Cardiomyopathies are a major cause of morbidity and death in domestic cats. In a large postmortem study,1 8.5% of cats had evidence of acquired myocardial disease. Arterial thromboembolism is a common complication of cardiomyopathy in cats, which causes death and profound morbidity. Previous studies1,2 have found that cardiac-origin thromboembolism may be a complication in 15% to 48% of cats with hypertrophic cardiomyopathy. Approximately 90% of cardiac thromboembolic events in cats are thromboemboli in the distal part of the aorta that bilaterally occlude the femoral and iliac arteries. A retrospective study3 of 100 cats with distal aortic thromboembolism found that the rate of survival past the initial episode of thromboembolism was only 37%.
Medications used to prevent arterial thromboembolism in cats with heart disease include several antiplatelet and anticoagulant drugs. Although antiplatelet medications such as clopidogrel and aspirin are often administered to prevent cardiac thromboembolism in cats, recurrence rates remain high.3,4,a Targeted warfarin administration has been used to treat and prevent thromboembolism in cats,3,5 but data regarding safety and efficacy are lacking. High variability in the definition of a safe and effective dose among individual cats and over time as well as the need for frequent coagulation testing to ensure appropriate administration make warfarin treatment risky and impractical in cats. Low-molecular-weight heparins may be effective for the prevention and treatment of thromboembolic disease in cats, but low-molecular-weight heparins must be administered by injection, which some owners may be unwilling to do, and current costs are prohibitive for long-term use in many situations.
Apixaban is a novel, orally administered factor Xa inhibitor approved by the US FDA in 2012 to reduce the risk of stroke or systemic embolism in human patients with nonvalvular atrial fibrillation. Apixaban is not approved for use in nonhuman species. Clinical trials of apixaban in humans with nonvalvular atrial fibrillation have revealed that the drug is superior to warfarin treatment for reducing the risk of stroke or systemic embolism.6 Apixaban treatment in humans can be safely used by means of standardized administration with no need for continuous monitoring of coagulation.7 Therefore, apixaban holds great potential for replacing targeted warfarin treatment as the standard of care for a variety of thrombotic conditions in humans.
In humans with chronic atrial fibrillation, stasis of blood flow within the left atrium is thought to be the primary mechanism responsible for thrombus formation.8,9 In human medicine, anticoagulation is preferred over antiplatelet treatment when stasis of blood flow is the primary thrombotic mechanism, as for deep vein thrombosis and atrial fibrillation.10–12 Stasis of flow within the left atrium is also proposed to be a primary mechanism of thrombus formation in cats with cardiomyopathy. Thus, it is not surprising that antiplatelet strategies have often been unsatisfying for preventing thromboembolic complications in cats with cardiomyopathy. In cats with heart disease, anticoagulant treatment is more likely than antiplatelet treatment to prevent intra-atrial thrombus formation and promote resolution of existing thrombi through endogenous fibrinolysis.
A critical need exists to identify an effective, safe, and cost-effective anticoagulant that can both prevent thrombus formation and treat existing thrombi in cats with cardiomyopathy. On the basis of existing data from human studies showing excellent efficacy of apixaban in patients with thromboembolism and deep vein thrombosis,6,13–15 apixaban would appear to be a strong candidate to fulfill this need. Apixaban pharmacokinetics, pharmacodynamics, and metabolism have been studied in multiple species7,16–19 but to our knowledge have not been evaluated in cats. The objective of the study reported here was to determine the pharmacokinetic and pharmacodynamic properties of apixaban after administration to healthy cats.
Supported by the Veterinary Pharmacology Research Foundation and by an American College of Veterinary Internal Medicine Cardiology Resident Grant.
The authors have no conflicts of interest.
Results of this study were presented in abstract form at the American College of Veterinary Internal Medicine Forum, Nashville, Tenn, June 2014.
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Eliquis, provided by Bristol-Myers Squibb, New York, NY.
C18 reverse-phase liquid chromatography column, Waters Corp, Milford, Mass.
C18 filter frit guard column, Phenomenex, Torrance, Calif.
DiaPharma factor × kit, DiaPharma Group Inc, West Chester, Ohio.
LAtrol abnormal control, American Diagnostica Inc, Stanford, Conn.
Multiskan spectrum, Thermo Scientific, Waltham, Mass.
WinNonlin software, Pharsight Corp, Mountain View, Calif.
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