Research Summary

Aspirin Alone Noninferior to Rivaroxaban Followed by Aspirin After Hip or Knee Arthroplasty

Anthony Calabro, MA

Key Highlights

  • Symptomatic proximal deep-vein thrombosis or pulmonary embolism occurred in 0.48% of patients receiving aspirin alone and 0.45% receiving rivaroxaban followed by aspirin.
  • Aspirin alone met the prespecified noninferiority criterion, with a risk difference of 0.02 percentage points.
  • Major or clinically relevant nonmajor bleeding occurred in 1.66% of the aspirin-alone group and 2.04% of the rivaroxaban–aspirin group.
  • Most participants were classified as being at standard risk for postoperative venous thromboembolism.

Aspirin alone was noninferior to an initial 5-day course of rivaroxaban followed by aspirin for preventing symptomatic venous thromboembolism (VTE) after total hip or total knee arthroplasty, according to results published in The New England Journal of Medicine. Bleeding outcomes also did not differ in a clinically relevant manner between the thromboprophylaxis strategies.

The multicenter EPCAT III trial was conducted at 15 university-affiliated health centers in Canada. Investigators enrolled patients undergoing elective unilateral primary or revision total hip or knee arthroplasty and randomly assigned them to receive once-daily thromboprophylaxis with either aspirin 81 mg or oral rivaroxaban 10 mg during the first 5 postoperative days.

After day 5, all patients received aspirin 81 mg daily for an additional 9 days following knee arthroplasty or for 30 days following hip arthroplasty. Patients were followed for 90 days. The primary effectiveness outcome was symptomatic proximal deep-vein thrombosis (DVT) or pulmonary embolism (PE), and the primary safety outcome was major bleeding or clinically relevant non-major bleeding. The prespecified noninferiority margin was 0.7 percentage points.

Study Findings

A total of 5,429 patients underwent randomization, and 5,365 were included in the modified intention-to-treat analysis. The mean patient age was 66.5 years, 56.9% were women, 46.9% underwent total hip arthroplasty, and 53.1% underwent total knee arthroplasty.

Symptomatic proximal DVT or PE occurred in 13 of 2,718 patients receiving aspirin alone and 12 of 2,647 receiving rivaroxaban followed by aspirin, corresponding to event rates of 0.48% and 0.45%, respectively. The risk difference was 0.02 percentage points (95% CI, −0.34 to 0.39; P < .001 for noninferiority).

Major bleeding or clinically relevant nonmajor bleeding occurred in 45 patients in the aspirin-alone group and 54 patients in the rivaroxaban–aspirin group, for rates of 1.66% and 2.04%, respectively. The risk difference was −0.38 percentage points (95% CI, −1.11 to 0.34).

Major bleeding occurred in 0.44% and 0.30% of patients, respectively, while clinically relevant non-major bleeding occurred in 1.21% and 1.74%. Four surgical-site bleeding events requiring reoperation occurred, all in the rivaroxaban–aspirin group.

Clinical Implications

According to the study authors, aspirin alone was as effective and safe as initial rivaroxaban followed by aspirin. It may simplify postoperative thromboprophylaxis for clinicians and patients because aspirin is inexpensive, widely available, and administered orally.

The authors cautioned that 96.6% of participants were classified as at standard VTE risk and recommended considering an individualized strategy for patients at higher risk. The study limitations included an exclusively Canadian study population, possible underrepresentation of Black patients, and limited generalizability of findings related to compression stockings and anesthesia, as those analyses were not prespecified or adequately powered.

Expert Commentary

“We found that a strategy of using aspirin alone was not inferior to a strategy of using rivaroxaban followed by aspirin for the prevention of proximal deep-vein thrombosis or pulmonary embolism after total hip or total knee arthroplasty, with no clinically meaningful difference in bleeding events,” the researchers concluded.

Reference
Shivakumar S, Matino D, Zukor D, et al; EPCAT III Trial Investigators. Rivaroxaban then aspirin vs aspirin alone after total hip or knee arthroplasty. N Engl J Med. Published online July 12, 2026. doi:10.1056/NEJMoa2603649