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The benefit‐to‐risk profile of melagatran is superior to that of hirudin in a rabbit arterial thrombosis prevention and bleeding model
Author(s) -
Klement P.,
Carlsson S.,
Rak J.,
Liao P.,
Vlasin M.,
Stafford A.,
Johnston M.,
Weitz J. I.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00060.x
Subject(s) - hirudin , medicine , direct thrombin inhibitor , thrombosis , discovery and development of direct thrombin inhibitors , thrombin , anesthesia , blood flow , unstable angina , pharmacology , surgery , platelet , cardiology , myocardial infarction , dabigatran , atrial fibrillation , warfarin
Summary. Although hirudin is better than heparin at preventing recurrent ischemia in patients with unstable angina, hirudin produces more bleeding. The purpose of this study was to use a rabbit arterial thrombosis prevention and ear bleeding model to determine whether for equivalent efficacy, melagatran, a synthetic direct thrombin inhibitor, is safer than hirudin. A combination of balloon injury and stasis was used to induce thrombosis in the distal aorta, and patency and blood flow were continuously monitored with ultrasonic flow probes. Rabbits were randomized to melagatran (in total doses of 78–313 nmol kg −1 ), hirudin (in total doses of 18–107 nmol kg −1 ), or saline over 90 min. To assess safety, blood loss from standardized ear incisions was measured. Both melagatran and hirudin produced dose‐dependent increases in patency and blood flow. At doses that maintained the highest levels of patency, however, melagatran produced 2–3‐fold less bleeding than hirudin. Thus, at maximally effective doses, melagatran causes less bleeding than hirudin in this model. These findings raise the possibility that some direct thrombin inhibitors are safer than others.