Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis

Arch Intern Med. 2012 Apr 23;172(8):623-31; discussion 631-3. doi: 10.1001/archinternmed.2012.121. Epub 2012 Mar 26.


Background: Although several new antithrombotic agents have been developed for stroke prevention in patients with nonvalvular atrial fibrillation (AF), many patients will continue to be treated with warfarin worldwide. We performed a meta-analysis of safety and efficacy outcomes in patients with AF treated with warfarin for stroke prevention in large contemporary randomized controlled trials (RCTs).

Methods: We searched the MEDLINE, EMBASE, and Cochrane databases for relevant studies; RCTs comparing warfarin with an alternative thromboprophylaxis strategy with at least 400 patients in the warfarin arm and reporting stroke as an efficacy outcome were included.

Results: Eight RCTs with 55,789 patient-years of warfarin therapy follow-up were included. Overall time spent in the therapeutic range was 55% to 68%. The annual incidence of stroke or systemic embolism in patients with AF taking warfarin was estimated to be 1.66% (95% CI, 1.41%-1.91%). Major bleeding rates varied from 1.40% to 3.40% per year across the studies. The risk of stroke per year was significantly higher in elderly patients (2.27%), female patients (2.12%), patients with a history of stroke (2.64%), and patients reporting no previous exposure to vitamin K antagonists (1.96%). There was a significant increase in the annual incidence of stroke with progressively increasing CHADS(2) (congestive heart failure, hypertension, age, diabetes, and prior stroke) scores.

Conclusions: Current use of warfarin as a stroke prevention agent in patients with AF is associated with a low rate of residual stroke or systemic embolism estimated to be 1.66% per year. Compared with a previous meta-analysis, there has been significant improvement in the proportion of time spent in therapeutic anticoagulation, with a resultant decline in observed stroke rates.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Aspirin / therapeutic use
  • Atrial Fibrillation / complications*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / etiology
  • Azetidines / therapeutic use
  • Benzylamines / therapeutic use
  • Brain Ischemia / prevention & control
  • Clopidogrel
  • Female
  • Humans
  • Incidence
  • Male
  • Oligosaccharides / therapeutic use
  • Primary Prevention / methods
  • Pyrazoles / therapeutic use
  • Pyridones / therapeutic use
  • Randomized Controlled Trials as Topic
  • Stroke / epidemiology*
  • Stroke / etiology
  • Stroke / prevention & control*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Treatment Outcome
  • United States / epidemiology
  • Warfarin / administration & dosage
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Azetidines
  • Benzylamines
  • Oligosaccharides
  • Pyrazoles
  • Pyridones
  • apixaban
  • ximelagatran
  • Warfarin
  • idraparinux
  • Clopidogrel
  • Ticlopidine
  • Aspirin