EFFECTS OF DIPYRIDAMOLE IN COMBINATION WITH ANTICOAGULANT-THERAPY ON SURVIVAL AND THROMBOEMBOLIC EVENTS IN PATIENTS WITH PROSTHETIC HEART-VALVES - A METAANALYSIS OF THE RANDOMIZED TRIALS

The addition of dipyridamole, an antiplatelet agent, to conventional a nticoagulant regimens has been shown to reduce the frequency of emboli zation after valve replacement with a mechanical prosthesis. The purpo se of this meta-analysis was to reevaluate the benefit of dipyridamole by analyzing the evidence from all randomized clinical trials. Summar y data were extracted from the application to the Food and Drug Admini stration. Six randomized clinical trials had accrued 1141 patients, of whom 582 received anticoagulant therapy alone and 559 received additi onal dipyridamole at dosages ranging from 225 to 400 mg per day. The e vents analyzed were all thromboembolic events, both fatal and nonfatal ; hemorrhagic events, both fatal and nonfatal; and the overall mortali ty. The combination of dipyridamole with anticoagulants reduced the ri sk of thromboembolic events (fatal or nonfatal) by 56% when compared w ith the use of anticoagulants alone (p = 0.0001). The risk reduction w as seen in fatal and in nonfatal thromboembolic events (risk reduction for fatal events, 64%, p = 0.008; for nonfatal events, 50%, p = 0.005 ). The overall mortality rate was also significantly reduced by 40% in the group receiving dipyridamole (p 0.013). There was no difference b etween treatment groups with respect to hemorrhagic events (risk reduc tion, -1%, p = 0.94). This meta-analysis supports the use of dipyridam ole in this setting and warrants further trials with new antiplatelet agents.