Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as anantithrombotic agent a pilot study in the setting of coronary angioplasty

Aim of the study. To assess the antithrombotic properties of SR90107/ORG315 40, a sulfated pentasaccharide, which enhances specifically antithrombin In : mediated inactivation of factor-Xa, in a clinical setting known to promot e arterial thrombosis, i.e. coronary angioplasty. Methods and results. Percutaneous transluminal coronary angioplasty (PTCA) was carried our with conventional balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide, and 500 mg intravenous aspirin. Heparin was nor allowed before, during PTCA, and within 24 h after PTCA. The primar y end point was the rate of abrupt vessel closure during and within 24 h af ter the procedure. The sample size was set at 60 evaluable patients, in ord er to be able to conclude with a good level of confidence (>95%) that the a brupt vessel closure rate was less than 10%, ii less than 3 abrupt vessel c losures were observed. Seventy-one patients were included in the study, of whom 10 needed elective stenting, and were not considered as evaluable for efficacy. Two out of the 61 remaining evaluable patients experienced acute vessel closure during the study period [3.28%, 95% confidence interval (0.4 %; 11.4%)]. No major bleeding occurred. The drug plasma concentrations reac hed 1.91 +/- 0.39 mg/l, 10 min after pentasaccharide injection, and decreas ed on average to 1.18 +/- 0.27 mg/l at 2 h, and to 0.36 +/- 0.11 mg/l at 23 h after administration of pentasaccharide. Activated clotting time (ACT) a nd activated partial thromboplastin (aPTT) time remained within normal rang e. Thrombin-antithrombin complex levels fell from 22 +/- 17.1 to 4.5 +/- 3. 4 mu g/ml, prothrombin fragment 1+2 levels decreased from 2.15 +/- 1.01 to 1.73 +/- 0.87, and activated factor Vn levels decreased from 43.4 +/- 16.8 mU/ml to 18.9 +/- 7.3 mU/ml respectively from baseline to 2 h following inj ection of the tested drug. Conclusions. Administration of pentasaccharide led to the inhibition of thr ombin generation without modification of aPTT and ACT. The rate of abrupt v essel closure was within range of rates reported in historical series. Thus we conclude that the anti-thrombotic activity of pentasaccharide, as shown in this pilot trial in the setting of coronary angioplasty, deserves furth er investigation.