A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction - The PENTALYSE study

Background ORG31540/SR90107A, a synthetic pentasaccharide, is a selective i nhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibit ion with pentasaccharide may be an effective and safe antithrombotic co-the rapy in acute myocardial infarction. Methods and Results Patients (n = 333) with evolving ST-segment elevation a cute myocardial infarction were treated with aspirin and alteplase and rand omized to unfractionated heparin, given intravenously during 48 to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary a ngiography was performed at 90 min and on days 5 to 7. Thrombolysis in Myoc ardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the f our treatment groups. Among patients with TIMI 3 flow at 90 min and who did not undergo a coronary intervention (n = 155), a trend towards less reoccl usion of the infarct-related vessel on days 5 to 7 was observed with pentas accharide: 0.9% vs 7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during the 30-day follow-up period were performed in pat ients given pentasaccharide (39% vs 51% for unfractionated heparin; P=0.054 ). The primary safety end-point, the combined incidence of intracranial hae morrhage and need for blood transfusion, was identical with pentasaccharide and unfractionated heparin (7.1%). One non-fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide (0.4%). Conclusions In this study, pentasaccharide given together with alteplase wa s safe and as effective as unfractionated heparin in restoring coronary art ery patency. Prolonged administration of pentasaccharide was associated wit h a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patie nts presenting with ST-segment elevation acute myocardial infarction.