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Aspirin dose and cardioprotection
What is the best dose of aspirin for patients taking dual therapy with clopidogrel to prevent cardiovascular events? Investigators looked at 15,595 patients with cardiovascular disease or multiple risk factors in an observational analysis from a double-blind, placebo-controlled randomized trial. Patients were randomized to doses of aspirin less than 100 mg (75 mg or 81 mg), 100 mg, or greater than 100 mg (150 mg or 162 mg) with or without clopidogrel. The primary efficacy outcome was the composite of myocardial infarction, stroke, or cardiovascular death and the primary safety endpoint was severe life-threatening bleeding. In patients given aspirin alone, the hazard ratio for the efficacy and safety endpoints were the same regardless of aspirin dose. In patients given aspirin with clopidogrel, there was a statistically nonsignificant associated reduction in efficacy with aspirin doses over 100 mg, and a significantly higher increase in harm (hazard ratio, 1.30 with clopidogrel plus aspirin greater than 100 mg). The authors conclude that daily doses of aspirin greater than 100 mg were not associated with benefit and may be associated with harm in patients also taking clopidogrel. Therefore, daily doses of aspirin 75-81 mg optimize efficacy and safety in patients requiring long-term aspirin therapy, especially in patients receiving dual antiplatelet therapy (Ann Intern Med 2009;150:379-386). This is especially important given the recent U.S. Preventive Services Task Force recommendation that encourages men ages 45-79 years to take aspirin preventively when the potential benefit of a reduction of myocardial infarction outweighs the potential harm of an increase in gastrointestinal hemorrhage. Women ages 55-79 years are also encouraged to use aspirin when the potential benefit of a reduction in ischemic stroke outweighs the potential harm of increased gastrointestinal hemorrhage (Ann Intern Med 2009;150:396-404).