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

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....

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Published in:Journal of thrombosis and haemostasis 2012-12, Vol.10 (12), p.2470-2480
Main Authors: BECKER, E.M., PERZBORN, E., KLIPP, A., LÜCKER, C., BÜTEHORN, U., KAST, R., BADIMON, J. J., LAUX, V.
Format: Article
Language:English
Subjects:
Acute coronary syndromes
Angina pectoris
Animals
aspirin
Aspirin - administration & dosage
Aspirin - therapeutic use
Blood clots
clopidogrel
Drug Therapy, Combination
Female
Morpholines - administration & dosage
Morpholines - therapeutic use
Platelet Aggregation
Rivaroxaban
stent thrombosis
Stents
Stents - adverse effects
Swine
Swine, Miniature
Thiophenes - administration & dosage
Thiophenes - therapeutic use
Thrombosis - drug therapy
Thrombosis - etiology
Ticlopidine - administration & dosage
Ticlopidine - analogs & derivatives
Ticlopidine - therapeutic use
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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 
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.12033