Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation according to the drug labelling and the EHRA Practical Guide

Int J Cardiol. 2021 Apr 1;328:97-103. doi: 10.1016/j.ijcard.2020.11.062. Epub 2020 Dec 3.


Background: This study aimed to evaluate the prevalence of potential drug-drug interactions (DDIs) and the appropriateness of direct oral anticoagulant (DOAC) dosing according to both the Summary of Product Characteristics (SmPC) and the European Heart Rhythm Association (EHRA) Practical Guide in a 'real-world' sample of non-valvular atrial fibrillation (NVAF) patients.

Methods and results: Data of a cross-sectional observational study in a primary care sample of 654 long-term DOAC users were used for this sub-analysis. A total of 262 potential DDIs were identified in 220 patients (33.6%). Pharmacodynamic DDIs were present in 163 patients (24.9%) and pharmacokinetic DDIs in 82 patients (12.5%). One-third of patients (33.8%) received reduced DOAC dose. According to the dosing recommendations in the SmPC, 81.7% of DOACs were dosed appropriately. According to the EHRA recommendations, 76.6% of DOACs were dosed appropriately. Dosing recommendations were consistent for 90.7% of patients, with both the SmPC and EHRA Practical Guide considering DOACs dosed appropriately in 74.5% of patients, overdosed in 7.8%, underdosed in 7.6% and contraindicated in 0.8%. However, for the remaining 9.3% dosing recommendations differed between SmPC and EHRA.

Conclusions: This 'real-world' analysis of DOAC dosing demonstrated that in about one-third of NVAF patients potential DDIs were present. In 18.3% and 23.4% of patients, DOACs were dosed inappropriately according to the SmPC and EHRA Practical Guide respectively. In almost 10% of the study population dosing advice was inconsistent between both references. More research is needed to ensure appropriate DOAC dosing in this 'grey zone' population.

Keywords: Atrial fibrillation; Direct oral anticoagulants; Inappropriate prescribing; Pharmacology.

Publication types

  • Observational Study

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Cross-Sectional Studies
  • Drug Labeling
  • Humans
  • Stroke* / drug therapy


  • Anticoagulants