Reducing Stroke Rates in Patients With Atrial Fibrillation

S trokes related to atrial fibrillation tend to be large, life- threatening, and disabling.Multiple factors have synergistically led, over the past 20 years, to an impressive reduction in atrial fibrillation-related stroke rates.Comparisons of these rates between studies are estimates because definitions of stroke and primary end points among trials differ.However, patients assigned to placebo or usual therapy from clinical trials conducted in the late 1980s and early 1990s found approximate rates for patients with the equivalent of a CHADS2 score (an acronym for congestive heart failure, hypertension, age Ն75, diabetes mellitus, and prior stroke or transient ischemic attack) of 2 of Ϸ6% to 8%.1,2 A CHADS2 score of 2 is the approximate stroke risk of patients entered in current trials, including A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalization or Death From Any Cause in Patients With Atrial Fibrillation/Atrial Flutter (ATHENA).3 Anticoagulation with vitamin k antagonists has been the major contributor to the declining event rates; compared with placebo, vitamin k antagonists have reduced rates from 67% to 86% in completed trials, which translates into stroke rates of Ϸ1.4%/y.4,5 Novel anticoagulants designed to overcome the limitations of warfarin have been evaluated recently and have attained rates comparable to or slightly lower than coumadin, but at the price of either an increased incidence in major bleeding 6 or liver toxicity.7,8 In a recent trial of elderly subjects with atrial fibrillation, warfarin was superior to aspirin, 9 and in patients at intermediate to high risk for stroke, warfarin was superior to the combination of aspirin and clopidogrel with similar bleed rates.10 Thus, for time being, warfarin remains the only effective orally administered anticoagulant available.