Effects of rivaroxaban, acetylsalicylic acid and clopidogrel as monotherapy and in combination in a porcine model of stent thrombosis

Abstract

Background: Despite standard dual antiplatelet therapy (DAT) (acetylsalicylic acid [ASA] and clopidogrel), there is a ≥1.4% incidence of in-stent thrombosis in patients with acute coronary syndrome. Factor Xa inhibitors are being investigated for secondary prevention after acute coronary syndrome. Objective:To study the antithrombotic effects of the FXa inhibitor rivaroxaban alone or in combination with DAT. Methods: Bare metal stents (12 per animal, three per intervention period) were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood (shear rate: 1500s-1). In-stent thrombus formation was analyzed under different treatments: vehicle (n=7 animals); intravenous (i.v.) rivaroxaban (0.11, 0.33, and 1.0μgkg-1min-1) (n=8); rivaroxaban+ASA (1.0mg kg-1 i.v.) (n=6); rivaroxaban+ASA (1.0mgkg-1 i.v.) +clopidogrel (0.5mgkg-1 i.v.) (n=7); and ASA (1.0mgkg-1 i.v.)+clopidogrel (0.5mgkg-1 i.v.) (n = 6). Results: Rivaroxaban dose-dependently reduced stent thrombus weight by ≤66% vs. vehicle (P<0.05, all doses). Rivaroxaban+ASA further reduced thrombus weight vs. vehicle (86% at the highest rivaroxaban dose; P<0.001). DAT reduced thrombus weight by ≤79%. However, rivaroxaban+ASA+clopidogrel almost completely abolished in-stent thrombus formation (98% reduction vs. vehicle at the highest rivaroxaban dose; P<0.001). Conclusions: Our data on the inhibitory effect of rivaroxaban alone or with DAT are consistent with the ATLAS 2 trial findings, and support its potential use for preventing stent thrombosis after stent deployment. © 2012 International Society on Thrombosis and Haemostasis.