Researchers found that after a randomised trial testing once-daily thromboprophylaxis with aspirin or rivaroxaban for the first five days after total hip or total knee arthroplasty, followed by aspirin alone, aspirin alone emerged as non-inferior for preventing symptomatic venous thromboembolism, with no clinically relevant difference in bleeding events between groups.
MedPage Today reports that the trial supports an aspirin-alone strategy for people at standard risk, potentially indicating a cheaper and simpler approach to prophylaxis against blood clots.
The Canadian team suggested the aspirin-only approach to postoperative prophylaxis after arthroplasty was as effective and safe as upfront rivaroxaban (Xarelto), according to their EPCAT III randomised trial.
The findings, reported in The New England Journal of Medicine by the investigators, led by Sudeep Shivakumar, MD, of Dalhousie University and Nova Scotia Health Authority in Halifax, showed that aspirin-only prophylaxis met non-inferiority criteria for preventing symptomatic venous thromboembolism (VTE), compared with rivaroxaban then aspirin after total hip or total knee arthroplasty.
After arthroplasty, the incidence of symptomatic VTE over 90 days – counting proximal deep vein thrombosis or pulmonary embolism – reached 0.48% with aspirin alone and a similar 0.45% with rivaroxaban-aspirin (risk difference 0.02, 95% CI -0.34 to 0.39).
As for safety, there was no clinically meaningful difference in major bleeding or clinically relevant non-major bleeding events between the two groups (1.66% vs 2.04%, risk difference -0.38%, 95% CI -1.11 to 0.34) in the trial of nearly 5 500 people.
EPCAT III was also recently presented at the International Society on Thrombosis and Haemostasis annual congress.
“Aspirin is a commonly available and inexpensive oral medication with the potential to simplify post-surgical prophylaxis for providers and patients, and the results of our trial provide strong evidence for clinical decision making when considering an aspirin-alone strategy,” Shivakumar and colleagues wrote.
Over the past decade, direct anticoagulants (DOACs) including apixaban (Eliquis) and rivaroxaban, have become popular for preventing VTE after arthroplasty, alongside the conventional anticoagulant warfarin.
Aspirin, belonging to the antiplatelet class, has also been on the rise for joint replacement, albeit with a less established evidence base.
The researchers noted that aspirin after an initial short course of rivaroxaban had already been shown to be safe and effective for the preventing VTE after total hip or total knee arthroplasty: the EPCAT 11 TRIAL previously showed that switching to aspirin after five days of rivaroxaban was at least as safe and effective as rivaroxaban alone.
In EPCAT III, the message appears to be that some arthroplasty patients can do without the DOAC altogether.
However, one caveat was that the study population had a STOP-VTE score of 1.1 on average, indicating standard risk, with only 3.4% of the patients classified as being at high risk. “As such, an individualised strategy should be considered if a patient is identified as being at higher risk for VTE,” the study authors cautioned.
Indeed, the trial had excluded people with previous VTE, a hip or lower-limb fracture during the previous three months, and metastatic cancer.
EPCAT III was conducted at 15 university-affiliated health centres in Canada. The double-blind trial had 5 429 participants undergoing primary arthroplasty or revision arthroplasty of the hip or knee.
Patients were enrolled from 2021 to 2026; they had a mean age of 66.5 years and were 56.9% men. The majority underwent knee arthroplasty (53.1%), and the rest hip arthroplasty. Cases were by and large primary arthroplasties (96.6%), the small remainder being revision operations (3.4%). Postoperative use of compression stockings reached 19.5%. Long-term aspirin use before surgery was 8.0%.
Study regimens were once-daily thromboprophylaxis with either 81 mg of aspirin or 10 mg of oral rivaroxaban for the first five days after total hip or total knee arthroplasty. All individuals received further thromboprophylaxis with 81 mg of aspirin daily for nine additional days after knee arthroplasty and for 30 additional days after hip arthroplasty.
The non-inferiority margin for aspirin-only versus rivaroxaban-aspirin was set at 0.7 percentage points regarding the composite primary effectiveness endpoint. This was met with a statistical significance of P<0.001, according to Shivakumar and colleagues.
An analysis that expanded the composite effectiveness outcome to include distal deep vein thrombosis still came out even between aspirin alone and rivaroxaban-aspirin (1.03% vs 0.87%, risk difference 0.16%, 95% CI -0.36 to 0.68).
This was a reassuring finding in the aftermath of 2022’s CRISTAL study. In that cluster-randomised, crossover, non-inferiority trial, aspirin monotherapy was compared with enoxaparin in patients undergoing hip or knee arthroplasty, and the trial was ultimately stopped early after an interim analysis showed excess symptomatic VTE in the aspirin group, driven by an increased risk of distal deep vein thrombosis.
Nonetheless, the present trial had limitations related to its generalisability and lack of demographic data on race or ethnicity, among others.
“The event rates in our trial were lower than those in some previous trials that assessed the use of aspirin alone in this population,” Shivakumar’s team noted.
Study details
Rivaroxaban Then Aspirin vs. Aspirin Alone after Total Hip or Knee Arthroplasty
Sudeep Shivakumar, Davide Matino, David Zukor et al for the EPCAT III Trial Investigators
Published in The New England Journal of Medicine on 12 July 2026
Abstract
Background
Aspirin after an initial short course of rivaroxaban has been shown to be safe and effective for the prevention of venous thromboembolism after total hip or total knee arthroplasty, but uncertainty remains about the use of aspirin alone.
Methods
In this multicentre, double-blind, randomised, controlled trial, we assigned patients to receive once-daily thromboprophylaxis with either 81 mg of aspirin or 10 mg of oral rivaroxaban for the first five days after total hip or total knee arthroplasty. All patients then received further thromboprophylaxis with 81 mg of aspirin daily for nine additional days after knee arthroplasty and for 30 additional days after hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism, which consisted of either proximal deep-vein thrombosis or pulmonary embolism (primary effectiveness outcome), and for bleeding complications (primary safety outcome). The non-inferiority margin for aspirin alone as compared with rivaroxaban–aspirin was 0.7 percentage points.
Results
A total of 5 429 patients underwent randomisation. Venous thromboembolism developed in 13 of 2 718 patients (0.48%) in the aspirin-alone group and in 12 of 2 647 patients (0.45%) in the rivaroxaban–aspirin group (risk difference, 0.02 percentage points; 95% confidence interval [CI], −0.34 to 0.39; P<0.001 for non-inferiority). Major bleeding or clinically relevant non-major bleeding events occurred in 45 of 2718 patients (1.66%) in the aspirin-alone group and in 54 of 2647 patients (2.04%) in the rivaroxaban–aspirin group (risk difference, −0.38%; 95% CI, −1.11 to 0.34).
Conclusions
After total hip and total knee arthroplasty, the use of aspirin alone was not inferior to a strategy of using rivaroxaban followed by aspirin for the prevention of symptomatic venous thromboembolism, with no clinically relevant difference in bleeding events.
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Aspirin as good as Heparin in preventing blood clots – US trial
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