Dr. Puskas Presents Interim Results of New Design Mechanical Heart Valve Trial at AATS Meeting

May 2013

Representing a network of investigators from 36 cardiothoracic surgical centers in the U.S. and Europe, Dr. John Puskas, professor of surgery and associate chief, division of cardiothoracic surgery, Emory University School of Medicine, reported preliminary data from the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) at the 93rd Annual Meeting of the American Association for Thoracic Surgery on May 6, 2013.

Under FDA investigational device exemption, the trial is evaluating whether patients implanted with a newer generation mechanical heart valve, manufactured by On-X Life Technologies, can be safely maintained with reduced levels of such anticoagulation drugs as warfarin, which are prescribed to prevent blood clots from developing on or around the valve but can increase risk of excessive bleeding. The trial's reduced anticoagulation is less aggressive than what has previously been recommended by the American Heart Association and American College of Cardiology.

For more than 40 years, patients under 65 years of age requiring heart valve replacement have had to choose between either a mechanical valve that offers life-long durability but requires aggressive warfarin anticoagulation, or a biological (cow or pig) valve that will wear out in 10-20 years but does not require anticoagulation.

The interim report shows that the use of the On-X mechanical aortic valve combined with lower dose anticoagulation therapy and low-dose aspirin, resulted in a reduction of 55 to 60% of the incidence of adverse bleeding events without notable increases in stroke, transient ischemic attack, or total neurological events.

"Several design features of the On-X valve differ from earlier mechanical valves, resulting in more laminar flow of blood through the valve, lower pressure gradients, smaller regurgitant closing volumes, and less hemolysis," says Dr. Puskas. "If longer term follow-up confirms what we've found so far, guidelines for anticoagulation could be re-written and patients may enjoy a more favorable trade-off between bleeding and clotting complications after mechanical valve replacement."

As part of the PROACT trial, a control group of patients received standard treatment of warfarin administered to maintain a target range of the International Normalized Ratio (INR) of 2.0-3.0. The second treatment group received low-dose warfarin, targeting an INR of 1.5-2.0. 

From June 2006 until October 2009, 375 Aortic Valve Replacement (AVR) patients were randomized into control (190) and treatment (185) groups three months after surgery. All patients had received standard therapy for the first three months, including 81 mg aspirin daily. Mean age was 55.8 years in the control group and 54.1 years in the treatment group. Approximately 80% of the patients were male and 93% were in sinus rhythm before valve replacement. Patients were followed for an average of 3.82 years. The treatment group experienced significantly lower major bleeding rates.

"Anticoagulation may be safely reduced in AVR patients after implantation of this approved bileaflet mechanical prosthesis," Dr. Puskas concluded. "In combination with low-dose aspirin, this therapy resulted in significantly lower risk of bleeding than customary aggressive anticoagulation, without significant increase in clots or strokes."