In 9,183 atrial fibrillation patients, ischemic events were inversely related to trough dabigatran concentrations (p=0.045), while major bleeding risk increased with dabigatran exposure (p<0.0001).
RCT (n=9,183)
Yes
Effect estimate: c-statistic 0.657 (95% CI 0.61-0.71)
p-value: p=0.045
OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. 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 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. 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. (Randomized Evaluation of Long Term Anticoagulant Therapy RE-LY With Dabigatran Etexilate; NCT00262600).
“The paper by Reilly et al. suggested that up to 20% of patients using the 110 and 150 mg twice daily dosing will fall outside of the optimal concentration range of 35 to 300 ng/ml. Recently unsealed court documents reveal internal pharmaceutical correspondence that suppressed important data regarding dabigatran therapy for patients with atrial fibrillation.”
Reilly et al. (Fri,) conducted a rct in Atrial fibrillation (n=9,183). Dabigatran etexilate was evaluated on Ischemic stroke/systemic embolism and major bleeding (c-statistic 0.657, 95% CI 0.61-0.71, p=0.045). In 9,183 atrial fibrillation patients, ischemic events were inversely related to trough dabigatran concentrations (p=0.045), while major bleeding risk increased with dabigatran exposure (p<0.0001).