title: Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis.
abstract: OBJECTIVE
  To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin.
  
  
  METHODS
  A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed.
  
  
  RESULTS
  Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range.
  
  
  CONCLUSIONS
  Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.
authors.affiliation: MetaWorks Inc., 10 President's Landing, Third Floor, Medford, MA 02155, USA. Mreynolds@metaworksinc.com
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Reynolds
authors.forename: Kyle
authors.initials: K
authors.lastname: Fahrbach
authors.forename: Ole
authors.initials: O
authors.lastname: Hauch
authors.forename: Gail
authors.initials: G
authors.lastname: Wygant
authors.forename: Rhonda
authors.initials: R
authors.lastname: Estok
authors.forename: Catherine
authors.initials: C
authors.lastname: Cella
authors.forename: Luba
authors.initials: L
authors.lastname: Nalysnyk
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications*; D002545:Brain Ischemia / Q000209:etiology; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin