"Clopidogrel plus Aspirin versus Aspirin Alone in High-Risk Patients". The New England Journal of Medicine. 2006. 354(16):1706-1717. PubMed
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Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Funding 10 Further Reading
Does dual antiplatelet therapy with clopidogrel plus low-dose aspirin improve outcomes in a broad population of patients at high risk for atherothrombotic events compared to aspirin alone?
In a broad population of high-risk patients, dual antiplatelet therapy with clopidogrel plus low-dose aspirin did not significantly reduce the rate of myocardial infarction, stroke, or death from cardiovascular causes compared to aspirin alone. There was a suggestion of harm in patients with multiple risk factors and only a marginal benefit in patients with established cardiovascular disease.
Dual antiplatelet therapy with clopidogrel and aspirin had not been widely tested in patients at high risk for atherothrombotic events beyond those with acute coronary syndromes or undergoing angioplasty.
Current guidelines do not generally recommend dual antiplatelet therapy for a broad high-risk population outside specific indications like acute coronary syndrome or percutaneous coronary intervention.
- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial - N=15,603 - Clopidogrel (75 mg per day) plus low-dose aspirin (75-162 mg per day), n=7802 - Placebo plus low-dose aspirin (75-162 mg per day), n=7801 - Median follow-up: 28 months - Analysis: Intention-to-treat
- Inclusion Criteria: Patients 45 years or older with clinically evident cardiovascular disease or multiple atherothrombotic risk factors - Exclusion Criteria: Use of long-term oral antithrombotic medications or nonsteroidal antiinflammatory drugs; planned revascularization; established indications for clopidogrel therapy
Baseline Characteristics - Median age: 64 years, 29.8% female - Patients with established cardiovascular disease: over 75% - Patients with multiple atherothrombotic risk factors: remaining percentage
- Patients were randomized to either clopidogrel plus aspirin or placebo plus aspirin. - Standard therapy, including statins and ACE inhibitors, was administered at the discretion of the investigator.
- Primary Outcome: Composite of myocardial infarction, stroke, or death from cardiovascular causes - Clopidogrel: 6.8%, Placebo: 7.3% (RR 0.93; 95% CI, 0.83 to 1.05; P=0.22) - Secondary Outcomes: Composite of primary outcome or hospitalization for unstable angina, transient ischemic attack, or revascularization - Clopidogrel: 16.7%, Placebo: 17.9% (RR 0.92; 95% CI, 0.86 to 0.995; P=0.04) - Severe bleeding: Clopidogrel: 1.7%, Placebo: 1.3% (P=0.09) - Moderate bleeding: Clopidogrel: 2.1%, Placebo: 1.3% (P<0.001)
The trial was sponsored and funded by Sanofi-Aventis and Bristol-Myers Squibb. Dr. Topol was supported by grants from the National Institutes of Health.
Additional information on the CHARISMA trial and related research can be found in the New England Journal of Medicine and other peer-reviewed scientific journals.