NEJM - 2026-07-12 - Journal Article
Rivaroxaban Then Aspirin vs. Aspirin Alone after Total Hip or Knee Arthroplasty.
Shivakumar S, Matino D, Zukor D, Kahn SR, Vincent G, Mundi R, Vendittoli PA, Refaei M, Bohm E, Tanzer M, Pelet S, Richardson G, Powell J, Ikesaka R, Douketis J, Ward S, Kim P, Mann S, Pleasance S, Cormier J, Andreou P, Matheson K, Theriault C, West C, Anderson D, Gross PL, EPCAT III Trial Investigators
Topics
Key Takeaway
Aspirin alone (81 mg daily) was noninferior to rivaroxaban-then-aspirin for symptomatic VTE prevention after THA/TKA, with VTE rates of 0.48% vs. 0.45% (risk difference 0.02 percentage points).
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Summary
EPCAT III randomized 5429 THA/TKA patients to aspirin alone (81 mg daily) vs. rivaroxaban 10 mg for 5 days followed by aspirin for the remainder of the prophylaxis period. Symptomatic VTE (proximal DVT or PE) occurred in 0.48% of the aspirin-alone group vs. 0.45% in the rivaroxaban-aspirin group, meeting the prespecified noninferiority margin of 0.7 percentage points (p<0.001). Major or clinically relevant nonmajor bleeding was 1.66% vs. 2.04%, with no statistically significant difference.
Key Limitation
The trial enrolled patients deemed suitable for aspirin prophylaxis by their surgeons, introducing selection bias that excludes higher-risk patients (prior VTE, hypercoagulable states, malignancy) to whom these results cannot be generalized.
Original 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 multicenter, double-blind, randomized, 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 5 days after total hip or total knee arthroplasty. All the patients then received further thromboprophylaxis with 81 mg of aspirin daily for 9 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 noninferiority margin for aspirin alone as compared with rivaroxaban-aspirin was 0.7 percentage points.
RESULTS
A total of 5429 patients underwent randomization. Venous thromboembolism developed in 13 of 2718 patients (0.48%) in the aspirin-alone group and in 12 of 2647 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 noninferiority). Major bleeding or clinically relevant nonmajor 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. (Funded by the Canadian Institutes of Health Research; EPCAT III ClinicalTrials.gov number, NCT04075240.).