Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: A meta-analysis of randomized trials

Thomas J. Helton, Anthony A. Bavry, Dharam J. Kumbhani, Sandeep Duggal, Henri Roukoz, Deepak L. Bhatt

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58 Scopus citations


Objectives: To quantify the impact of clopidogrel plus aspirin on the individual outcomes of death, myocardial infarction, or stroke in patients with established cardiovascular disease, or in patients with multiple risk factors for vascular disease. Background: Randomized trials have demonstrated a reduction in composite outcomes when clopidogrel is added to aspirin therapy in patients with coronary artery disease; however, the magnitude of benefit on individual outcomes is unknown. Methods: We conducted a meta-analysis on randomized, controlled trials that compared aspirin plus clopidogrel with aspirin plus placebo for the treatment of coronary artery disease. Results: This analysis included five randomized trials (CURE, CREDO, CLARITY, COMMIT, and CHARISMA) in 79 624 patients. The incidence of all-cause mortality was 6.3% in the aspirin plus clopidogrel group versus 6.7% in the aspirin group (odds ratio [OR] 0.94; 95% CI 0.89, 0.99; p = 0.026). The incidence of myocardial infarction was 2.7% and 3.3% (OR 0.82; 95% CI 0.75, 0.89; p < 0.0001), and stroke was 1.2% and 1.4% (OR 0.82; 95% CI 0.73, 0.93; p = 0.002). Similarly, the incidence of major bleeding was 1.6% and 1.3% (OR 1.26; 95% CI 1.11, 1.41; p < 0.0001), and fatal bleeding was 0.28% and 0.27% (OR 1.04; 95% CI 0.76, 1.43; p = 0.79). Conclusion: The addition of clopidogrel to aspirin results in a small reduction in all-cause mortality in patients with ST-elevation myocardial infarction and a modest reduction in myocardial infarction and stroke in patients with cardiovascular disease. The overall incidence of major bleeding however is increased, although there is no excess of fatal bleeds or hemorrhagic strokes.

Original languageEnglish (US)
Pages (from-to)289-297
Number of pages9
JournalAmerican Journal of Cardiovascular Drugs
Issue number4
StatePublished - 2007
Externally publishedYes

Bibliographical note

Funding Information:
Dr Bhatt was the primary investigator for the CHARISMA study and received research grants from both Bristol Myers Squib (New York, USA) and Sanofi Aventis (Paris, France). He was also the co-primary investigator on the LANCELOT and CHAMPION studies and received research grants from Eisai (Woodcliff Lake, NJ, USA) and The Medicines Company (Parsippany, NJ, USA), respectively. All research grant funds were given directly to the institution (Cleveland Clinic) and not to Dr Bhatt personally, for the above studies.


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