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.