Factors affecting serum concentration of dabigatran in Asian patients with non-valvular atrial fibrillation
Journal Volume
118
Journal Issue
7
Pages
1154-1160
Date Issued
2019
Abstract
Background/purpose: Dabigatran is effective in preventing ischemic stroke and systemic embolism in patients with atrial fibrillation. Although the therapeutic window for dabigatran is wide, its pharmacokinetic properties can differ between specific populations. This study aimed to establish a real-life plasma dabigatran concentration database and investigate potential factors affecting this concentration in Asians. Methods: Patients under dabigatran therapy were recruited. Plasma dabigatran concentration was determined in trough and peak blood samples by using ultra-high performance liquid chromatography with tandem mass spectrometry analysis. Factors affecting the dabigatran concentration were investigated. Results: A total of 46 patients (33 male, 71.7%) were prospectively enrolled. Most of them were receiving a low dose regimen (110 mg twice daily, n = 38, 82.6%). The trough and peak concentrations were significantly correlated (p < 0.001), and the trough concentration was higher in patients aged ?75 years, body weight ?60 kg, creatinine clearance (CrCl) ?50 mL/min, CHA2DS2-VASc score >3 points, and HAS-BLED score ?3 points. Multiple linear regression analysis identified body weight and serum creatinine as key factors predicting trough concentration (p = 0.003 and 0.005, respectively). Importantly, drug adherence was the only independent factor associated with low trough concentration, defined as the lowest 20th percentile in our study cohort (n = 10, hazard ratio = 9.07; 95% CI, 1.12 to 73.22; p = 0.004). Conclusion: Dabigatran monitoring may be considered for patients at risk of overexposure, especially those with low body weight and renal insufficiency, and also for detecting those with extremely low drug concentration. ? 2018
SDGs
Other Subjects
creatinine; dabigatran; dabigatran etexilate; antithrombin; creatinine; dabigatran; age; aged; Article; Asian; atrial fibrillation; bleeding; CHA2DS2-VASc score; clinical article; clinical outcome; cohort analysis; creatinine blood level; creatinine clearance; drug blood level; drug exposure; drug megadose; drug monitoring; drug withdrawal; female; HAS BLED score; human; kidney failure; liquid chromatography-mass spectrometry; low drug dose; male; maximum plasma concentration; medication compliance; patient compliance; prospective study; scoring system; subdural hematoma; thrombosis; trough concentration; atrial fibrillation; blood; cerebrovascular accident; middle aged; procedures; risk assessment; risk factor; severity of illness index; statistical model; Taiwan; very elderly; Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Creatinine; Dabigatran; Drug Monitoring; Female; Humans; Linear Models; Male; Medication Adherence; Middle Aged; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Taiwan
Type
journal article