• Patrick A Lester, Dawn M Coleman, Jose A Diaz, Tatum O Jackson, Angela E Hawley, Angela R Mathues, Brandon T Grant, Robert M Knabb, Eduardo Ramacciotti, Charles E Frost, Yan Song, Thomas W Wakefield, and Daniel D Myers.
• From the Unit for Laboratory Animal Medicine (P.A.L., D.D.M.) and Conrad Jobst Vascular Research Laboratories (P.A.L., D.M.C., J.A.D., T.O.J., A.E.H., A.R.M., B.T.G., T.W.W., D.D.M.), University of Michigan, Ann Arbor; and Global Clinical Research, Research & Development (R.M.K., E.R.) and Exploratory Clinical and Translational Research (C.E.F., Y.S.), Bristol-Myers Squibb Company, Princeton, NJ.
• Arterioscler. Thromb. Vasc. Biol. 2017 May 1; 37 (5): 942-948.

ObjectiveWarfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy.Approach And ResultsA well-documented heterotopic aortic valve porcine model was used to test the hypothesis that apixaban has comparable efficacy to warfarin for thromboprophylaxis of mechanical heart valves. Sixteen swine were implanted with a bileaflet mechanical aortic valve that bypassed the ligated descending thoracic aorta. Animals were randomized to 4 groups: control (no anticoagulation; n=4), apixaban oral 1 mg/kg twice a day (n=5), warfarin oral 0.04 to 0.08 mg/kg daily (international normalized ratio 2-3; n=3), and apixaban infusion (n=4). Postmortem valve thrombus was measured 30 days post-surgery for control-oral groups and 14 days post-surgery for the apixaban infusion group. Control thrombus weight (mean) was significantly different (1422.9 mg) compared with apixaban oral (357.5 mg), warfarin (247.1 mg), and apixiban 14-day infusion (61.1 mg; P<0.05).ConclusionsApixaban is a promising candidate and may be a useful alternative to warfarin for thromboprophylaxis of mechanical heart valves. Unlike warfarin, no adverse bleeding events were observed in any apixaban groups.© 2017 American Heart Association, Inc.

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