News | June 20, 2014

Low-dose Anticoagulation Therapy Can Be Used Safely With New Design Mechanical Heart Valve

Findings from Phase One of the PROACT randomized clinical trial published in The Journal of Thoracic and Cardiovascular Surgery

June 20, 2014 — Less aggressive anticoagulation therapy, combined with low-dose aspirin, can be used safely in conjunction with a newer generation mechanical heart valve. These findings from the first phase of a randomized clinical trial are published in The Journal of Thoracic and Cardiovascular Surgery, an official publication of the American Association for Thoracic Surgery.

Patients under 65 years of age requiring heart valve replacement have had to choose between a mechanical valve that may last a lifetime but requires aggressive anti-clotting treatment with warfarin, and a biological (cow or pig) valve that does not require warfarin treatment but will need replacement in 10-20 years. Aggressive anti-clotting treatment is accompanied by significant risk of bleeding, while inadequate treatment can result in an increased incidence of stroke.

Therefore, the choice between valve types for physicians and patients narrows to one of avoidance of the risk, pain and costs of reoperation for valve obsolescence versus avoidance of the lifetime composite risk of bleeding and thromboembolism and the nuisance of ongoing anticoagulation management. Both valve types can develop complications, which, although rare, can result in reoperation, stroke, or death.

The U.S. Food and Drug Administration (FDA) approved a randomized trial to test the safety of less aggressive anti-clotting treatment than the American Heart Association/American College of Cardiology guidelines currently recommend, in patients implanted with a newer generation On-X heart valve. “This is a bileaflet mechanical valve approved by the FDA, which is designed to function with less anticoagulation, or in some cases, antiplatelet therapy only,” explains John Puskas, M.D., professor of cardiothoracic surgery at the Icahn School of Medicine at Mount Sinai, and chairman of the department of cardiothoracic surgery, Mount Sinai Beth Israel, New York, N.Y.

In this first phase of the three-phase Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT), conducted under an FDA investigational device exemption, 375 aortic valve replacement patients with elevated risk factors for clotting were randomized into control (190) and test (185) groups from September 2006 to December 2009 at 33 U.S. centers. Patients in the control group received standard treatment of warfarin to maintain a target range of the International Normalized Ratio (INR) of 2.0—3.0. Patients in the treatment group received low-dose warfarin, targeting an INR of 1.5—2.0, after an initial 90 postoperative days of standard therapy. All patients received 81 mg aspirin daily.

The patients were followed up by in-person visits at three months, six months and one year after surgery and then annually for between five and eight postoperative years to accrue the necessary 800 patient-years of follow-up mandated by the FDA. During these visits, electrocardiography or echocardiography was performed as required by the protocol and as clinically indicated. All patients maintained with warfarin therapy were followed up using weekly home INR testing through a central telephone or online database.

“The results show that anticoagulation may be safely reduced in patients following aortic valve replacement with this approved bileaflet mechanical prosthesis,” Puskas said. “INR can be safely maintained between 1.5 and 2.0. With low-dose aspirin, this resulted in a significantly lower risk of bleeding, without a significant increase in thromboembolism. In high-risk recipients of On-X valves, the INR should be assiduously kept above 1.5 to maximize the safety and effectiveness of this therapeutic change,” he concludes.

The investigators caution that results from the present trial should not be extrapolated to other prostheses, mechanical mitral valve replacements or patients undergoing double aortic valve/mitral valve replacement. The present standard of care for all mechanical AVR patients outside the PROACT study remains conventional anticoagulation, as indicated by the AHA/ACC guidelines.

Two further phases of PROACT are planned. The second will be used to compare current anticoagulant therapy versus aspirin and/or clopidogrel only in selected lower risk patients requiring aortic valve replacement. The third will compare standard anticoagulation therapy versus INR goal of 2.0 to 2.5 in patients requiring mitral valve replacement.

For more information: www.jtcvsonline.org

Related Content

Pfizer Announces Positive Topline Results from Phase 3 ATTR-ACT Study
News | Pharmaceuticals | April 06, 2018
Pfizer Inc. announced that the Tafamidis Phase 3 Transthyretin Cardiomyopathy (ATTR-ACT) study met its primary endpoint...
Humanetics Presents Data on Drug to Protect Cardiac Cells From Space-Like Radiation

Photo from NASA

News | Pharmaceuticals | February 01, 2018
February 1, 2018 –Humanetics Corporation (Humanetics) has recently completed two research studies funded by the Natio
Xarelto Significantly Reduces Major Cardioavascular Events in Stable CAD and PAD Patients
News | Pharmaceuticals | October 18, 2017
October 18, 2017 — Results from the pivotal Phase 3 COMPASS study found that the...
News | Pharmaceuticals | October 04, 2017
October 4, 2017 — MyoKardia Inc.
News | Pharmaceuticals | September 12, 2017
September 12, 2017 — Inclisiran lowers low-density lipoprotein (LDL, or “bad”) cholesterol for up to one year in pati
Merck Announces Results of REVEAL Outcomes Study of Anacetrapib
News | Pharmaceuticals | September 11, 2017
Merck and researchers in the Clinical Trial Service Unit at the University of Oxford announced the publication and...
Statins Associated With Improved Heart Structure and Function
News | Pharmaceuticals | May 26, 2017
Statins are associated with improved heart structure and function, according to research presented at EuroCMR 2017, May...
Feature | Pharmaceuticals | May 16, 2017
May 16, 2017 – Results of a groundbreaking clinical trial demonstrate the effectiveness of a novel, fast-acting nasal
Prescribing Patterns Change Following Direct Marketing Restrictions
News | Pharmaceuticals | May 05, 2017
A study of how policies restricting pharmaceutical promotion to physicians affect medication prescribing found...
EBBINGHAUS study, evolocumab, repatha, statin therapy, cognitive issues, ACC.17 study
News | Pharmaceuticals | April 03, 2017
There is no evidence that adding a new cholesterol-lowering drug to treatment with a statin causes memory loss or other...
Overlay Init