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Arterial antithrombotic and bleeding time effects of apixaban, a direct factor Xa inhibitor, in combination with antiplatelet therapy in rabbits
Author(s) -
WONG P. C.,
WATSON C. A.,
CRAIN E. J.
Publication year - 2008
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/j.1538-7836.2008.03092.x
Subject(s) - apixaban , antithrombotic , medicine , cardiology , bleeding time , anesthesia , pharmacology , rivaroxaban , platelet , warfarin , atrial fibrillation , platelet aggregation
Summary. Background : Optimal treatment of arterial thrombosis may include a combination of antiplatelet and anticoagulant drugs. We evaluated apixaban, a direct and highly selective factor Xa inhibitor, in combination with clinically relevant doses of aspirin and/or clopidogrel for prevention of arterial thrombosis in rabbits. Methods : Studies were conducted in rabbit models of electrically induced carotid artery thrombosis and cuticle bleeding time (BT). Apixaban 0.04 and 0.3 mg kg −1 h −1 or aspirin 1 mg kg −1 h −1 was infused intravenous (i.v.) continuously from 1 h before artery injury or cuticle bleed until the end of the experiment. Clopidogrel at 3 mg kg −1 was dosed orally once daily for three days, with the last dose given 2 h before injury. Results : Control thrombus weight and BT averaged 8.6 ± 0.9 mg and 181 ± 12 s, respectively ( n = 6 per group). Effective doses of apixaban that reduced thrombus weight by 20 and 50% (ED 20 and ED 50 ) were 0.04 and 0.3 mg kg −1 h −1 i.v., respectively. Addition of aspirin to apixaban ED 20 and ED 50 significantly reduced the thrombus weight from 7.4 ± 0.5 to 5.3 ± 0.3 and 3.6 ± 0.3 mg, respectively, with no significant increases in BT (190 ± 7 s vs.181 ± 9 and 225 ± 11 s, respectively). Addition of aspirin and apixaban (ED 20 dose) to clopidogrel produced a further significant reduction in thrombus weight from 5.3 ± 0.3 to 0.7 ± 0.1 mg. This combination of clopidogrel and aspirin with apixaban (ED 20 dose) produced a significant but moderate BT increase of 2.1 times control. Conclusions : The combination of apixaban and aspirin or apixaban, aspirin and clopidogrel can reduce formation of occlusive arterial thrombosis without excessive increases in BT in rabbits.