Aspirin Alone Gets the Job Done for Clot Prevention After Joint Surgery

Key Takeaways - A randomized trial tested once-daily thromboprophylaxis with aspirin or rivaroxaban for the first 5 days after total hip or total knee arthroplasty, followed by aspirin alone. - Aspirin alone came out noninferior for preventing symptomatic venous thromboembolism, with no clinically relevant difference in bleeding events between groups. - The trial supports an aspirin-alone strategy for people at standard risk, potentially indicating a cheaper and simpler approach to prophylaxis against blood clots. An aspirin-only approach to postoperative prophylaxis after arthroplasty was as effective and safe as upfront rivaroxaban (Xarelto), according to the EPCAT III randomized trial. Aspirin-only prophylaxis met noninferiority criteria for preventing symptomatic venous thromboembolism (VTE), compared with rivaroxaban then aspirin after total hip or total knee arthroplasty, reported investigators led by Sudeep Shivakumar, MD, of Dalhousie University and Nova Scotia Health Authority in Halifax. Following 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 nonmajor 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 published in the New England Journal of Medicine and presented at the International Society on Thrombosis and Haemostasis annual congress. "Aspirin is a commonly available and inexpensive oral medication that has the potential to simplify postsurgical 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 II trial previously showed that switching to aspirin after 5 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 individualized strategy should be considered if a patient is identified as being at higher risk for VTE," study authors cautioned. Indeed, the trial had excluded people with previous VTE, a hip or lower-limb fracture during the previous 3 months, and metastatic cancer. EPCAT III was conducted at 15 university-affiliated health centers 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 5 days after total hip or total knee arthroplasty. All individuals received further thromboprophylaxis with 81 mg of aspirin daily for 9 additional days after knee arthroplasty and for 30 additional days after hip arthroplasty. The noninferiority 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-randomized, crossover, noninferiority 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 generalizability 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.