The SPORTIF V (Stroke Prevention using an ORal Direct Thrombin Inhibitor in Patients with Atrial Fibrillation) trial, the largest stroke prevention trial ever conducted in patients with atrial fibrillation, was designed to evaluate whether fixed oral-dose ximelagatran (36 mg twice daily) is as effective as well-controlled warfarin (dose-adjusted to a standard level of anticoagulation intensity, INR 2-3) in preventing all strokes and systemic embolic events. Results showed that patients treated with ximelagatran (n=1,960) had a 1.6 percent per year chance of having a stroke or systemic embolic event (51 events), compared to a 1.2 percent chance for 1,962 patients treated with warfarin (37 events). Those receiving ximelagatran experienced a 4.2 percent per year rate of death, stroke, systemic embolic events and acute myocardial infarction (110 events), compared to 4.4 percent (121 events) for patients on warfarin. The SPORTIF V study was double-blind, involving 3,922 patients in the U.S and Canada who also had one or more stroke risk factors in addition to AF (age 75 or older, prior stroke or blood clot, a history of congestive heart failure or hypertension or certain combinations of advanced age and diabetes or coronary artery disease). The research was sponsored by AstraZeneca PLC, which is developing ximelagatran under the trade name EXANTA. Ximelagatran is currently approved for short-term use in some European countries, but it has not been approved in the United States.
"The SPORTIF data indicate a solid clinical benefit to ximelagatran, and publication of the study in JAMA adds to the body of evidence about the potential of this therapy," said Jonathan L. Halperin, M.D., Professor of Medicine and Director of Cardiology Clinical Services at the Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Center for Cardiovascular Health at The Mount Sinai Medical Center. "Clinicians see a major unmet medical need among patients with atrial fibrillation, who would benefit from access to new treatment options. The medical community will continue to work to safely bring to market new therapies that protect those at risk of stroke, without the drawbacks of existing therapies."
SPORTIF V was one of two Phase III clinical trials involving 7,329 patients. SPORTIF III, an open-label trial previously conducted outside North America, found that patients taking ximelagatran experienced no more strokes or bleeding than those on well-controlled warfarin.
In SPORTIF V, 63 patients receiving ximelagatran experienced major bleeding events compared to 84 patients in the warfarin arm (p=0.155). Six percent of patients treated with ximelagatran experienced an increase of a liver enzyme called ALT to greater than three times the upper limit of normal, compared to 0.8 percent of patients in the warfarin group. Although nearly all enzyme changes occurred within the first six months of treatment with ximelagatran and decreased either with or without drug discontinuation, a few patients developed more severe liver reactions.
About Atrial Fibrillation
Atrial Fibrillation (AF) is a common irregular heartbeat that occurs when the two small upper chambers of the heart (known as the atria) beat rapidly and unpredictably, which sometimes allows blood to pool and clot. If a section of the blood clot breaks off and travels to an artery in the brain, a stroke may result. AF affects more than two million Americans, and this number is expected to more than double by 2050. Approximately 15 percent of all strokes occur in people with AF. Age, high blood pressure, diabetes and congestive heart failure further increase the risk of stroke in patients with AF. Patients with AF also tend to have more disabling strokes compared to those without AF. In fact, among patients who suffer a stroke, people with AF are 70 percent more likely to die than people without AF.
Stroke risk in patients with AF can be reduced by more than 60 percent using oral anticoagulant therapy such as warfarin. However, many eligible patients are not receiving oral anticoagulant therapy. Warfarin interacts with many foods and medications, requiring frequent blood test monitoring and dose adjustments to prevent excessive bleeding or inadequate anticoagulation.
Cardiovascular Research At Mount Sinai
The Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée and Henry R. Kravis Center for Cardiovascular Health at The Mount Sinai Medical Center are preeminent resources for the study and treatment of heart and blood vessel diseases. Committed to finding new and improved methods of diagnosis, treatment and prevention, they comprise a multidisciplinary effort that brings together the extraordinary expertise of Mount Sinai School of Medicine and The Mount Sinai Hospital in cardiology, cardiovascular surgery, medical education, research and community service, with state-of-the-art facilities for patient care, advanced laboratories for scientific research and leading programs for postgraduate education of clinician-scientists.
Journal
JAMA