Bleeding Complications and INR Control of Combined Warfarin and Low-Dose Aspirin Therapy in Patients with Unstable Angina and Non-Q-Wave Myocardial Infarction.

Abstract

The purpose of this study was to compare bleeding complications in patients with non-Q-wave myocardial infarction and unstable angina receiving combination therapy with aspirin plus warfarin versus aspirin alone. A post-hoc analysis was performed on patients enrolled in the Antithrombotic Therapy in Acute Coronary Syndrome (ACTACS) study, which was a prospective, randomized, multicenter trial of antithrombotic therapy in unstable angina or non-Q-wave myocardial infarction. A total of 358 patients admitted within 48 hours of chest pain were randomized to antithrombotic therapy with either (1) aspirin alone or (2) aspirin (162.5 mg) plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Major and minor bleeding episodes, hemoglobin levels, and prothrombin times or INR levels were prospectively recorded. Major bleeding episodes were subclassified as relating to CABG/PTCA or not. The rate of major bleeding complications not associated with CABG or PTCA was 2.0%, and did not differ between therapy assignments. Among 55 patients undergoing CABG, 29 (53%) required transfusion of two or more units of blood. Minor bleeding was also infrequent (2.8%). All patients with minor bleeding had a full clinical recovery, and only one patient with a major bleed resulted in minor disability. Warfarin was well managed, with 50% of INRs falling between 1.9 and 2.7. Combination therapy with low-dose aspirin and warfarin (INR mean 2.5) produces an insignificant rise in the incidence of major and minor bleeding. These events are infrequent and do not usually result in major disability. The effect of longer duration combination therapy remains to be determined.