A systematic review on the role of bivalirudin in patients undergoing percutaneous coronary interventions: primus inter pares or a falling star?

Abstract

Intracoronary thrombosis triggered by ruptured or eroded atherosclerotic plaques constitutes the predominant underlying cause of acute coronary syndromes (ACS). Thrombin is considered a central enzyme in hemostasis and thrombosis, and a well-established target for anticoagulant therapies. Bivalirudin was introduced in the clinical practice as a promising, reversible, direct thrombin inhibitor with a predictable anticoagulant effect. Initial randomized clinical trials demonstrated that bivalirudin compared with heparin on top of a glycoprotein IIb/IIIa inhibitor was associated with a significant reduction of major bleeding and favorable net clinical outcomes in patients undergoing percutaneous coronary interventions (PCI). The HORIZON-AMI trial even indicated mortality benefit in bivalirudin-treated patients. Thereby, the 2011 and 2012 European Society of Cardiology Guidelines on the management of non-ST-segment elevation ACS and ST-segment elevation myocardial infarction positioned bivalirudin as the anticoagulant of choice in the PCI setting. Further randomized studies, better reflecting routine clinical practice, revealed significantly increased rates of stent thrombosis and myocardial infarction in the bivalirudin arm. Additionally, these findings were corroborated in the subsequent meta-analyses. Speculations that excessive occurrence of stent thrombosis and myocardial infarction may be caused by too short duration of post PCI bivalirudin infusion did not find confirmation in the latest MATRIX trial. In this systematic review, we aim to assess the efficacy and safety of bivalirudin therapy in patients undergoing PCI and to formulate recommendations on the bivalirudin use for clinicians. In our opinion, the research evidence and pharmacoeconomic considerations strongly support the use of bivalirudin in PCI patients at high risk of bleeding complications, while in other situations old and inexpensive UFH or enoxaparin remain the first line antithrombotic drugs.