Journal Article Ppublish 1 citation
PubMed: 42489390 DOI: 10.1016/j.jacadv.2026.102913
Outcomes With Warfarin in Atrial Fibrillation: Individual Patient Data Analysis From Four Randomized Trials.
JACC Adv 5(7):102913
Authors: Samer Al Said, Eugene Braunwald, Elaine M Hylek, Michael G Palazzolo, Andrea Bellavia, Elliott M Antman, Anthony P Carnicelli, John W Eikelboom, Christopher B Granger, Manesh R Patel, Lars Wallentin, Christian T Ruff, Robert P Giugliano
Affiliations
- TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
- Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
- Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
- Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
- Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
- Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
- TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND
Warfarin remains widely used for stroke prevention in atrial fibrillation (AF), particularly where access to direct oral anticoagulants (DOACs) is limited. Updated outcome data across clinical risk groups are needed.
OBJECTIVES
The objectives of the study were to identify predictors of adverse outcomes with warfarin, evaluate the TIMI-AF risk score, and assess the benefit of standard-dose (SD) DOACs vs warfarin across risk strata.
METHODS
Individual patient-level data from 58,634 patients (29,272 warfarin and 29,362 DOAC) enrolled in 4 pivotal randomized trials were analyzed. The net clinical outcome (NCO), defined as all-cause death, disabling or fatal stroke, or intracranial/fatal bleeding, was assessed using trial-stratified Cox models across key clinical subgroups and TIMI-AF risk score categories. Outcomes with SD-DOACs vs warfarin were compared across risk strata.
RESULTS
Older age (adjusted HR [aHR]: 1.55; 95% CI: 1.31-1.83), male sex (aHR: 1.30; 95% CI: 1.20-1.40), impaired kidney function (aHR: 2.21; 95% CI: 1.90-2.56), lower body mass index (aHR: 1.25; 95% CI: 1.15-1.36), vitamin K antagonist-naïve status (aHR: 1.17; 95% CI: 1.08-1.27), and nonparoxysmal AF (aHR: 1.31; 95% CI: 1.19-1.44) were independently associated with increased NCO risk (P < 0.001 for each). Annualized NCO rates were 3.5%, 7.6%, and 12.9% in low-, intermediate-, and high-risk TIMI-AF groups (P trend<0.001). SD-DOACs reduced NCO across all risk strata; however, absolute benefit with DOACs was modest in low-risk patients (0.3%; 95% CI: 0.1% to 0.6%).
CONCLUSIONS
Several predictors of poor warfarin outcomes were identified. Although SD-DOACs reduced NCO across the risk spectrum, patients with low TIMI-AF scores derived modest absolute benefit. In settings with limited DOAC access, warfarin may be a reasonable option for lower-risk patients.
MeSH
Stroke, Atrial Fibrillation, Data Analysis, Warfarin, Direct-Acting Oral Anticoagulants