Abstract
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. 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. 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. www.clinicaltrials.gov number, NCT00262600.
Highlights
Applying data from clinical trials to everyday practice is a significant challenge in the current age of evidence-based medicine
For 18040 patients randomized in Randomized Evaluation of Long-Term Anticoagulation Therapy (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 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%
Summary
Applying data from clinical trials to everyday practice is a significant challenge in the current age of evidence-based medicine. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial compared warfarin with dabigatran in patients with atrial fibrillation at increased risk for stroke, and found lower risk of stroke or systemic embolism and a comparable risk of major bleeding with dabigatran 150mg twice daily; the risk of gastrointestinal bleeding was significantly higher with dabigatran 150mg [10]. We used data from the RE-LY trial to create models predicting individual patients’ risk for stroke or systemic embolism and for major bleeding with alternative doses of dabigatran as compared with warfarin, with the hope these models would provide a means for translating the results of RE-LY to clinical practice [2]. 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
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