Don't add aspirin to warfarin therapy except with mechanical heart valve
Clinical QuestionIs the addition of aspirin to warfarin safe and more effective than warfarin alone?
Bottom LineExcept for patients with mechanical heart valves, the addition of aspirin to therapeutic warfarin doses does not decrease the risk of death or of thromboembolism and does not increase the risk of a major bleed. (LOE = 1a)
ReferenceDentali F, Douketis JD, Lim W, Crowther M. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease. A meta-analysis of randomized trials. Arch Intern Med 2007;167:117-124. [PMID:17242311]
Study DesignMeta-analysis (randomized controlled trials)
SynopsisThe researchers conducting this study assembled and combined randomized studies of at least 3 months' duration that compared warfarin plus aspirin with warfarin alone, in which warfarin was administered to achieve the same target international normalized ratio (INR) or was given at the same fixed dose in both treatment arms. The authors conducted an appropriate search of 3 databases, reviewed reference lists, and contacted experts to find 10 studies of more than 4000 patients that met their criteria. Two authors independently evaluated the research using a modified version of the Jadad criteria and extracted the data. Five studies evaluated the use of the combination in patients with mechanical heart valves, and the other studies included patients with atrial fibrillation, with coronary artery disease, or at high risk for cardiovascular disease. Doses of aspirin ranged from less than 100 mg to 1000 mg per day; warfarin was dosed to obtain a target INR of at least 1.8 in 8 studies and 2.0 or higher in 2 studies. Overall, major bleeding was more likely to occur when the combination was used (number needed to treat to harm = 100). Mortality due to any cause was not reduced by the addition of aspirin. In patients with mechanical heart valves, the addition of aspirin decreased the risk of thromboembolism (odds ratio = .27; 95% CI .15 - .49), but also increased the risk of bleeding. In patients with heart disease or atrial fibrillation, the addition of aspirin did not decrease the risk for thromboembolism but also did not increase the risk of major bleeding. There was no evidence of publication bias and the result showed homogeneity among the studies.
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