Randomized Trial of Low Molecular Weight Heparin (Dalteparin) in Prevention of Left Ventricular Thrombus Formation and Arterial Embolism After Acute Anterior Myocardial Infarction: The Fragmin in Acute Myocardial Infarction (FRAMI) Study

Abstract

Objectives. The present trial investigated the efficacy and safety of dalteparin in the prevention of arterial thromboembolism after an acute anterior myocardial infarction (MI).Background. Left ventricular (LV) thrombus formation is associated with increased risk of arterial embolism in patients with an acute MI. Thrombolytic and antiplatelet therapy do not prevent thrombus formation.Methods. A total of 776 patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of subcutaneous dalteparin (150 IU/kg body weight every 12 h during the hospital period). Thrombolytic therapy and aspirin were administered in 91.5% and 97.6% of patients, respectively. The primary study end point was the composite of thrombus formation diagnosed by echocardiography and arterial embolism on day 9 ± 2.Results. Of 517 patients with echocardiographic recordings available for end point analysis, thrombus formation or embolism, or both, was found in 59 (21.9%) of 270 patients (59 with thrombus, none with embolism) in the placebo group and 35 (14.2%) of 247 patients (34 with thrombus, 1 with embolism) in the dalteparin group (p = 0.03). The risk reduction of thrombus formation associated with dalteparin treatment was 0.63 (95% confidence interval 0.43 to 0.92, p = 0.02). Analyses of all randomized patients (388 in each group) revealed no significant difference between the placebo and dalteparin groups with respect to arterial embolism (6 vs. 5 patients), reinfarction (8 vs. 6 patients) and mortality rates (23 vs. 23 patients, p = NS for all). Dalteparin was associated with an increased risk of hemorrhage: major in 11 dalteparin group patients (2.9%) versus 1 placebo group patient (0.3%, p = 0.006); minor in 52 dalteparin group patients (14.8%) versus 8 placebo group patients (1.8%, p < 0.001).Conclusions. Dalteparin treatment significantly reduces LV thrombus formation in acute anterior MI but is associated with increased hemorrhagic risk.