A new protocol for feline arterial thromboembolism prophylaxis: rivaroxaban + clopidogrel
The FAT CAT study of 2015:
Hogan DF, Fox PR, Jacob K, et al.
Secondary prevention of cardiogenic arterial thromboembolism in the cat: the double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs aspirin trial (FAT CAT).
J Vet Cardiol 2015; 17: S306–S317
https://pubmed.ncbi.nlm.nih.gov/26776588/
…demonstrated superiority of clopidogrel over aspirin in cats with a history of cardiogenic arterial thromboembolism (CATE). However, even clopidogrel left plenty of room for improvement as well over half of the cats did suffer further thromboembolic events despite treatment. Furthermore, we know that there is considerable variability between individual cats in their responses to clopidogrel:
Li RHL, Stern JA, Ho V, et al.
Platelet activation and clopidogrel effects on ADP-induced platelet activation in cats with or without the A31P mutation in MYBPC3.
J Vet Intern Med 2016; 30: 1619–1629
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032873/
Thus, the search for better regimens has continued. Rivaroxaban, an oral factor Xa inhibitor anticoagulant, has been the coming thing for the last year or two now and recently, preliminary evidence has been reaching publication:
J Feline Med Surg. 2022 Apr; 24(4): 277–283.
Dual therapy with clopidogrel and rivaroxaban in cats with thromboembolic disease
Sara T Lo, Ashley L Walker,1 Catherine J Georges,1 Ronald HL Li, and Joshua A Stern
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830184/
Although this study includes only 32 cats, there are some pretty noteworthy findings.
‘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.’
Well, to be honest, I take that as somewhat positive that, clearly, there was a significant inhibition of platelet function. Given that CATE is a highly fatal condition with severe welfare impact, a certain incidence of adverse effects is probably tolerable.
Secondly:
‘Of the cats that were initially prescribed combined clopidogrel and rivaroxaban due to an ATE event, [only] 3/18 (16.7%) had recurrent ATE events while on dual therapy‘
…and thirdly:
‘None of the cats that were prescribed clopidogrel and rivaroxaban for spontaneous echocontrast or intracardiac thrombi (n = 14) experienced ATE‘
That’s good enough for me -as an interim protocol, pending further data. It’s never a nice feeling to scan a cat’s heart and see a big thrombus flapping around in the left atrium. To know that there’s a good chance of averting disaster with combination therapy is great.
The unanswered issue here is what to do about cats with enlarged left atrium minus spontaneous echocontrast/thrombus/previous CATE. Or, to be more specific, how big does a left atrium have to be to justify dual therapy? In cats with only marginally dilated LA the risk:benefit ratio does become more of a consideration. Ultimately, we don’t know the answer to this yet. I don’t think I shall be putting cats with an 18mm left atrium (long axis, max end-systolic diameter) on both. 24mm maybe.
Doses: cats were prescribed clopidogrel (18.75 mg PO q24h) and rivaroxaban (2.5 mg PO q24h)
Both drugs, obviously, are unlicensed in cats.
