The Effect of Dabigatran Plasma Concentrations and Patient Characteristics on the Frequency of Ischemic Stroke and Major Bleeding in Atrial Fibrillation Patients in the RE-LY Trial.
J Am Coll Cardiol. 2013 Sep 26;
Authors: Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, Ezekowitz MD, Nehmiz G, Wang S, Wallentin L
OBJECTIVES: Analyze the impact of dabigatran plasma concentrations, patient demographics and ASA use on frequencies of ischemic strokes/systemic emboli and major bleeds in atrial fibrillation patients .
BACKGROUND: The efficacy and safety of dabigatran etexilate were demonstrated in the RE-LY trial, but a therapeutic concentration range has not been defined.
METHODS: In a prespecified analysis of RE-LY, plasma concentrations of dabigatran were determined in patients treated with dabigatran etexilate 110 mg 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.
RESULTS: 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 gender but not ethnicity, geographic region, ASA or clopidogrel use. A multiple logistic regression model (c-statistic 0.657, 95% CI: 0.61-0.71) 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: 0.69-0.74) showed major bleeding risk increased with dabigatran exposure (p<0.0001), age (p< 0.0001), aspirin use (p< 0.0003) and diabetes (p= 0.018) as significant covariates.
CONCLUSIONS: 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.
PMID: 24076487 [PubMed - as supplied by publisher]