71. 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
Weill Cornell Medical Center
New York, NY
United States - Contact Me
Professor and Chairman, Department of Cardiothoracic Surgery, Weill Cornell Medicine
Cardiothoracic Surgeon-in-Chief, New York Presbyterian/Weill Cornell Medical Center
Cleveland Clinic
Cleveland, OH
United States - Contact Me
Dr. Svensson is the Chairman of the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic and served on the Cleveland Clinic Health System Operations Council. Dr. Svensson is an internationally known cardiovascular and thoracic surgeon. His research has led to many innovative surgical treatments and techniques. He is a Professor of Surgery at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. Dr. Svensson previously served on the AATS Council, has Chaired the AATS Guidelines Committee. He has chaired multispecialty guidelines writing committees for endovascular treatment with stents for the thoracic aorta, aortic valve surgery, and for the treatment of thoracic aortic disease.Dr. Svensson was born in Barberton, South Africa. He completed his undergraduate work at Treverton College in Mooi River, South Africa. He earned his medical degree and PhD in blood flow pathophysiology from the University of Witwatersrand in Johannesburg, where he received numerous fellowships and awards. He received his training in cardiology and general surgery at the Johannesburg Hospital, South Africa, and his training in cardiothoracic surgery at Cleveland Clinic, Cleveland, OH, for which he received a fellowship. He also completed a cardiovascular surgery fellowship and residency at Baylor College of Medicine in Houston, TX. In 2005, Dr. Svensson was named King James IV Professor of Surgery of the Royal College of Surgeons of Edinburgh. His academic appointments have included Chief of Cardiothoracic Surgery at the Veterans Administration Hospital in Houston, TX; Clinical Instructor in Surgery at Harvard Medical School, Boston, MA; Clinical Professor of Cardiothoracic Surgery at Tufts University, Boston; and Assistant Professor of Surgery at Baylor College of Medicine, Houston.
Description
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.