Warfarin anticoagulation and outcomes in patients with atrial fibrillation: A systematic review and metaanalysis

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, 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 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. (CHEST 2004; 126:1938–1945) Abbreviations: AF atrial fibrillation; CI confidence interval; INR international normalized ratio; OR odds ratio; RCT randomized clinical trial; TIA transient ischemic attack; UCS uncontrolled case series Learning Objectives: 1. To recognize that the INR below 2.0 was associated with a 5-fold increase in the risk of stroke in patients with nonvalvular atrial fibrillation. 2. To understand that an INR over 3 increased the risk of major bleeding 3-fold.