Clinical Outcomes of Bivalirudin for Ischemic Heart Disease

Abstract

Background-Current treatment strategies for percutaneous coronary revascularization and acute coronary syndromes incorporate thrombin inhibition with either unfractionated or fractionated heparin. The peptide bivalirudin (Hirulog) is a direct thrombin inhibitor whose pharmacological properties differ from those of heparin. We conducted a systematic overview (meta-analysis) to assess the effect of bivalirudin on 4 end points: death, myocardial infarction, major hemorrhage, and the composite of death or infarction. Methods and Results-Six trials (5674 patients) represent the randomized, controlled bivalirudin experience, including 4603 patients undergoing elective percutaneous coronary revascularization and 1071 patients with acute coronary syndromes. ORs for the 4 clinical end points were calculated for each trial. Four trials (4973 patients) that compared bivalirudin with heparin were combined with the use of a random-effects model. In these trials, bivalirudin was associated with a significant reduction in the composite of death or infarction (OR 0.73, 95% CI 0.57 to 0.95; Pϭ0.02) 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; PϽ0.001, or 58 fewer events per 1000 patients so treated). A similar analysis combined 2 dose-ranging trials (701 patients) that compared therapeutic (activated partial thromboplastin time more than twice the control time) with subtherapeutic bivalirudin anticoagulation (activated partial thromboplastin time less than twice the control time). Conclusions-Bivalirudin is at least as effective as heparin, with clearly superior safety. Thus, it provides an unprecedented net clinical benefit over heparin in patients with ischemic heart disease. (Circulation. 1999;100:2049-2053.)

Direct Thrombin Inhibitors in Acute Coronary Syndromes

“…Although a meta-analysis suggests that bivalirudin is safer than heparin for all clinical indications in which the 2 agents were compared, 47 recent data from the Hirulog Early Reperfusion Occlusion (HERO)-2 trial indicate that bivalirudin produces more bleeding than heparin when used in conjunction with streptokinase. Post hoc analysis suggests that the excess bleeding can be explained by the fact that bivalirudin produced a higher APTT than heparin.…”

Emerging Anticoagulant Drugs

“…103 As in the original report, the reanalysis demonstrated lower rates of major bleeding with bivalirudin than with heparin (3.5% and 9.3%, respectively; PϽ0.001). 103,104 Recent meta-analyses 86,105 have confirmed that bivalirudin seems to be an effective alternative to heparin in patients undergoing coronary angioplasty. More contemporary studies have evaluated the utility of bivalirudin in patients undergoing coronary stenting.…”

“…Rates of major bleeding were significantly lower in patients given bivalirudin than in those treated with heparin. Therefore, based on available data, including recent meta-analyses, 86,105 bivalirudin seems to be at least as effective as heparin in patients undergoing percutaneous coronary interventions. In this setting, bivalirudin produces less bleeding and seems to obviate the need for adjunctive GPIIb/IIIa antagonists in most patients.…”

The status of new anticoagulants

“…Hirudin (Potzch et al, 1994;Reiss et al, 1995;Greinacher et al, 1999a,b;Farner et al, 2001;Lewis et al, 2001) and argatroban (Lewis et al, 2001(Lewis et al, , 2003 are approved for the treatment of heparininduced thrombocytopenia, whereas bivalirudin is licensed as an alternative to heparin in patients undergoing percutaneous coronary indications (Bittl, 1995;Bittl et al, 1995Bittl et al, , 2001Kong et al, 1999;Lincoff et al, 2002Lincoff et al, , 2003Weitz & Buller, 2002). Of the newer agents, ximelagatran, a prodrug of melagatran, is the first orally available direct thrombin inhibitor and has undergone phase III clinical evaluation for the prevention and treatment of venous thromboembolism and for the prevention of cardioembolic events in patients with atrial fibrillation.…”