PROACT Xa: A Multicenter, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Apixaban vs. Warfarin in Patients with a Mechanical Bileaflet Aortic Heart Valve

71 

Abstract Submission 

Lars Svensson (1), Tracy Y. Wang (2), Jun Wen (2), Andrew Vekstein (3), Marc Gerdisch (4), Douglas Johnston (1), Renato D. Lopes (5), Alma Chavez (2), Marc Ruel (6), Eugene Blackstone (1), Richard C. Becker (7), Vinod Thourani (8), John Puskas (9), David Cable (10), John Elefteriades (11), Alberto Pochettino (12), J. Alan Wolfe (13), Allen Graeve (14), Ibrahim Sultan (15), Ashraf Sabe (16), Hector Michelena (17), John Alexander (3)

(1) Cleveland Clinic, Cleveland, OH, (2) Duke Clinical Research Institute, Durham, NC, (3) Duke University Medical Center, Durham, NC, (4) Franciscan Health Heart Center, Indianapolis, IN, (5) Division of Cardiology, Duke Clinical Research Institute, Durham, NC, (6) University of Ottawa Heart Institute, Ottawa, ON, (7) University of Cincinnati Heart, Lung & Vascular Institute, Cincinnati, OH, (8) Piedmont Heart Institute, Atlanta, GA, (9) Mount SInai Morningside (St. Luke's), New York, NY, (10) Cardiac Surgery Associates, SC, Upper Peninsula Health System, Marquette, MI, (11) Yale New Haven Hospital, New Haven, CT, (12) Mayo Clinic, Rochester, MN, (13) N/A, Atlanta, GA, (14) Multicare Tacoma General, Tacoma, WA, (15) University of Pittsburgh Medical Center, Pittsburgh, PA, (16) Brigham and Women's Hospital, Boston, MA, (17) N/A, Rochester, MN

*Lars Svensson    -  Contact Me
Cleveland Clinic

Tracy Y. Wang    -  Contact Me
Duke Clinical Research Institute

Jun Wen    -  Contact Me
Duke Clinical Research Institute

Andrew Vekstein    -  Contact Me
Duke University Medical Center

*Marc Gerdisch    -  Contact Me
Franciscan Health Heart Center

*Douglas Johnston    -  Contact Me
Cleveland Clinic

Renato D. Lopes    -  Contact Me
Division of Cardiology, Duke Clinical Research Institute

Alma Chavez    -  Contact Me
Duke Clinical Research Institute

*Marc Ruel    -  Contact Me
University of Ottawa Heart Institute

*Eugene Blackstone    -  Contact Me
Cleveland Clinic

Richard C. Becker    -  Contact Me
University of Cincinnati Heart, Lung & Vascular Institute

*Vinod Thourani    -  Contact Me
Piedmont Heart Institute

*John Puskas    -  Contact Me
Mount SInai Morningside (St. Luke's)

David Cable    -  Contact Me
Cardiac Surgery Associates, SC, Upper Peninsula Health System

*John Elefteriades    -  Contact Me
Yale New Haven Hospital

Alberto Pochettino    -  Contact Me
Mayo Clinic

J. Alan Wolfe    -  Contact Me
N/A

Allen Graeve    -  Contact Me
Multicare Tacoma General

*Ibrahim Sultan    -  Contact Me
University of Pittsburgh Medical Center

Ashraf Sabe    -  Contact Me
Brigham and Women's Hospital

Hector Michelena    -  Contact Me
N/A

John Alexander    -  Contact Me
Duke University Medical Center

*Lars Svensson    -  Contact Me
Cleveland Clinic

Objective: Vitamin K antagonists are the only approved oral anticoagulants to prevent valve thrombosis and thromboembolism in patients with mechanical heart valves. The PROACT Xa trial assessed whether patients with bileaflet aortic valves can be safely anticoagulated with apixaban, a direct factor Xa inhibitor, as an alternative to warfarin.

Methods: PROACT Xa was a randomized, multicenter, open-label trial comparing apixaban with warfarin in patients with bileaflet carbon aortic valves. Patients at least 3 months out from AVR were randomized 1:1 to receive apixaban 5 mg twice daily or warfarin with a target INR of 2–3. Primary efficacy outcome is composite of valve thrombosis and valve-related thromboembolism; primary safety outcome is major bleeding. All events are independently adjudicated by a clinical events committee blinded to study drug assignment. A planned sample size of 1000 patients allowed >90% power to assess noninferiority of apixaban to warfarin, assuming the primary efficacy outcome occurs in warfarin-treated patients at a rate of 1.75%/pt-yr with an absolute noninferiority margin of 1.75%/pt-yr. A co-primary efficacy analysis was to compare hazard rate for the apixaban arm to twice the objective performance criterion (3.4%/pt-year).

Results: A total of 863 patients from 60 sites were randomized from May 2020–Sep 2022. Enrolled patients had a median age of 56 years; 24% were female. Among participants, 46% had AVR in the 12 months prior to randomization, 17% had AVR along with an aortic root graft, and 16% were reoperations on the aortic valve. Most (93%) patients received aspirin 81 mg daily with the assigned anticoagulant. Median time in therapeutic range for warfarin-treated patients was 71.4% [55.1, 82.9]. On Sep 21, 2022, the DSMB recommended discontinuation of enrollment based on observed higher rate of thromboembolic events in patients randomized to apixaban than warfarin. All patients were transitioned off study drug and will be followed for at least 30 days after study drug discontinuation for all pre-specified outcomes.

Conclusions: Complete data on primary efficacy and safety outcomes will be available for presentation at the AATS Meeting in May 2023. While final data collection is ongoing, the PROACT Xa trial is likely to conclude that apixaban does not provide a safe alternative to warfarin for the prophylaxis of valve thrombosis or valve-related thromboembolism in patients with bileaflet mechanical aortic valves.

Aortic Valve