Individual Treatment Effect Estimation of 2 Doses of Dabigatran on Stroke and Major Bleeding in Atrial Fibrillation: Results from the RE-LY Trial.

BACKGROUND: We aimed to estimate absolute benefit and harm from treatment with dabigatran in individual patients with atrial fibrillation, and to select the optimal dose for each individual.

METHODS: We derived and validated a prediction model for ischemic stroke/ systemic embolism (SE) and major bleeding in patients with atrial fibrillation from the 3 treatment arms of the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial (n=11,955 in derivation cohort, n=6,158 in validation cohort). Readily available patient characteristics were included in Fine &#x0026 Gray competing risk models (sex, age, smoking, antiplatelet drugs, prior vascular disease, diabetes, blood pressure, eGFR, and hemoglobin). Five-year risks for ischemic stroke/SE and major bleeding were estimated without anticoagulation therapy, and compared with high and low dose dabigatran.

RESULTS: Model calibration was good, and discrimination was adequate with a c-statistic of 0.65 (95%CI 0.62-0.70) for ischemic stroke/SE and 0.69 (95%CI 0.66-0.71) for major bleeding. The 5-year absolute risk reduction (ARR) for ischemic stroke/SE with dabigatran 150 mg twice daily ranged from <10% in 20% of patients to >25% in 7% of patients, and the 5-year absolute risk increase (ARI) for major bleeding ranged from <5% in 53% of patients to 15-20% in 1% of patients. Comparing high-dose to low-dose dabigatran, the net benefit (ARR - ARI) was positive for 46% of patients.

CONCLUSIONS: The absolute treatment benefits and harms of dabigatran in atrial fibrillation can be estimated based on readily available patient characteristics. Such treatment effect estimations can be used for shared decision-making before starting dabigatran treatment, and to determine the optimal dose.

CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique identifier: NCT00262600.