Related Experiment Video
Updated: Jul 22, 2026
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Anticoagulation in chronic nonvalvular atrial fibrillation: a critical appraisal and meta-analysis
C J Green1, D C Hadorn, K Bassett
1British Columbia Office of Health Technology Assessment, University of British Columbia, Vancouver. cjgreen@unixg.ubc.ca
Insights
Warfarin treatment for chronic nonvalvular atrial fibrillation (CNVAF) shows a small benefit in preventing major strokes but increases bleeding risk. The balance between benefits and harms is narrow, requiring careful consideration for stroke prevention.
Area of Science:
- Cardiology
- Neurology
- Pharmacology
Background:
- Chronic nonvalvular atrial fibrillation (CNVAF) increases stroke risk.
- Warfarin is used for stroke prevention in CNVAF patients.
- Previous studies have yielded varying conclusions on warfarin's efficacy.
Purpose of the Study:
- To assess warfarin's outcomes for primary stroke prevention in CNVAF patients.
- To analyze the balance between warfarin's benefits (stroke reduction) and harms (bleeding).
Main Methods:
- Systematic literature search of MEDLINE (1987-1996) for anticoagulants and atrial fibrillation.
- Inclusion of five randomized controlled trials focused on primary stroke prevention.
- Pooled data analysis of objective endpoints: major strokes, fatal strokes, major bleeding, and fatal bleeding.
Main Results:
- Warfarin did not significantly reduce fatal strokes or significantly increase fatal bleeding.
- Warfarin reduced the absolute annual incidence of major strokes by 0.89% in CNVAF patients.
- Warfarin significantly increased the absolute annual risk of major bleeding by 1.8%.
Conclusions:
- The margin between warfarin's expected benefits and harms for CNVAF stroke prevention is narrow.
- Findings contrast with previous meta-analyses of the same studies.
- Clinical decisions regarding warfarin in CNVAF require careful risk-benefit assessment.
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.
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:29Venous Thrombosis III: Interprofessional Care