ANTICOAGULATION IN CHRONIC NONVALVULAR ATRIAL-FIBRILLATION - A CRITICAL-APPRAISAL AND METAANALYSIS

OBJECTIVE: To assess the outcomes associated with warfarin treatment o f patients with chronic nonvalvular atrial fibrillation (CNVAF) for pr evention of primary stroke. DATA SOURCES: MEDLINE was searched for lit erature published from 1987 to August 1996. Search terms used were 'at rial fibrillation' and 'anticoagulants'. STUDY SELECTION: Five publish ed randomized controlled trials concerning primary stroke prevention. DATA EXTRACTION: Data were pooled across trials to estimate the magnit ude of the effect for each of nine reported endpoints. The annual prob ability of occurrence of each outcome was calculated, including standa rd errors and Mantel-Haenszel significance tests with 95% CIs. DATA SY NTHESIS: In view of the lack of blinded assessment and documented low inter-rater reliability of soft neurological end-points, the analysis was limited to the relatively objective end-points of major strokes, f atal strokes, major bleeding and fatal bleeding. Warfarin did not redu ce the incidence of fatal strokes to a statistically significant exten t, nor was incidence of fatal bleeding increased significantly. Warfar in reduced the absolute annual incidence of major strokes in patients with CNVAF by 0.89%, while at the same time it increased the absolute annual risk of major bleeding incidents by 1.8%. Though small, these d ifferences were statistically significant. CONCLUSIONS: On balance, th e margin between expected benefit and harm for warfarin prophylaxis in patients with CNVAF is uncomfortably thin. These results and conclusi ons differ from those of a previously published meta-analysis of these same studies.