Recent Advances in Antithrombin Therapy for Acute Coronary Syndromes

Abstract

CHEN AND LAU : Recent Advances in Antithrombin Therapy for Acute Coronary Syndromes. Unstable angina and acute myocardial infarction are leading causes of hospital admissions worldwide. Following the initiating event of atherosclerotic plaque rupture, activation of the coagulation cascade plays an important role in mediating local thrombosis. Novel antithrombotic agents have recently been developed and applied in clinical practice. The direct antithrombins have the advantage of inhibiting both fluid-phase and clot-bound thrombin. Despite a sound theoretical basis, the prototypical agent hirudin has been demonstrated to be only equivalent to unfractionated heparin as adjunctive therapy to thrombolysis in ST-elevation myocardial infarction. Although showing a better efficacy than unfractionated heparin in unstable angina/non-Q wave myocardial infarction, hirudin causes more major bleeding complications. Low-molecular-weight heparins have the advantages of a better bioavailability, longer half-life and dose-independent clearance, making subcutaneous administration possible and monitoring unnecessary. Enoxaparin has been proven to be superior to unfractionated heparin in two large randomised trials of unstable angina/non-Q wave myocardial infarction while equivalence is demonstrated for other low-molecular-weight heparins. A higher anti-Xa:anti-IIa ratio may explain the varying efficacy. In the near future low-molecular-weight heparins and newer antithrombin agents may replace unfractionated heparin in the management of acute coronary syndromes as ongoing clinical trials further define their roles. (J HK Coll Cardiol 1999;7:109-118)