title: Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Ohio, USA.
authors.forename: Shikhar
authors.initials: S
authors.lastname: Agarwal
authors.forename: Rory
authors.initials: R
authors.lastname: Hachamovitch
authors.forename: Venu
authors.initials: V
authors.lastname: Menon
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy* / Q000209:etiology; D001384:Azetidines / Q000627:therapeutic use; D001596:Benzylamines / Q000627:therapeutic use; D002545:Brain Ischemia / Q000517:prevention & control; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009844:Oligosaccharides / Q000627:therapeutic use; D011322:Primary Prevention / Q000379:methods; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D009844:Oligosaccharides; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; C426686:ximelagatran; D014859:Warfarin; C479958:idraparinux; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin