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


Eva Maria Becker, Forschungszentrum Aprath, Geb 500 R 509, Aprather Weg 18a, 42096 Wuppertal, Germany.
Tel.: +49 202 36 5433; fax: +49 202 36 8009.
E-mail: eva.becker1@bayer.com


Summary.  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: 1500 s−1). In-stent thrombus formation was analyzed under different treatments: vehicle (n = 7 animals); intravenous (i.v.) rivaroxaban (0.11, 0.33, and 1.0 μg kg–1 min−1) (n = 8); rivaroxaban + ASA (1.0 mg kg−1 i.v.) (n = 6); rivaroxaban + ASA (1.0 mg kg−1 i.v.) + clopidogrel (0.5 mg kg−1 i.v.) (n = 7); and ASA (1.0 mg kg−1 i.v.) + clopidogrel (0.5 mg kg−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.