Effectiveness and safety of direct oral anticoagulation vs. warfarin in frail patients with atrial fibrillation

Mette Søgaard*, Anne Gulbech Ording, Flemming Skjøth, Torben Bjerregaard Larsen, Peter Brønnum Nielsen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)


Aims: Although frail patients with atrial fibrillation (AF) carry a high risk of stroke and treatment-related bleeding complications, evidence for the safety and effectiveness of anticoagulation remains sparse. This study investigated the effectiveness and safety of direct oral anticoagulant (DOAC) vs. warfarin in frail AF patients.

Methods and results: Nationwide registry-based cohort study including 32 048 anticoagulation naïve frail patients (median age 80 years, 53% female) with incident AF during 2012-20. Frailty was assessed using the hospital frailty risk score. To address baseline confounding, we applied inverse probability of treatment weighting (IPTW) and marginal structural models with weighted pooled regression to compute weighted hazard ratios (wHRs) and risk differences for thromboembolism and major bleeding comparing specific DOAC doses with warfarin. After AF diagnosis, 6747 (21.1%) initiated warfarin, 17 076 (50.3%) initiated standard-dose DOAC, and 9179 (28.6%) initiated reduced-dose DOAC. Comparative effectiveness analyses in the IPTW pseudo-populations revealed similar thromboembolism risk between standard-dose DOAC and warfarin [wHR 0.95, 95% confidence interval (CI) 0.80-1.13] and between reduced-dose DOAC and warfarin (wHR 0.97, 95% CI 0.77-1.23). The 1-year thromboembolic event-free survival difference was -0.2% for DOAC, regardless of dosing, vs. warfarin. Major bleeding risk was significantly lower with standard-dose DOAC (wHR 0.69, 95% CI 0.59-0.87) and reduced-dose DOAC (wHR 0.67, 95% CI 0.55-0.81) vs. warfarin. The 1-year bleeding risk difference with DOAC ranged from -1.3% to -3.0%.

Conclusion: Our findings indicate comparable thromboembolism risk and significantly lower bleeding risk with both standard and reduced DOAC regimens compared with warfarin in frail AF patients in routine care.
Original languageEnglish
Article numberpvad091
JournalEuropean Heart Journal - Cardiovascular Pharmacotherapy
Issue number2
Pages (from-to)137-146
Number of pages10
Publication statusPublished - Mar 2024

Bibliographical note

© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.


  • Aged
  • Aged, 80 and over
  • Anticoagulants
  • Atrial Fibrillation/complications
  • Cohort Studies
  • Female
  • Frail Elderly
  • Frailty/diagnosis
  • Hemorrhage/chemically induced
  • Humans
  • Male
  • Thromboembolism/diagnosis
  • Warfarin
  • Atrial fibrillation
  • Anticoagulation
  • Frailty
  • Haemorrhage
  • Thromboembolism


Dive into the research topics of 'Effectiveness and safety of direct oral anticoagulation vs. warfarin in frail patients with atrial fibrillation'. Together they form a unique fingerprint.

Cite this