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Effects of rivaroxaban, acetylsalicylic acid and clopidogrel as monotherapy and in combination in a porcine model of stent thrombosis
Author(s) -
BECKER E.M.,
PERZBORN E.,
KLIPP A.,
LÜCKER C.,
BÜTEHORN U.,
KAST R.,
BADIMON J. J.,
LAUX V.
Publication year - 2012
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12033
Subject(s) - rivaroxaban , medicine , clopidogrel , thrombus , antithrombotic , thrombosis , stent , aspirin , pharmacology , anesthesia , cardiology , warfarin , atrial fibrillation
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.