Newer antithrombin agents in acute coronary syndromes

Thrombin, through its procoagulant and prothrombotic actions, plays a central role in the pathogenesis of unstable angina and acute myocardial infarction. Antithrombin therapy with unfractionated heparin has several important disadvantages, such as a variable anticoagulant effect, sensitivity to platelet factor 4, an inability to inhibit clot-bound thrombin, and the potential to cause thrombocytopenia. Alternative approaches have focused on novel anticoagulants, including direct antithrombins (eg, hirudin) and low-molecular-weight heparins (eg, enoxaparin). Direct antithrombins bind tightly to thrombin without requiring the cofactor antithrombin. Low-molecular-weight heparins display enriched anti-factor Xa activity, improved bioavailability, and facilitated administration versus unfractionated heparin. Recent trials demonstrate that direct antithrombins reduce rates of death and myocardial infarction early in patients without ST elevation, but the treatment effect diminishes over time. In contrast, treatment with enoxaparin shows superiority versus unfractionated heparin, and the treatment effect is durable over time. Whether thrombolysis with adjunctive treatment with low-molecular-weight heparins will show efficacy in patients with ST-segment elevation is the subject of ongoing trials. (Am Heart J 1999;138:S563-S569.)