Aspirin Alone Noninferior After Hip or Knee Arthroplasty

Key Takeaways

• After total hip or total knee arthroplasty, aspirin alone was not inferior to rivaroxaban followed by aspirin for preventing symptomatic venous thromboembolism.
• 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.

The first days after total hip or knee arthroplasty are a narrow postoperative window in which thromboprophylaxis must balance regimen simplicity with protection against clinically important clotting events. A practical unresolved question has been whether aspirin can start on postoperative day 1 rather than only after a short course of a direct oral anticoagulant such as rivaroxaban. A large randomized comparison tested that question after joint replacement surgery.

Investigators conducted the multicenter, double-blind, randomized, controlled trial. 5,429 patients after total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to once-daily 81 mg aspirin or 10 mg oral rivaroxaban for the first 5 postoperative days.

Both groups then received 81 mg aspirin for 9 additional days after TKA and 30 additional days after THA, with follow-up through 90 days. The primary effectiveness outcome was symptomatic venous thromboembolism (VTE), defined as proximal deep-vein thrombosis or pulmonary embolism, and bleeding complications were the primary safety outcome; the prespecified noninferiority margin was 0.7 percentage points.

Symptomatic VTE developed in 13 of 2718 patients assigned to aspirin alone and in 12 of 2647 assigned to rivaroxaban followed by aspirin. The reported risk difference was 0.02 percentage points with a 95% confidence interval (CI) of -0.34 to 0.39. Investigators concluded from that comparison that aspirin alone met the trial’s noninferiority criterion for prevention of symptomatic VTE after arthroplasty.

Interpretation remains limited to the arthroplasty population enrolled in this randomized trial rather than to other surgical settings or unreported subgroups.

Major bleeding or clinically relevant nonmajor bleeding occurred in 45 of 2718 patients (1.66%) in the aspirin-alone group and 54 of 2647 patients (2.04%) in the rivaroxaban–aspirin group, for a risk difference of −0.38 percentage points (95% CI, −1.11 to 0.34). The authors concluded that there was no clinically relevant difference in bleeding events between strategies.

In this study, aspirin alone was not inferior to rivaroxaban followed by aspirin for prevention of symptomatic VTE after total hip and total knee arthroplasty. The authors also reported no clinically relevant difference in bleeding events between the 2 approaches. This remains a randomized noninferiority finding confined to the postoperative arthroplasty setting.

Clinician Questions

Was aspirin compared with rivaroxaban for the full prophylaxis course after hip or knee arthroplasty?

No. The randomized difference was limited to the first 5 postoperative days, when patients received either 81 mg aspirin or 10 mg oral rivaroxaban once daily, and all patients then received 81 mg aspirin for 9 additional days after total knee arthroplasty or 30 additional days after total hip arthroplasty. The trial therefore did not compare 2 entirely different extended prophylaxis regimens.

What bleeding detail was available for aspirin-alone prophylaxis after total hip or knee arthroplasty?

Bleeding complications were the primary safety outcome, and the authors concluded that there was no clinically relevant difference between aspirin alone and rivaroxaban followed by aspirin after total hip or knee arthroplasty.

Which patients does this arthroplasty noninferiority finding directly apply to?

The finding directly applies to patients undergoing total hip arthroplasty or total knee arthroplasty in this multicenter, double-blind, randomized trial. It should not be extended here to other surgeries or to unreported subgroups because the abstract does not provide subgroup analyses.