Efegatran sulfate as an adjunct to streptokinase versus heparin as an adjunct to tissue plasminogen activator in patients with acute myocardial infarction

Background Previous clinical studies have shown that direct antithrombins c an accelerate clot lysis after treatment with streptokinase in acute myocar dial infarction (MI). Efegatran is a new direct antithrombin, which in expe rimental animals has been shown to enhance thrombolysis, reduce rare of reo cclusion, and limit infarct size. This study was designed to compare the ef ficacy of efegatran plus streptokinase versus heparin plus accelerated tiss ue plasminogen activator (TPA) in coronary reperfusion in acute MI. Methods and Results In this randomized, dose-finding study (n = 245), we in itially explored 4 doses of efegatran sulfate in combination with streptoki nase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared wi th heparin plus accelerated TPA. The primary end point was complete potency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct- related vessel potency (TIMI grade 2 or 3) and complete potency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53 % in the heparin/TPA group (P = not significant). In-hospital mortality rat e was 5% for the efegatron/streptokinase group versus 0% for the heparin/TP A group (P = not significant). Major breeding occurred in 23% of patients i n the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred. Conclusions The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early p atency. In addition, there is no indication that this experimental treatmen t can achieve better clinical outcome.