COMBINATION HEMOTHERAPY AND MORTALITY PREVENTION (CHAMP) STUDY RATIONALE AND DESIGN

It is now agreed that the majority of acute myocardial infarctions res ult from intracoronary thrombosis at sites of atherosclerotic plaque t hat have been disrupted. In 1947 Nicol and Fassett published the first clinical paper suggesting that agents interfering with blood coagulat ion could prevent myocardial infarction in patients at risk. Scores of subsequent clinical trials were performed to assess the efficacy of a nticoagulants and antiplatelet agents in preventing death and reinfarc tion in survivors of acute myocardial infarction. Despite these effort s no agreement exists on whether these strategies are beneficial and, if so, which is superior, The primary obstacle to progress in this fie ld has been the failure of nearly all trials to enroll the large numbe rs of subjects required to demonstrate a survival benefit. The large s ample size requirement derives from two inescapable facts: mortality r ates following acute infarction, though variable, are generally low an d the potential benefit of these agents in preventing mortality is sma ll. Combining oral anticoagulants with antiplatelet agents (combinatio n hemotherapy) may significantly enhance their antithrombotic effect. Clinical trials of combination hemotherapy have demonstrated superiori ty over anticoagulant monotherapy in the setting of stroke prevention in patients with prosthetic heart valves. Similar benefit was not obse rved in trials studying stroke prevention in nonvalvular atrial fibril lation and vascular morbidity in patients surviving an acute myocardia l infarction. The failure of these latter studies may relate to the pa rticularly low intensity of warfarin administered in combination with aspirin. This trial proposes to demonstrate that the combination of or al anticoagulation, administered in a moderate dose intensity, and ant iplatelet therapy is superior to aspirin monotherapy in reducing overa ll mortality following acute myocardial infarction.