopidogrel (Sanofi-Synthelabo/Bristol-Myers Squibb) has been found to be both efficacious and cost-effective over the long term in patients who have undergone percutaneous coronary intervention (PCI) early after non-ST-segment elevation acute coronary syndrome (ACS).
Results from the Percutaneous Coronary Inter-vention-Clopidogrel in unstable Angina to Prevent Recurrent Ischemic .Events (PCI-CURE) study demonstrated the benefits of clopidogrel, when added to aspirin, up to one year after PCI following ACS. An analysis was carried out to evaluate the cost-effectiveness in platelet inhibition for up to one year after PCI, during the initial hospitalization in the PCI-CURE trial. After PCI, more than 80% of the patients received the open-label, adenosine diphosphate (ADP)-receptor antagonist for four weeks, followed by the study drug for up to one year.
This PCI-CURE subgroup characterizes PCI practice patterns in the U.S. The composite of cardiovascular death, stroke, or myocardial infarction (MI) occurred in 9.3% of patients (76) receiving clopidogrel and in 12.8% of patients (116) receiving placebo, resulting in a 27% reduction in risk that favored clo-pidogrel.
Hospitalized patients were assigned to a Diagnosis-Related Group (DRG). Costs were estimated from Medicare’s average reimbursement, MEDSTAT private insurance, and a blend of MEDSTAT for those younger than 65 years of age and Medicare for those older than age 65. Clopidogrel canadian was assigned an average wholesale cost of $3.22 per day. Life expectancy losses associated with death, nonfatal MI, and nonfatal stroke were
estimated from published data from the Framingham study, which were discounted 3%, and from the Saskatchewan Health Database.
The incremental cost-effectiveness ratio was $935 per life-year gained with clopidogrel in the PCI-CURE study. This compared with other reported cost-effectiveness ratios or cardiovascular interventions, for example:
- $220 per life-year gained for smoking cessation after an MI
- $2,080 per life-year gained for treatment with the angio-tensin-converting enzyme (ACE)-inhibitor (Prinivil®, Merck) after an MI
- $21,200 per life-year gained for thrombolytic therapy in the elderly
- $5,400-$32,000 per life-year gained for treatment with statins
In conclusion, the results for clopidogrel are robust, as confirmed by various costing strategies and estimates of the effects of events on long-term survival.
Intensive Statin Therapy After Acute Coronary Syndrome
Speaker: Christopher P. Cannon, MD, Associate Professor of Medicine, Harvard Medical School, and Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.
Patients with a recent episode of ACS derived greater protection against death or major cardiovascular events when they received an early, continuous, intensive lipid-lowering statin regimen instead of standard-dose statin therapy.
These landmark results came from the Ator-rastatin Evaluation and Infarction Therapy-Thrombolysis in Myocardial Infarction 22 trial (PROVE IT-TIMI 22). This large-scale, international study included 4,162 patients who had been hospitalized because of an ACS within the preceding 10 days. The patients had a total cholesterol count of 240 mg/dl or less upon hospital entry or up to six months earlier.
The patients were enrolled at 349 hospital sites in eight countries. Of these patients, 2,099 were randomly assigned to receive intensive therapy with atorvastatin (Pfizer) 80 mg daily; 2,063 received standard statin therapy with pravastatin (Bristol-Myers Squibb) 40 mg daily, along with standard medical and interventional treatment for ACS, including aspirin 75-325 mg daily with or without clopidogrel (Plavix®) or canadian warfarin (DuPont). Patients were observed at 30 days, at four months, and every four months thereafter for 18 to 36 months. Follow-up observation lasted for approximately 24 months. The primary endpoint of the study was the composite of all-cause mortality, MI, and documented unstable angina requiring rehospitalization, revascularization, or stroke.
The median baseline low-density lipoprotein-cholesterol (LDL-C) level in both treatment groups was 106 mg/dl. During follow-up, the group receiving the standard dose of prava-statin achieved LDL-C levels of 95 mg/dl; the group receiving the intensive dose achieved levels of 62 mg/dl. Among the 75% of patients who had not previously received statin therapy within 30 days, the median LDL-C levels had fallen by 22% in the pravastatin group and by 51% in the ator-vastatin group.
The more intensive canadian atorvastatin therapy was associated with a 16% reduction in the risk of all-cause mortality or major cardiovascular events, compared with the present standard treatment with regular-dose pravastatin. After two years, the incidence of cardiovascular events was 26.3% for the standard-dose pravastatin drug group and 22.4% for the high-dose atorvastatin group. The relative risk reduction of all-cause mortality alone was even greater (28%) with intensive statin therapy, the advantages of which began as early as 30 days after initiation and continued for two years.