Clinical outcomes of bivalirudin for ischemic heart disease

Background-Current treatment strategies for percutaneous coronary revascula rization and acute coronary syndromes incorporate thrombin inhibition with either unfractionated or fractionated heparin. The peptide bivalirudin (Hir ulog) is a direct thrombin inhibitor whose pharmacological properties diffe r from those of heparin. We conducted a systematic overview (meta-analysis) to assess the effect of bivalirudin on 4 end points: death, myocardial inf arction, major hemorrhage, and the composite of death or infarction. Methods and Results-Six trials (5674 patients) represent the randomized, co ntrolled bivalirudin experience, including 4603 patients undergoing electiv e percutaneous coronary revascularization and 1071 patients with acute coro nary syndromes. ORs for the 4 clinical end points were calculated for each trial. Four trials (4973 patients) that compared bivalirudin with heparin w ere combined with the use of a random-effects model. In these trials, bival irudin was associated with a significant reduction in the composite of deat h or infarction (OR 0.73, 95% CI 0.57 to 0.95; P=0.02) at 30 to 50 days, or 14 fewer events per 1000 patients so treated. There also was a significant reduction in major hemorrhage for the same trials (OR 0.41, 95% CI 0.32 to 0.52; P<0.001, or 58 fewer events per 1000 patients so treated). A similar analysis combined 2 dose-ranging trials (701 patients) that compared thera peutic (activated partial thromboplastin time more than twice the control t ime) with subtherapeutic bivalirudin anticoagulation (activated partial thr omboplastin time less than twice the control time). Conclusions-Bivalirudin is at least as effective as heparin, with clearly s uperior safety. Thus, it provides an unprecedented net clinical benefit ove r heparin in patients with ischemic heart disease.