Prevention of Venous Thromboembolism after Total Hip or Knee Replacement

Studies comparing aspirin with anticoagulants for venous thromboembolism (VTE) prophylaxis after total hip or knee arthroplasty have had conflicting results. In a comparative-effectiveness noninferiority trial, we randomly assigned patients undergoing elective hip or knee arthroplasty to receive aspirin (81 mg twice daily), warfarin (to a target international normalized ratio of 2.0), or rivaroxaban (10 mg daily) for 30 days. The composite primary effectiveness outcome (death from any cause or symptomatic VTE) and primary safety outcome (bleeding, reoperation for wound problems, or myocardial infarction) were evaluated through 6 months in a blinded fashion. The noninferiority margin for the risk difference was 0.69 percentage points. Among 18,883 participants who had undergone randomization, 15,317 (7214 with hip arthroplasty and 8103 with knee arthroplasty) were included in the primary per-protocol analysis. A primary effectiveness outcome event occurred in 77 of 6090 participants (1.26%) in the aspirin group, in 52 of 4231 (1.23%) in the warfarin group, and in 47 of 4996 (0.94%) in the rivaroxaban group; a primary safety outcome event occurred in 177 (2.91%), 142 (3.36%), and 174 (3.48%), respectively. In pairwise comparisons, 6-month risks of a primary effectiveness outcome event were 1.24% and 0.94% for aspirin versus rivaroxaban (difference, 0.30 percentage points; 95% confidence interval [CI], -0.20 to 0.81); 1.24% and 1.01% for aspirin versus warfarin (difference, 0.23 percentage points; 95% CI, -0.34 to 0.81); and 1.13% and 1.10% for warfarin versus rivaroxaban (difference, 0.03 percentage points; 95% CI, -0.57 to 0.63). Risks of a primary safety outcome event were 3.70% and 3.02% for rivaroxaban versus aspirin (difference, 0.68 percentage points; 95% CI, -0.04 to 1.41); 3.65% and 2.88% for warfarin versus aspirin (difference, 0.77 percentage points; 95% CI, -0.04 to 1.58); and 3.59% and 3.61% for rivaroxaban versus warfarin (difference, -0.02 percentage points; 95% CI, -0.89 to 0.85). Intention-to-treat analyses yielded similar results. Aspirin prophylaxis after total hip or knee arthroplasty was not noninferior to rivaroxaban or warfarin with respect to death or symptomatic VTE. Warfarin and rivaroxaban were not noninferior to aspirin for safety. (Funded by the Patient-Centered Outcomes Research Institute; PEPPER ClinicalTrials.gov number, NCT02810704.).