Anticoagulation in chronic nonvalvular atrial fibrillation: a critical appraisal and meta-analysis.
OBJECTIVE
To assess the outcomes associated with warfarin treatment of patients with chronic nonvalvular atrial fibrillation (CNVAF) for prevention of primary stroke.


METHODS
MEDLINE was searched for literature published from 1987 to August 1996. Search terms used were 'atrial fibrillation' and 'anticoagulants'.


METHODS
Five published randomized controlled trials concerning primary stroke prevention.


METHODS
Data were pooled across trials to estimate the magnitude of the effect for each of nine reported end-points. The annual probability of occurrence of each outcome was calculated, including standard errors and Mantel-Haenszel significance tests with 95% CIs.


RESULTS
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, fatal strokes, major bleeding and fatal bleeding. Warfarin did not reduce the incidence of fatal strokes to a statistically significant extent, nor was incidence of fatal bleeding increased significantly. Warfarin 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 differences were statistically significant.


CONCLUSIONS
On balance, the margin between expected benefit and harm for warfarin prophylaxis in patients with CNVAF is uncomfortably thin. These results and conclusions differ from those of a previously published meta-analysis of these same studies.
Green
C J
CJ
British Columbia Office of Health Technology Assessment, University of British Columbia, Vancouver. cjgreen@unixg.ubc.ca
Hadorn
D C
DC
Bassett
K
K
Kazanjian
A
A
D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D017063:Outcome Assessment, Health Care; D012107:Research Design; D012307:Risk Factors; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin