Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty II - EPCAT II

Contribution To Literature:

The EPCAT II trial showed that extended-duration treatment with low-dose aspirin is noninferior to low-dose rivaroxaban for thromboprophylaxis among patients undergoing total hip or knee arthroplasty.


The goal of the trial was to compare the safety and efficacy of low-dose aspirin vs. rivaroxaban for extended-duration prophylaxis among patients undergoing total hip or total knee arthroplasty.

Study Design

All patients received rivaroxaban 10 mg for up to 5 days following surgery. Following this, patients were randomized in a 1:1 fashion to either continued rivaroxaban 10 mg (n = 1,717) or aspirin 81 mg daily (n = 1,707) (additional thromboprophylaxis for 9 days for total knee arthroplasty and 30 days for total hip arthroplasty).

  • Total number of enrollees: 3,424
  • Duration of follow-up: 90 days
  • Mean patient age: 62.8 years
  • Percentage female: 52%

Inclusion criteria:

  • Elective unilateral primary or revision hip or knee arthroplasty

Exclusion criteria:

  • Hip or lower limb fracture in the previous 3 months
  • Metastatic cancer
  • Life expectancy <6 months
  • History of major bleeding
  • History of aspirin allergy, active peptic ulcer disease, or gastritis
  • History of significant hepatic disease or any other condition that in the judgment of the investigator precludes the use of rivaroxaban
  • Creatinine clearance <30 ml/min
  • Platelet count <100 x 109 /L
  • Need for long-term anticoagulation due to a pre-existing comorbid condition or due to the development of venous thromboembolism (VTE) following surgery, but prior to randomization
  • Did not or will not receive rivaroxaban postoperatively for VTE prophylaxis
  • Bilateral total hip arthroplasty or simultaneous hip and knee arthroplasty
  • Major surgical procedure within the previous 3 months
  • Requirement for major surgery post-arthroplasty within 90-day period
  • Chronic daily aspirin use with dose >100 mg a day

Other salient features/characteristics:

  • Previous VTE: 2.4%, previous surgery: 3%, cancer: 2.4%
  • Postoperative mechanical compression for thromboprophylaxis: pneumatic compression (51%), graduated stockings (41%), both (8%)
  • Procedure under regional anesthesia: 71%

Principal Findings:

The primary outcome, symptomatic proximal deep-vein thrombosis or pulmonary embolism, for aspirin vs. rivaroxaban: 0.64% vs. 0.7%,  p < 0.001 for noninferiority, p = 0.84 for superiority.

  • Pulmonary embolism: 0.29% vs. 0.35%
  • Proximal deep-vein thrombosis: 0.23% vs. 0.23%

Secondary outcomes:

  • Major bleeding: 0.47% vs. 0.29%, p = 0.42
  • Any bleeding: 1.29% vs. 0.99%, p = 0.43


The results of this important trial indicate that extended-duration treatment with low-dose aspirin is noninferior to low-dose rivaroxaban for thromboprophylaxis among patients undergoing total knee or hip replacement. Overall rates of symptomatic VTE were very low with both strategies; bleeding rates were also similar. Of note, all patients received rivaroxaban 10 mg for 5 days postoperatively. Given the cost differences between the two drugs, this trial has the potential to significantly influence clinical practice and guidelines. In the EPCAT I trial, extended-duration aspirin was noninferior to short-duration low molecular weight heparin (LMWH) for surgical thromboprophylaxis. Interestingly, in the RECORD trials (1-4), rivaroxaban 10 mg was found to be superior to LMWH for the same indication. The trial populations may be somewhat different, and it is unclear if patients at highest risk for VTE events would benefit from rivaroxaban compared with aspirin.

A trend toward higher bleeding rates among the patients who continued long-term aspirin therapy in addition to trial-assigned aspirin serves as a reminder that, whenever possible, we should use daily aspirin doses of <100 mg.


Anderson DR, Dunbar M, Murnaghan J, et al. Aspirin or Rivaroxaban for VTE Prophylaxis After Hip or Knee Arthroplasty. N Engl J Med 2018;378:699-707.

Editorial: Garcia D. Hybrid Strategy to Prevent Venous Thromboembolism After Joint Arthroplasty. N Engl J Med 2018;378:762-3.

Keywords: Anesthesia, Conduction, Anticoagulants, Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Aspirin, Hemorrhage, Heparin, Low-Molecular-Weight, Pulmonary Embolism, Secondary Prevention, Elective Surgical Procedures, Venous Thromboembolism, Venous Thrombosis

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