Lessons from warfarin trials in atrial fibrillation: Missing the window of opportunity

Abstract

Between September 1985 and June 1987, five clinical trials were initiated to evaluate the use of warfarin to prevent stroke in patients with nonrheumatic, non-valvular atrial fibrillation. They were similar in terms of study population and primary outcome, but differed in their International Normalized Ratio (INR) goals. The first three trials, all terminated early between January 1989 and November 1990, reported marked reductions in embolic complications with warfarin. As a consequence, the remaining trials were terminated ahead of schedule, primarily for ethical reasons. Publication of results from similar trials can influence ongoing trials, potentially closing the ethical window of opportunity by withholding proven beneficial treatment. © 2006 Springer-Verlag New York.