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Clopidogrel Plus Aspirin Does Not Significantly Reduce the Rate of Myocardial Infarction, Stroke or Cardiovascular Death

March 20, 2006

By: Sahar Bedrood and Asher Kimchi M.D.

Cleveland, Ohio - Platelets have been shown to play a central role in atherothrombosis. Low dose aspirin can reduce ischemic outcomes by inhibiting the cyclooxygenase pathway. Clopidogrel inhibits platelet aggregation by inhibiting the binding of ADP to the platelet receptor and thereby inhibiting the consequent activation of the glycoprotein GPIIb/IIIa complex. A study by Dr. Deepak Bhatt et al from the Cleveland Clinic in Ohio was published in the March 14, 2006 issue of The New England Journal of Medicine indicating clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke or death from cardiovascular causes.

The study randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).

Overall, the study concluded that dual therapy with clopidogrel and aspirin does not significantly reduce the rate of myocardial infarction, stroke and cardiovascular death and thus should not be recommended as a preventative therapy for such disease processes.

The study was presented at an American College of Cardiology meeting in Atlanta.

Co-authors: Deepak L. Bhatt, M.D., Keith A.A. Fox, M.B., Ch.B., Werner Hacke, M.D., Peter B. Berger, M.D., Henry R. Black, M.D., William E. Boden, M.D., Patrice Cacoub, M.D., Eric A. Cohen, M.D., Mark A. Creager, M.D., J. Donald Easton, M.D., Marcus D. Flather, M.D., Steven M. Haffner, M.D., Christian W. Hamm, M.D., Graeme J. Hankey, M.D., S. Claiborne Johnston, M.D., Koon-Hou Mak, M.D., Jean-Louis Mas, M.D., Gilles Montalescot, M.D., Ph.D., Thomas A. Pearson, M.D., P. Gabriel Steg, M.D., Steven R. Steinhubl, M.D., Michael A. Weber, M.D., Danielle M. Brennan, M.S., Liz Fabry-Ribaudo, M.S.N., R.N., Joan Booth, R.N., Eric J. Topol, M.D., for the CHARISMA Investigators


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