Bivalirudin: pharmacology and clinical applications.
Bivalirudin (Hirulog, Angiomax) is a specific, reversible and direct thrombin inhibitor with a predictable anticoagulant effect. It is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration. Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly by binding to thrombin catalytic site and anion-binding exosite I in a concentration-dependent manner. Bivalirudin prolongs activated partial thromboplastin time, prothrombin time, thrombin time and activated clotting time (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy. Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective contemporary percutaneous coronary intervention (PCI). In respect to combined ischemic and hemorrhagic endpoints of death, myocardial infarction, unplanned urgent revascularization and major bleeding during PCI (including subgroups of patients with renal impairment and diabetes) bivalirudin is not inferior to unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin has been consistently shown to have significantly less in-hospital major bleeding than heparin alone or heparin in combination with a GpIIb/IIIa inhibitor. Bivalirudin appears to be also safe and effective during PCI in patients with heparin-induced thrombocytopenia. Finally, data from PCI studies support the safety and efficacy of bivalirudin, although its direct randomized comparison with unfractionated heparin is lacking.
Shammas
Nicolas W
NW
Midwest Cardiovascular Research Foundation, Cardiovascular Medicine, PC, 1236 E. Rusholme, Suite 300, Davenport, IA 52803, USA. shammas@mchsi.com
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity*; D002315:Cardiopulmonary Bypass; D003327:Coronary Disease / Q000188:drug therapy; D003362:Cost-Benefit Analysis; D006629:Hirudins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity*; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D013917:Thrombin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013917:Thrombin; C074619:bivalirudin