Thrombin antagonists and antiplatelet agents.
The clinical benefits of thrombolytic therapy for the treatment of myocardial infarction are recognized widely. However, 2 major limiting factors have become evident: (1) 20-25% of coronary arterial thrombi are resistant to lysis; and (2) coronary reocclusion occurs in 10-15% of patients. There is increasing evidence that both phenomena are caused by heightened procoagulant activity localized primarily at the site of atheromatous plaque rupture. Thrombin, the pivotal enzyme in all coagulation processes, is activated, stimulating fibrin formation and platelet aggregation. Platelet activation, by thrombin- and nonthrombin-mediated mechanisms, occurs as well, further increasing thrombotic tendency. Thus, a potent and well-localized procoagulant state may be continuously amplified, increasing both during and frequently after thrombolytic therapy. Current treatment strategies are designed to enhance fibrinolytic and anticoagulant activity, while neutralizing the expression of procoagulant factors. Thrombin antagonism and platelet inhibition, primarily with heparin and aspirin, respectively, form the mainstay of conjunctive therapy. Their benefits have been recognized, decreasing thromboembolic events and patient mortality. However, intrinsic limitations suggest that more potent and selective agents will be required to overcome effectively the problems of thrombolytic resistance and coronary reocclusion. In experimental models, specific thrombin antagonists and antiplatelet agents have shown superiority over heparin and aspirin. Further investigation to define the overall safety and efficacy profile of these newer agents will be required, however, prior to their widescale implementation in clinical practice.
Becker
R C
RC
Division of Cardiology, University of Massachusetts Medical School, Worcester 01655.
D000991:Antithrombins / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors