The goal of this study was to analyze the impact of dabigatran plasma concentrations,
patient demographics, and aspirin (ASA) use on frequencies of ischemic strokes/systemic
emboli and major bleeds in atrial fibrillation patients.
The efficacy and safety of dabigatran etexilate were demonstrated in the RE-LY (Randomized
Evaluation of Long-Term Anticoagulation Therapy) trial, but a therapeutic concentration
range has not been defined.
In a pre-specified analysis of RE-LY, plasma concentrations of dabigatran were determined
in patients treated with dabigatran etexilate 110 mg twice daily (bid) or 150 mg bid
and correlated with the clinical outcomes of ischemic stroke/systemic embolism and
major bleeding using univariate and multivariate logistic regression and Cox regression
models. Patient demographics and ASA use were assessed descriptively and as covariates.
Plasma concentrations were obtained from 9,183 patients, with 112 ischemic strokes/systemic
emboli (1.3%) and 323 major bleeds (3.8%) recorded. Dabigatran levels were dependent
on renal function, age, weight, and female sex, but not ethnicity, geographic region,
ASA use, or clopidogrel use. A multiple logistic regression model (c-statistic 0.657,
95% confidence interval [CI]: 0.61 to 0.71) showed that the risk of ischemic events
was inversely related to trough dabigatran concentrations (p = 0.045), with age and
previous stroke (both p < 0.0001) as significant covariates. Multiple logistic regression
(c-statistic 0.715, 95% CI: 0.69 to 0.74) showed major bleeding risk increased with
dabigatran exposure (p < 0.0001), age (p < 0.0001), ASA use (p < 0.0003), and diabetes
(p = 0.018) as significant covariates.
Ischemic stroke and bleeding outcomes were correlated with dabigatran plasma concentrations.
Age was the most important covariate. Individual benefit-risk might be improved by
tailoring dabigatran dose after considering selected patient characteristics. (Randomized
Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600).
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier
Inc. All rights reserved.