Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in patients with acute myocardial infarction. The Ridogrel Versus Aspirin Patency Trial (RAPT).
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BACKGROUND
Aspirin, by nonselectively blocking cyclooxygenase both in platelets and in endothelial cells, not only inhibits the thromboxane A2 pathway of platelet activation but at the same time also the generation of vasodilating and platelet-inhibitory prostanoids, such as prostacyclin, by the endothelial cells. Ridogrel, by inhibiting thromboxane A2 synthase and blocking the thromboxane A2/prostaglandin endoperoxide receptors, is a more potent antiplatelet agent than aspirin and might offer an advantage over aspirin as an adjunct to thrombolysis. This study was performed to compare the efficacy and safety of ridogrel with that of aspirin as conjunctive therapy for thrombolysis in patients with acute myocardial infarction.
RESULTS
A total of 907 patients with acute myocardial infarction were randomized between aspirin and ridogrel given in addition to streptokinase (1.5 MU over a period of 1 hour). The primary end point was coronary patency (TIMI flow grades 2 and 3) at predischarge angiography to be performed between 7 and 14 days after admission. A patent infarct-related vessel was found in similar proportions of patients in the two treatment groups: 72.2% in the ridogrel and 75.5% in the aspirin group. The presence of clinical markers of reperfusion at 2 hours and the incidence of major clinical events during hospital stay were also similar in both groups. However, in a post hoc analysis, a lower incidence of new ischemic events (reinfarction, recurrent angina, ischemic stroke) was observed with ridogrel: 13% versus 19% in the aspirin group (a 32% reduction; P < .025). No excess of serious bleeding complications, including hemorrhagic stroke, was found.
CONCLUSIONS
Ridogrel is not superior to aspirin in enhancing the fibrinolytic efficacy of streptokinase but might be more effective in preventing new ischemic events.
