Bivalirudin.
Bivalirudin is a direct thrombin inhibitor (DTI) frequently used for anticoagulation in the setting of invasive cardiology, particularly percutaneous coronary intervention (PCI). Bivalirudin has a unique pharmacologic profile: unlike other marketed DTIs, it undergoes predominant non-organ elimination (proteolysis), and has the shortest half-life (approximately 25 min). Its affinity for thrombin is intermediate between that of lepirudin (highest) and argatroban (lowest)--this helps explain why it interferes with functional clotting assays to an extent intermediate between that achieved by these two other DTIs. This effect is best known for the PT (INR)--higher affinity for thrombin corresponds to lower molar DTI requirements to prolong the APTT; in turn, lower concentrations required for APTT prolongation (and, presumably, in-vivo effect) result in reduced PT (INR) prolongation. Bivalirudin is primarily used for its first FDA-approved indication, namely anticoagulation during percutaneous transluminal coronary angioplasty ("balloon angioplasty"), the most frequent type of PCI. Bivalirudin is also indicated for PCI with provisional use of glycoprotein IIb/IIIa antagonist therapy, and for patients with, or at risk of, heparin-induced thrombocytopenia (HIT), or HIT with thrombosis syndrome (HITTS), undergoing PCI. The bivalirudin development program has used a "quadruple" endpoint comprising a "triple" efficacy endpoint plus major bleeding - this approach anticipated the subsequent emphasis on strategies to improve clinical outcomes through bleeding reduction. Besides summarizing the key trials evaluating bivalirudin use for acute coronary syndrome (especially employing PCI), we review also the studies of bivalirudin as anticoagulant for "on-" and "off-pump" cardiac surgery, including both HIT and non-HIT situations.
Warkentin
Theodore E
TE
Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster Unniversity, Hamilton, Ontario, L8L 2X2 Canada. twarken@mcmaster.ca
Greinacher
Andreas
A
Koster
Andreas
A
D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D000595:Amino Acid Sequence; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006488:Hemostasis, Surgical / Q000379:methods; D006493:Heparin / Q000009:adverse effects; D006629:Hirudins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin