A Comparison between Heparin and Low-Dose Aspirin as Adjunctive Therapy with Tissue Plasminogen Activator for Acute Myocardial Infarction

Abstract

We report the results of the Heparin—Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P<0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups. Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy. (N Engl J Med 1990; 323:1433–7.) THROMBOLYTIC therapy administered early after the onset of acute myocardial infarction has been shown to decrease infarct size, improve ventricular function, and reduce early mortality.123 Nevertheless, several issues remain unresolved, including the occurrence of acute coronary-artery reocclusion and reinfarction after successful thrombolysis and the hemorrhagic risk associated with reperfusion strategies.1234567 Until recently, clinical trials have generally combined the use of thrombolytic agents, particularly recombinant tissue plasminogen activator (rt-PA) with early intravenous heparin.1234,7 Heparin has been proposed to enhance initial thrombolysis and maintain coronary-artery patency after the administration of rt-PA,3,8 but it is also suspected to increase the frequency of bleeding. © 1990, Massachusetts Medical Society. All rights reserved.