Prospective Randomized On-X Anticoagulation Clinical Trial - PROACT Xa

Aug 23, 2023
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Artivion, formerly CryoLife, Kennesaw, GA
Date Published:
05/06/2023
Date Updated:
08/23/2023
Original Posted Date:
08/23/2023
References

Contribution To Literature:

The PROACT Xa trial showed that among patients with an On-X mechanical aortic valve implanted ≥3 months earlier, apixaban 5 mg BID did not meet criteria for noninferiority compared with warfarin with a target INR of 2 to 3.

Description:

The goal of the trial was to assess whether apixaban was noninferior to warfarin in preventing valve thrombosis or valve-related thromboembolism in patients with an On-X mechanical aortic valve.

Study Design

Eligible patients were randomized in a 1:1 open-label fashion to either apixaban 5 mg twice daily or warfarin with a target international normalized ratio (INR) of 2.0 to 3.0. Randomization was stratified on the basis of whether the On-X valve was implanted greater or less than 1 year before randomization.

All participants were required to take aspirin 81 mg daily or have a documented contraindication to aspirin use.

  • Total number of enrollees: 863
  • Duration of follow-up: 13.4 months (median)
  • Mean patient age: 55.5 years
  • Percentage female: 24%

Inclusion criteria:

  • ≥18 years of age
  • Underwent implantation of an On-X mechanical aortic valve ≥3 months before they were randomly assigned
  • Able to receive warfarin at a targeted INR range between 2.0 and 3.0

Other salient features/characteristics:

  • Valve size ≤21 mm: 25%
  • Reoperation of aortic valve: 15%
  • Prior stroke/transient ischemic attack: 9.5%
  • Atrial fibrillation: 24%

Principal Findings:

The trial was terminated early by the Data and Safety Monitoring Board due to higher risk of thromboembolic events in participants randomly assigned to apixaban than in those assigned to warfarin.

The primary efficacy outcome (valve thrombosis or valve-related thromboembolism) for apixaban vs. warfarin: 4.2%/patient-year (PY) vs. 1.3%/PY; rate difference: 2.9 (95% confidence interval 0.8-5.0). This did not meet criteria for noninferiority.

  • Valve-related thrombosis for apixaban vs. warfarin: 0.6%/PY vs. 0
  • Valve-related thromboembolism for apixaban vs. warfarin: 3.5% vs. 1.3%/PY
  • Primary safety outcome (major bleeding) for apixaban vs. warfarin: 3.6% vs. 4.5%/PY

Interpretation:

The results of this trial indicate that among patients with an On-X mechanical aortic valve implanted ≥3 months earlier, apixaban 5 mg BID did not meet criteria for noninferiority compared with warfarin with a target INR of 2 to 3. Apixaban resulted in more valve thrombosis or valve-related thromboembolic events than warfarin, leading to the early termination of the PROACT Xa trial. Major bleeding events were similar. The excess in thromboembolic events with apixaban was not attributable to participants with a recent valve implant, inappropriate apixaban dosing, or apixaban interruption.

A previous study (PROACT) in patients with On-X valves in the aortic position suggested that, compared with a target INR of 2.0 to 3.0, a lower target INR of 1.5 to 2.0 with warfarin results in similar rates of valve thrombosis or thromboembolism and lower rates of bleeding. This lower target INR for the On-X valve has been incorporated into clinical practice guideline recommendations.

References:

Wang TY, Svensson LG, Wen J, et al., on behalf of the PROACT Xa Investigators. Apixaban or Warfarin in Patients with an On-X Mechanical Aortic Valve. NEJM Evid 2023;May 6:[Epublished].

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Valvular Heart Disease, Vascular Medicine, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and VHD, Interventions and Structural Heart Disease, Interventions and Vascular Medicine

Keywords: Anticoagulants, Aortic Valve, Aspirin, Cardiac Surgical Procedures, Heart Valve Diseases, Heart Valve Prosthesis, Hemorrhage, International Normalized Ratio, Secondary Prevention, Thromboembolism, Vascular Diseases, Venous Thrombosis, Warfarin


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