Rivaroxaban Then Aspirin vs. Aspirin Alone after Total Hip or Knee Arthroplasty

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.).