Direct Comparison of Aspirin Plus Hirudin, Aspirin Plus Heparin, and Aspirin Alone Among 12,000 Patients with Acute Myocardial Infarction Not Receiving Thrombolysis: Rationale and Design of the First American Study of Infarct Survival (ASIS-1).

While antithrombotic therapy of acute myocardial infarction is clearly beneficial, substantial controversy exists regarding the optimal regimen. In particular, while aspirin alone has proven highly effective in reducing rates of reinfarction, stroke, and death following acute coronary occlusion, heparin has not clearly been shown to have additional benefit when added to aspirin but is associated with increased rates of hemorrhagic stroke and major bleeding. At the same time, available data for newer specific thrombin inhibitors such as hirudin suggest greater benefits than aspirin alone or aspirin plus heparin in terms of maintaining coronary flow, but possibly higher risks of hemorrhagic stroke and major bleeding. Since no completed or ongoing large-scale clinical trial has directly compared aspirin plus hirudin, aspirin plus heparin, and aspirin alone, it is not currently possible to decide which of these three antithrombotic regimens provides the optimal bmefit-to-risk ratio. The First American Study of Infarct Survival (ASIS-1) is directly comparing aspirin alone, aspirin plus heparin, and aspirin plus hirudin among 12,000 patients presenting with signs and symptoms of acute myocardial infarction who are not felt by their responsible physicians to be appropriate candidates for thrombolytic therapy. Such patients comprise almost two thirds of all U.S. subjects presenting with acute myocardial infarction and are a group at substantial risk of death, reinfarction, and stroke. Thus, the ASIS-I trial will provide importantly relevant data regarding the optimal antithrombotic regimen for the majority of patients presenting with acute myocardial infarction. In this manuscript we provide the rationale and design for the First American Study of Infarct Survival (ASIS-1), a randomized, double-blind, placebo-controlled trial directly comparing aspirin alone, aspirin plus intravenous heparin, and aspirin plus intravenous hirudin in the treatment of acute myocardial infarction patients not receiving thrombolytic therapy.