Antithrombotic efficacy of a novel factor Xa inhibitor, FXV673, in a canine model of coronary artery thrombolysis

I We compared the antithrombotic efficacy of a potent factor Xa inhibitor, FXV673. to heparin and RPR109891, a GPIIb/IIIa antagonist, when used as adj unctive therapy in a canine model of rt-PA-induced coronary thrombolysis. 2 Thrombus formation was induced by electrolytic injury to stenosed coronar y artery, After thrombotic occlusion, a 135 min infusion of saline (n = 8), FXV673 (10, 30 or 100 mug kg(-1) + 1, 3, or 10 Mg kg(-1) min(-1), respecti vely; n=8 per dose), heparin (60 u kg (1) +0.7 u kg(-1) min(-1), n=8), or R PR109891 (30 mug kg(-1) + 0.45 mug kg(-1) min(-1), n=8), was initiated. Asp irin (5 mg kg(-1), i.v.) was administered to all animals. Fifteen minutes a fter the start of drug infusion, rt-PA was administered (100 mug kg(-1) + 2 0 mug kg(-1) min(-1) for 60 min). 3 The incidence of reperfusion in the high dose FXV673 (8/8, 100%) was sign ificantly greater than that in the heparin group (4/8, 50%), with a trend t o faster reperfusion (23 +/-5 min for FXV673 versus 41 +/- 11 min for hepar in). Only 2/8 (25%) of the vessels reoccluded in the high dose FXV673 group , compared to 4/4 (100%) and 5/5 (100%) vessels in the heparin and RPR10989 1 groups, respectively (P <0.05). 4 Throughout the protocol, blood flow was higher in the FXV673 treated grou p compared to other groups. FXV673 enhanced vessel patency in a dose-depend ent manner, 5 Compared to vehicle and heparin groups, the thrombus mass was decreased b y 60% in the high dose FXV673. FXV673, heparin and RPR109891 increased the bleeding time by 2.8, 1.7 and 4 fold, and APTT by 2.8, 2.7 and 1.2 fold, re spectively. 6 In conclusion, FXV673 is more effective than heparin and at least as effe ctive as RPR109891 when used as an adjunct during rt-PA-induced coronary th rombolysis.