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.


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.
Cardiovascular Research, Bayer Pharma AG, Wuppertal, Germany. eva.becker1@bayer.com
E M
EM
Becker
E
E
Perzborn
A
A
Klipp
C
C
Lücker
U
U
Bütehorn
R
R
Kast
J J
JJ
Badimon
V
V
Laux
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D010974:Platelet Aggregation; D000069552:Rivaroxaban; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D013556:Swine, Miniature; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin