Personalizing the decision of dabigatran versus warfarin in atrial fibrillation: A secondary analysis of the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) trial

BACKGROUND: The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial demonstrated that higher-risk patients with atrial fibrillation had lower rates of stroke or systemic embolism and a similar rate of major bleeding, on average, when treated with dabigatran 150mg compared to warfarin. Since population-level averages may not apply to individual patients, estimating the heterogeneity of treatment effect can improve application of RE-LY in clinical practice. METHODS AND RESULTS: For 18040 patients randomized in RE-LY, we used patient-level data to develop multivariable models to predict the risk for stroke or systemic embolism and for major bleeding including all three treatment groups (dabigatran 110mg, dabigatran 150mg, and warfarin) over a median follow up of 2.0 years. The mean predicted absolute risk reduction (ARR) for stroke/systemic embolism with dabigatran 150mg compared to warfarin was 1.32% (range 11.6% lower to 3.30% higher risk). The mean predicted ARR for bleeding was 0.41% (range 8.93% lower to 63.4% higher risk). Patients with increased stroke/systemic embolism risk included those with prior stroke/TIA (OR 2.01), diabetics on warfarin (OR 2.00), and older patients on dabigatran 150mg (OR 1.68 for every 10-year increase). Major bleeding risk was higher in patients on aspirin (OR 1.25), with a history of diabetes (OR 1.34) or prior stroke/TIA (OR 1.22), those with heart failure on dabigatran 110mg (OR 1.52), older patients on either dabigatran 110mg or 150mg (OR 1.57 and 1.93, respectively, for each 10-year increase), and heavier patients on dabigatran 110mg or 150mg; patients in a region outside the United States and Canada and with better renal function had lower bleeding risk. CONCLUSIONS: There is substantial heterogeneity in the benefits and risks of dabigatran relative to warfarin among patients with atrial fibrillation. Using individualized estimates may enable shared decision making and facilitate more appropriate use of dabigatran; as such, it should be prospectively tested. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov number, NCT00262600.