Anticoagulation in chronic nonvalvular atrial fibrillation: a critical appraisal and meta-analysis

Can J Cardiol. 1997 Sep;13(9):811-5.


Objective: To assess the outcomes associated with warfarin treatment of patients with chronic nonvalvular atrial fibrillation (CNVAF) for prevention of primary stroke.

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

Study selection: Five published randomized controlled trials concerning primary stroke prevention.

Data extraction: 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.

Data synthesis: 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / prevention & control*
  • Humans
  • Incidence
  • Outcome Assessment, Health Care
  • Research Design
  • Risk Factors
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Warfarin