Abstract 3082: Clopidogrel Improves Cardiovascular Outcomes in Patients with Coronary Disease: A Meta-Analysis of Randomized Trials
Introduction: Large randomized controlled trials have evaluated the use of clopidogrel in addition to standard aspirin therapy in patients with coronary disease. While this approach reduces composite outcomes, the magnitude of benefit or harm on individual outcomes is unknown.
Hypothesis: We sought to determine if clopidogrel reduces the individual cardiovascular outcomes of death, myocardial infarction or stroke while increasing bleeds in patients with coronary artery disease.
Methods: We conducted a meta-analysis on all available studies that compared aspirin plus clopidogrel to aspirin plus placebo for the treatment of coronary artery disease. MEDLINE and Cochrane databases were searched for randomized clinical trials in English language from 1996 to 2006.
Results: This analysis included 5 randomized controlled trials (CURE, CREDO, CLARITY, COMMIT, and CHARISMA) in 76,642 patients, with 81% of the study population represented by an unstable coronary syndrome. Clopidogrel was given as a 300mg loading dose followed by 75mg daily in all trials except COMMIT and CHARISMA where no loading dose was given. Over the extent of follow-up the incidence of all cause mortality was 6.3% in the aspirin plus clopidogrel group versus 6.7% in the aspirin plus placebo group (RR = 0.94, 95% CI 0.89 to 0.99, p = 0.026). Similarly, the incidence of cardiovascular mortality was 5.7% and 6.0% (RR = 0.95, 95% CI 0.89 to 1.00, p = 0.048), myocardial infarction was 2.7% and 3.3% (RR = 0.83, 95% CI 0.76 to 0.89, p < 0.0001), and stroke was 1.2% and 1.4% (RR = 0.82, 95% CI 0.73 to 0.93, p = 0.002). Similarly, the incidence of major bleeding was 1.6% and 1.3% (RR =1.25, 95% CI 1.11 to1.40, p < 0.0001), fatal bleeding was 0.28% and 0.27% (RR = 1.04, 95% CI 0.79 to 1.35, p = 0.79), and hemorrhagic strokes was 0.24% and 0.25% (RR = 0.97, 95% CI 0.73 to 1.28, p = 0.82).
Conclusion: The addition of clopidogrel to aspirin significantly reduces all cause mortality, cardiovascular mortality, myocardial infarction, or stroke in patients with coronary disease. Major bleeding is increased, although there is not an excess of fatal or hemorrhagic bleeding.