Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial

Background The combination of fibrinolytic therapy and heparin for acute myocardial infarction fails to achieve reperfusion in 40–70% of patients, and early reocclusion occurs in a substantial number. We did a randomised, open-label trial to compare the thrombin-specific anticoagulant, bivalirudin, with heparin in patients undergoing fibrinolysis with streptokinase for acute myocardial infarction. Methods 17 073 patients with acute ST-elevation myocardial infarction were randomly assigned an intravenous bolus and 48-h infusion of either bivalirudin (n=8516) or heparin (n=8557), together with a standard 1.5 million unit dose of streptokinase given directly after the antithrombotic bolus. The primary endpoint was 30-day mortality. Secondary endpoints included reinfarction within 96 h and bleeding. Strokes and reinfarctions were adjudicated by independent committees who were unaware of treatment allocation. Analysis was by intention to treat. Findings By 30 days, 919 patients (10·8%) in the bivalirudin group and 931 (10·9%) in the heparin group had died (odds ratio 0·99 [95% CI 0·90–1·09], p=0·85). The mortality rates adjusted for baseline risk factors were 10·5% for bivalirudin and 10·9% for heparin (0·96 [0·86–1·07], p=0·46). There were significantly fewer reinfarctions within 96 h in the bivalirudin group than in the heparin group (0·70 [0·56–0·87], p=0·001). Severe bleeding occurred in 58 patients (0·7%) in the bivalirudin group versus 40 patients (0·5%) in the heparin group (p=0·07), and intracerebral bleeding occurred in 47 (0·6%) versus 32 (0·4%), respectively (p=0·09). The rates of moderate and mild bleeding were significantly higher in the bivalirudin group than the heparin group (1·32 [1·00–1·74], p=0·05; and 1·47 [1·34–1·62], p<0·0001; respectively). Transfusions were given to 118 patients (1·4%) in the bivalirudin group versus 95 patients (1·1%) in the heparin group (1·25 [0·95–1·64], p=0·11). Interpretation Bivalirudin did not reduce mortality compared with unfractionated heparin, but did reduce the rate of adjudicated reinfarction within 96 h by 30%. Small absolute increases were seen in mild and moderate bleeding in patients given bivalirudin. Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.