Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis

OBJECTIVES The objective of this study was to compare the effectiveness and safety of adding dipyridamole or aspirin to warfarin among patients with prosthetic heart valves using meta-analytic techniques. BACKGROUND Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimize this risk. An important issue is the effectiveness and safety of the latter strategy. METHODS A combined MEDLINE and manual search was made for relevant articles from 1966 to November 1999. Standard meta-analysis techniques were used. RESULTS Ten studies involving 2,199 subjects met the inclusion criteria. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio [OR]: 0.41, p < 0.001) and total mortality (OR: 0.49, p < 0.001). The risk of major bleeding was increased when antiplatelet agents were added (OR: 1.50, P = 0.033). For major bleeding, the comparison of trials performed before and after 1990 (OR: 2.23 and 0.88, respectively) showed that the chi-square test for heterogeneity was significant (p = 0.025). The latter trials used low-dose aspirin, suggesting that the risk of bleeding may be lower with contemporary low-dose (100 mg daily) aspirin. CONCLUSIONS Adding antiplatelet therapy, especially low-dose aspirin, to warfarin decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is slightly increased with antiplatelet therapy. Nonetheless, the risk of bleeding appears to have diminished with the lower doses of aspirin used in the more recent trials, resulting in a favorable risk-to-benefit profile.