Individual Benefit and Harm of Dabigatran

Study Questions:

What is the absolute benefit and harm from treatment with dabigatran in individual patients with atrial fibrillation (AF) based on different doses?


Using data from the three arms of the RE-LY trial (dabigatran 150 mg, dabigatran 110 mg, warfarin), the authors derived and validated a prediction model for ischemic stroke/systemic embolism and major bleeding (n = 11,955 in derivation cohort, n = 6,158 in validation cohort). They used a Fine & Gray competing risk model to assess 5-year risks for thrombotic and bleeding outcomes using meta-analytic data comparing warfarin to no anticoagulation therapy.


The predictive model had good calibration and a discrimination c-statistic of 0.65 (95% confidence interval [CI], 0.62-0.70) for ischemic stroke and 0.69 (95% CI, 0.66-0.71) for major bleeding. The 5-year absolute risk reduction for ischemic stroke ranged from <10% to >25% when using dabigatran 150 mg based on specific patient factors. The 5-year absolute risk increase for major bleeding ranges from <5% to 15-20%. When comparing the absolute risk reduction and increase by risk groups, the net benefit was favorable for treatment with dabigatran 150 mg in 46% of patients.


The authors concluded that readily available clinical factors can be used to predict net clinical benefit of anticoagulation therapy in patients with AF.


The authors performed an interesting analysis to help personalize anticoagulation therapy in AF. Through the use of easily available clinical and demographic data (e.g., age, gender, ethnicity, antiplatelet use, prior stroke, prior bleeding, renal function), they are able to predict the 5-year risk of stroke and major bleeding for various treatment options (no anticoagulation, warfarin, dabigatran 110 mg, dabigatran 150 mg). Using various weighting of stroke:bleeding, the authors predict that between just fewer than half (1:1 weighting) to nearly all patients (2:1 weighting) are likely to get benefit from treatment with dabigatran 150 mg. This approach is quite useful for patient-provider shared decision making discussion. Caution should be taken before extrapolating findings from randomized clinical trials to unselected populations and in populations of patients treated with other direct oral anticoagulants. This model needs further validation and calibration in those patient cohorts.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Brain Ischemia, Embolism, Hemorrhage, Risk Factors, Secondary Prevention, Stroke, Thrombosis, Treatment Outcome, Warfarin

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