Bivalirudin: a direct thrombin inhibitor
Pharmacology review published in Clin Ther (2002)
Abstract
BACKGROUND: Studies of the anticoagulant effects of hirudin, which is derived from the saliva of the leech Hirudo medicinalis, led to the development of compounds that can directly inhibit thrombin activity without the need for additional cofactors. One of these is the direct thrombin inhibitor bivalirudin, which has recently been approved by the US Food and Drug Administration for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. OBJECTIVE: This is a review of the pharmacologic properties, efficacy, tolerability, and potential cost-effectiveness of bivalirudin in the treatment of ischemic coronary syndromes. METHODS: Articles were identified by searches of MEDLINE (1966-September 2001), International Pharmaceutical Abstracts (1970-September 2001), and the Iowa Drug Information Service (1966-September 2001) using the terms bivalirudin and Hirulog. The reference lists of retrieved articles were also reviewed for relevant articles. RESULTS: Bivalirudin is a synthetic polypeptide that directly inhibits thrombin by binding simultaneously to its active catalytic site and its substrate recognition site. After intravenous administration, peak plasma concentrations occur in 2 minutes. In patients given a 1.0-mg/kg bolus followed by a 2.5-mg/kg per hour infusion, a median activated clotting time of 346 seconds is achieved with little interpatient or intrapatient variability. Clearance of bivalirudin occurs through a combination of renal elimination and proteolytic cleavage, and doses may need to be decreased in the presence of renal dysfunction. In patients undergoing percutaneous coronary interventions, bivalirudin has been associated with equivalent efficacy but lower bleeding rates (P < 0.001) than unfractionated heparin (UFH). Data from the Hirulog Early Reperfusion/Occlusion-2 study suggest no reduction in mortality with bivalirudin compared with heparin when either is added to aspirin and streptokinase in patients with acute myocardial infarction, despite a lower reinfarction rate (P < 0.001). Experience with bivalirudin in patients with unstable angina and heparin-induced thrombocytopenia (HIT), as well as in patients receiving glycoprotein IIb/IIIla inhibitors, is limited. The differences in bleeding rates between bivalirudin and heparin in published clinical trials probably reflect differences in levels of anticoagulation achieved in comparator groups. CONCLUSIONS: Given its high cost, bivalirudin should be reserved for use as an alternative to UFH, primarily in patients with HIT, until clinical trials have more clearly demonstrated its benefits in terms of efficacy or safety.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Comprehensive pharmacologic review: bivalirudin (a synthetic polypeptide directly inhibiting thrombin via simultaneous catalytic-site and substrate-recognition-site binding) is cleared by combined renal elimination and proteolytic cleavage, with reduced bleeding rates vs. heparin in PCI.
Por qué esto importa para la hirudoterapia
Esta revisión examinó las propiedades farmacológicas, la eficacia, la tolerabilidad y la relación coste-efectividad de la bivalirudina —un inhibidor directo de la trombina polipeptídico sintético desarrollado a partir de estudios de la hirudina derivada de la saliva de Hirudo medicinalis— en síndromes coronarios isquémicos. Es relevante para el ámbito de ASH como un ejemplo concreto de cómo una molécula del secretoma de la sanguijuela inspiró un anticoagulante aprobado por la FDA para angina inestable sometida a angioplastia coronaria, con tasas de sangrado reportadas menores que las de la heparina no fraccionada (P < 0,001). El resumen aporta datos farmacocinéticos detallados (pico plasmático en 2 minutos, ACT mediana de 346 segundos) y señala la necesidad de ajuste de dosis en la disfunción renal. Sin embargo, se trata de una revisión farmacológica centrada en un derivado sintético, no en la hirudoterapia ni en la aplicación de sanguijuelas vivas; el resumen concluye que, debido a su alto coste, la bivalirudina debe reservarse principalmente para pacientes con trombocitopenia inducida por heparina hasta que nuevos ensayos aclaren sus beneficios.
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Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: 18 de junio de 2026