Dabigatran Concentration: Variability and Potential Bleeding Prediction In "Real-Life" Patients With Atrial Fibrillation

Basic Clin Pharmacol Toxicol. 2015 Nov;117(5):323-9. doi: 10.1111/bcpt.12417. Epub 2015 Jun 11.

Abstract

Routine laboratory monitoring is currently not recommended in patients receiving dabigatran despite its considerable variation in plasma concentration. However, in certain clinical situations, measurements of the dabigatran effect may be desirable. We aimed to assess the variability of dabigatran trough and peak concentration and explore the potential relationship between dabigatran concentration and adverse events. We included 44 patients with atrial fibrillation who started treatment with dabigatran 150 mg (D150) or 110 mg (D110) twice daily. They contributed 170 trough and peak blood samples that were collected 2-4 and 6-8 weeks after dabigatran initiation. Plasma dabigatran concentration was measured by LC-MS/MS and indirectly, by selected coagulation tests. D110 patients were older (74 ± 7 versus 68 ± 6 years), had lower creatinine clearance (68 ± 21 versus 92 ± 24 mL/min) and higher CHA2 DS2 -VASc score (3.1 ± 1.3 versus 2.3 ± 0.9) compared to D150 patients (all p < 0.05), but both had similar dabigatran concentrations in both trough and peak samples. Dabigatran concentrations varied less in trough than in peak samples (17.0 ± 13.6 versus 26.6 ± 19.2%, p = 0.02). During the 12-month follow-up, 4 patients on D150 and 6 on D110 suffered minor bleeding. There was no major bleeding or thromboembolic event. Patients with bleeding had significantly higher average trough dabigatran concentrations (93 ± 36 versus 72 ± 62 μg/L, p = 0.02) than patients without bleeding, while peak dabigatran values had no predictive value. Dabigatran dose selection according to the guidelines resulted in appropriate trough concentrations with acceptable repeatability. High trough concentrations may predispose patients to the risk of minor bleeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antithrombins / adverse effects*
  • Antithrombins / blood*
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Blood Coagulation / drug effects*
  • Blood Coagulation Tests
  • Chromatography, Liquid
  • Dabigatran / adverse effects*
  • Dabigatran / blood*
  • Drug Monitoring* / methods
  • Female
  • Hemorrhage / chemically induced*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Tandem Mass Spectrometry
  • Time Factors
  • Treatment Outcome

Substances

  • Antithrombins
  • Dabigatran