Meet The Author
November 2025
Ben Brainard VMD, DACVAA, DACVECC
I am currently a professor at the University of Georgia College of Veterinary Medicine in Athens, GA.
Therapy with clopidogrel or rivaroxaban has equivalent impacts on recurrence of thromboembolism and survival in cats following cardiogenic thromboembolism: the SUPERCAT study
Brainard BM, Coleman AE, Kurosawa A, Rush JE, Hogan DF, Brooks MB, Kraus MS
The Study Background
I have long been interested in the mechanics of clot formation and also the impact of anticoagulant medications on clot formation in veterinary species. A recurring question regarding cats with cardiogenic arterial thromboembolic disease what the primary mechanism is for clot formation. Is it abnormal blood flow through the diseased heart resulting in platelet activation (e.g. due to increased shear stress) or is it due to coagulation factor activation (e.g. due to areas of low blood flow, similar to deep venous thrombosis in humans). Could it be a combination of both? Even though the incidence of arterial thromboembolism in cats is relatively low, the clinical consequences are devastating and thus I felt that this was a very important topic to focus on.
What is the primary knowledge gap your study aims to address?
We wanted to compare survival and time to recurrence of cardiogenic arterial thromboembolic disease (ATE) in cats that received either clopidogrel or rivaroxaban as single agent anticoagulants.
The Study Design
This was a prospective, double-masked, randomized, multicenter clinical trial, carried out at 18 veterinary specialty hospitals in the US and the UK. Because it is difficult to identify cats that will develop thromboembolism prior to the event, we chose to study cats that had experienced an ATE and recovered from that initial event. This was a way to ensure that we were focused on cats that had a demonstrated tendency for clot formation. The only way to accomplish this was through a multi-center study that had contributions from veterinary intensivists and cardiologists across the US and in the UK. Our primary outcome was focused on recurrence of ATE in the studied cats. Secondary outcomes focused on death from any cause. Once cats had recovered from their ATE and were diagnosed by a cardiologist with heart disease, they were randomized to receive either clopidogrel (18.75 mg PO q 24h) or rivaroxaban (2.5 mg PO q 24h). Our hope was to focus on underlying mechanisms by inhibiting platelet function with the clopidogrel in that group, leaving coagulation function intact, while the rivaroxaban group would retain normal platelet function but have inhibition of the coagulation cascade through factor Xa inhibition. Cats could receive any other medications prescribed by their cardiologist, and these varied somewhat because of the different underlying cardiac diagnoses. The entire duration of the study was 2 years, after which cats were unblinded to their medication and could continue under the guidance of a cardiologist. The study was powered using data from the previous FATCAT trial published by Dr. Dan Hogan, and it was calculated that 45 cats in each group would provide adequate numbers to compare survival between the groups.
What are the main study results?
Of the 45 randomized cats, 17 experienced ATE recurrence: 7 of 19 cats (37%) in the group receiving clopidogrel and 10 of 26 cats (39%) in the rivaroxaban group (P = 1.0). In these cats, median (95% CI) time to ATE recurrence was 663 days (150 to not calculable) in the clopidogrel group and 513 days (242 to not calculable)in the rivaroxaban group (P = .797). So the main results from this aspect of the study is that rivaroxaban performed as well as clopidogrel in terms of prolonging the time to ATE recurrence. Notably, in both groups, more than half of the cats did not have a recurrence, and either survived the entire 2 years of the study or died for a cause unrelated to ATE (as best we could determine). The deaths due to cardiac causes (e.g. progression of cardiac disease) included 12 cats that were euthanized over the course of the study due to congestive heart failure (3 receiving clopidogrel and 7 receiving rivaroxaban), one in the rivaroxaban group due to progression of heart disease, and 2 cats (1 in each group) that died at home of presumed cardiac causes not related to thrombosis.
Were there any unexpected results or challenges during your research?
The main challenge that we encountered was one of enrollment. ATE is obviously a devastating disease, and one that highlights the fact that the cats likely have advanced cardiac disease that will limit survival. we found that many cats that were potentially enrolees were euthanized at presentation, either due to inability to control discomfort, death due to reperfusion injury, or due to the generally poor prognosis for a cat that would have likely progressive cardiac disease. As veterinarians became more comfortable using rivaroxaban during the latter years of the study, we found many prescribing both clopidogrel and rivaroxaban to cats, which then made it difficult to recruit them into our study. As noted above, we had targeted 45 cats in each group but ultimately recruited only 45 total cats, and so the lack of statistical difference between groups may also represent a study that was underpowered to find a difference if one existed.
Takeaways from this study
One take away from this study that impressed me was the relatively long duration of survival for cats in both groups: the median survival time in Dr. Hogan’s FATCAT study for cats receiving clopidogrel was 248 days (95% CI, 137 to 431 days). Our clopidogrel group had median survival of 335 days (95% CI, 150–515) and the rivaroxaban group had median survival of 296 days (95% CI, 209–510). This survival data first indicates that ATE is a survivable condition and with appropriate therapy can have median survival of almost a year and potentially longer, and I would encourage veterinarians not to reflexively euthanize cats with ATE. As noted above, there are a number of very reasonable considerations that support euthanasia of cats with ATE, but they can survive. More recent data from Dr. Guillaumin at Colorado State also indicates that there may be protocols that can be used to promote clot dissolution (e.g. with tissue plasminogen activator infusions) and this may also help to speed recovery in cats affected with ATE.
Another take home, although there is a possibility of type II error, is that clopidogrel and rivaroxaban performed similiarly as single-agent anticoagulants in cats following ATE. At the moment, rivaroxaban is quite costly, at least in the united states, and having some suggestion that the much cheaper clopidogrel is a viable therapy may allow treatment if the owner cannot afford rivaroxaban.
What future directions would you like to explore based on this study?
One obvious direction that results from the presented results is whether cats receiving dual therapy with both rivaroxaban and clopidogrel have any survival benefit. At this point, only case reports have been published using dual therapy, but longer term studies with many more patients will be necessary to determine a benefit for dual therapy. At this point, I would argue that single agent therapy still represents standard of care, but optimally a study comparing single vs dual therapy would be performed.
The other question that is important in this context and which will be even harder to study is the role of one or both drugs in the prevention of ATE in cats with heart disease. As I previously noted, it can be difficult to identify which cats, even among those with heart disease, will develop ATE, and so it would require a study of a very large number of cats with heart disease without (prior to?) developing an ATE to truly determine if anticoagulation in asymptomatic cats (and which type of anticoagulation!) is indicated. Hopefully we will continue to research markers of thrombophilia in cats, whether it be evidence of altered blood flow (e.g. spontaneous echo contrast) seen on echocardiography, or blood testing for procoagulant factors, that will help us better identify cats at risk of ATE so we can have more directed treatment guidelines. At this point, the very good safety profiles of clopidogrel and rivaroxaban combined with the devastating consequences of ATE will likely argue for treatment across the board as long as it is possible to do so.
