Risks for Stroke, Bleeding, and Death in Patients With Atrial Fibrillation Receiving Dabigatran or Warfarin in Relation to the CHADS₂ Score: A Subgroup Analysis of the RE-LY Trial

BACKGROUND: CHADS(2) is a simple, validated risk score for predicting the risk for stroke in patients with atrial fibrillation not treated with anticoagulants. There are sparse data on the risk for thrombotic and bleeding complications according to the CHADS(2) score in patients receiving anticoagulant therapy. OBJECTIVE: To evaluate the prognostic importance of CHADS(2) risk score in patients with atrial fibrillation receiving oral anticoagulants, including the vitamin K antagonist warfarin and the direct thrombin inhibitor dabigatran. DESIGN: Subgroup analysis of a randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00262600) SETTING: Multinational study setting. PATIENTS: 18 112 patients with atrial fibrillation who were receiving oral anticoagulants. MEASUREMENTS: Baseline CHADS(2) score, which assigns 1 point each for congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and 2 points for stroke. RESULTS: Distribution of CHADS(2) scores were as follows: 0 to 1-5775 patients; 2-6455 patients; and 3 to 6-5882 patients. Annual rates of the primary outcome of stroke or systemic embolism among all participants were 0.93% in patients with a CHADS(2) score of 0 to 1, 1.22% in those with a score of 2, and 2.24% in those with a score of 3 to 6. Annual rates of other outcomes among all participants with CHADS(2) scores of 0 to 1, 2, and 3 to 6, respectively, were the following: major bleeding, 2.26%, 3.11%, and 4.42%; intracranial bleeding, 0.31%, 0.40%, and 0.61%; and vascular mortality, 1.35%, 2.39%, and 3.68% (P < 0.001 for all comparisons). Rates of stroke or systemic embolism, major and intracranial bleeding, and vascular and total mortality each increased in the warfarin and dabigatran groups as CHADS(2) score increased. The rates of stroke or systemic embolism with dabigatran, 150 mg twice daily, and of intracranial bleeding with dabigatran, 150 mg or 110 mg twice daily, were lower than those with warfarin; there was no significant heterogeneity in subgroups defined by CHADS(2) scores. LIMITATION: These analyses were not prespecified and should be deemed exploratory. CONCLUSION: Higher CHADS(2) scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants. PRIMARY FUNDING SOURCE: Boehringer Ingelheim.