Direct thrombin inhibitors as adjuncts to thrombolytic therapy.

Thrombolytic therapy aims to achieve rapid and sustained infarct-related artery patency, although this results in a procoagulant state. Heparin has limitations as an antithrombin agent, which has led to clinical investigation of alternative agents. Direct thrombin inhibitors, as adjuncts to thrombolytic therapy, have been shown to increase 90 minute Thrombolysis in Myocardial Infarction (TIMI)-3 flow rates and reduce reinfarction, when compared with heparin. These results have been achieved with an acceptable risk of bleeding, when administered in appropriate dosing regimens. When the direct thrombin inhibitor hirudin was administered at a mean of 34 and 50 minutes after thrombolytic therapy in large clinical trials, there was no reduction in mortality. In contrast, in several angiographic studies, direct thrombin inhibitors were administered prior to thrombolysis. The effect on mortality of the administration of hirulog prior to streptokinase is currently being examined.