Dual therapy with clopidogrel and rivaroxaban in cats with thromboembolic disease

Abstract

Objectives Feline arterial thromboembolism (ATE), an often devastating outcome, was recently shown to affect 11.3% of cats with hypertrophic cardiomyopathy over 10 years. Current American College of Veterinary Internal Medicine guidelines recommend the use of clopidogrel in cats at risk for ATE, with addition of a factor Xa inhibitor in very high risk or post-ATE cases. To date, no studies have examined the safety or efficacy of this combined antithrombotic therapy. This retrospective case series aimed to assess the frequency and type of adverse events that occurred in cats prescribed dual clopidogrel and rivaroxaban therapy. Secondary aims were to evaluate indications for dual therapy and clinical outcome. Methods The study included 32 cats prescribed clopidogrel (18.75 mg PO q24h) and rivaroxaban (2.5 mg PO q24h) on an outpatient basis over a 5-year period. Results Cats were prescribed dual therapy for at least one of the following: ATE event (n = 18), presence of an intracardiac thrombi (n = 17) or presence of spontaneous echocardiographic contrast (SEC) (n = 16). Five cats experienced adverse effects that could be attributed to medications, a median of 13 days from initiation (epistaxis, hematemesis, hematochezia or hematuria). No cat required hospitalization as a result of these events. Median survival time from onset of therapy was 257 days (interquartile range [IQR] = 38–497) for all cats, 502 days (IQR = 171–663) for ATE cats, 725 days (IQR = 133–856) for cats with an ATE to two or more limbs and 301 days (IQR = 221–431) for cats with only one limb affected. Recurrence rate of ATE while on dual therapy was 16.7%; no cat newly developed an ATE while on dual therapy. Conclusions and relevance Dual antithrombotic therapy with clopidogrel and rivaroxaban resulted in a low reported incidence of adverse events. Cats placed on dual therapy for an ATE event experienced a low rate of recurrence and effective thromboprophylaxis was achieved in cats with intracardiac thrombi or SEC.

The Feline Cardiomyopathies: 2. Hypertrophic cardiomyopathy

“…A recent study retrospectively examined use of clopidogrel in combination with rivaroxaban in cats with ATE, in cats with intracardiac thrombi and in cats with spontaneous echocardiographic contrast. 171 Side effects (epistaxis, hematemesis, hematochezia or hematuria) occurred in 5/32 cats but none required hospitalization. it should also be noted that clopidogrel is bitter.…”

“…Clopidogrel, either alone or possibly in combination with rivaroxaban, is currently the only drug that has been shown to decrease the incidence of recurrent systemic ATE in a population of cats. 170,171 While clopidogrel has only been shown to prevent ATE recurrence, one can probably assume that if a drug can delay or reduce the risk of ATE in a population of cats that has already experienced one bout of ATE, it can probably delay or reduce the risk of the first formation of a left auricular thrombus also. However, it is not 100% efficacious due to factors such as differences in bioavailability from cat to cat, polymorphisms in genes that encode for platelet proteins, and owner adherence/compliance.…”

“…These anticoagulants include the low molecular weight heparins (eg, enoxaparin [0.75-1 mg/kg SC q6-12h]) and the selective Xa inhibitors (eg, rivaroxaban [0.5-1 mg/kg Po q24h]; apixaban [0.625 mg/cat Po q12h]). 171,[174][175][176][177][178] Potential adverse effects primarily relate to bleeding complications. A recent study retrospectively examined use of clopidogrel in combination with rivaroxaban in cats with ATE, in cats with intracardiac thrombi and in cats with spontaneous echocardiographic contrast.…”

The Feline Cardiomyopathies: 1. General concepts

“…110 Another approach is to administer clopidogrel (antiplatelet) and rivaroxaban (anticoagulant; 0.5-1 mg/kg Po q24h) together. 111 The primary problem with this approach is the high cost of rivaroxaban.…”

Retrospective Evaluation of Intravenous Enoxaparin Administration in Feline Arterial Thromboembolism

“…The induction of a hypocoagulable state is imperative in treating FATE [ 17 ]. This state is achieved with the use of unfractionated heparin (UFH) [ 1 , 2 , 7 , 8 , 10 , 14 ], low molecular weight heparins (LMWHs) [ 8 , 9 , 10 , 18 ], or oral factor-Xa inhibitors [ 19 ] with or without platelet function inhibitors (acetyl salicylic acid, clopidrogrel, abciximab). In 2 large studies regarding mixed medical treatment, including UFH in all [ 2 ] or most [ 7 ] of the cats, an overall survival rate of 37% [ 2 ] and 42% [ 7 ], respectively, with relatively low risk of hemorrhage was achieved.…”