Background
EPCAT III. Multicenter, double-blind, randomised noninferiority trial. N=5429 patients undergoing total hip or total knee arthroplasty. Compares aspirin alone versus an initial 5-day rivaroxaban course followed by aspirin for symptomatic VTE thromboprophylaxis.
Results
Interventions and follow up: Arm A: Aspirin 81 mg PO daily for first 5 days, then aspirin 81 mg daily (9 more days after knee, 30 more days after hip) (n=2718)
Arm B: Rivaroxaban 10 mg PO daily for first 5 days, then aspirin 81 mg daily (same durations) (n=2647)
Primary effectiveness endpoint: symptomatic VTE (proximal DVT or PE) at 90 days
Primary safety endpoint: major or clinically relevant non-major bleeding
Noninferiority margin: 0.7 percentage points
Results: Symptomatic VTE: 0.48% (13/2718) vs 0.45% (12/2647); risk difference 0.02 pp, 95% CI −0.34 to 0.39, P<.001 for noninferiority.
Major/CRNM bleeding: 1.66% vs 2.04%; risk difference −0.38 pp, 95% CI −1.11 to 0.34.
Arm B: Rivaroxaban 10 mg PO daily for first 5 days, then aspirin 81 mg daily (same durations) (n=2647)
Primary effectiveness endpoint: symptomatic VTE (proximal DVT or PE) at 90 days
Primary safety endpoint: major or clinically relevant non-major bleeding
Noninferiority margin: 0.7 percentage points
Results: Symptomatic VTE: 0.48% (13/2718) vs 0.45% (12/2647); risk difference 0.02 pp, 95% CI −0.34 to 0.39, P<.001 for noninferiority.
Major/CRNM bleeding: 1.66% vs 2.04%; risk difference −0.38 pp, 95% CI −1.11 to 0.34.
Adverse events
Major or CRNM bleeding: 1.66% (aspirin) vs 2.04% (rivaroxaban-aspirin).
Symptomatic VTE (90 d): 0.48% vs 0.45%.
No clinically relevant between-group difference in bleeding.
Symptomatic VTE (90 d): 0.48% vs 0.45%.
No clinically relevant between-group difference in bleeding.
Conclusions
Aspirin alone was noninferior to a rivaroxaban-then-aspirin strategy for preventing symptomatic VTE after total hip or knee arthroplasty, with no clinically relevant difference in bleeding. Supports simple, low-cost aspirin monotherapy as thromboprophylaxis.
Key Limitations
Very low overall VTE event rate limits power for subgroups; symptomatic (not screening-detected) VTE endpoint; all patients received aspirin after day 5, so the trial isolates the added value of an initial rivaroxaban lead-in rather than comparing two fully distinct regimens; high-risk patients underrepresented.
Clinical Context
Builds directly on EPCAT II (2018, NEJM), which showed aspirin after a 5-day rivaroxaban course was effective; EPCAT III removes the rivaroxaban lead-in entirely. ASH and AAOS guidance already accept aspirin as an acceptable thromboprophylaxis option after arthroplasty. Reinforces aspirin-only prophylaxis as an inexpensive, oral, guideline-concordant standard.