Arrhythmias & electrophysiologyMeta-analysis
Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin
- Secondary analysis of the COMBINE-AF individual patient data (4 randomised trials)
- individual patient-level data
- subgroup analysis
- prespecified outcomes
Authors' conclusion
Frail, elderly, VKA-experienced patients with AF switched to SD-DOAC experienced significant reductions in stroke or systemic embolism, fatal and intracranial bleeding, and death. Gastrointestinal bleeding was increased with SD-DOAC, while major bleeding and the primary net clinical outcome were similar.
Study context
- Population
- Patients with atrial fibrillation (AF) in 4 RCTs of DOAC vs warfarin; frail (frailty index above median), elderly (age ≥75 years), vitamin K antagonist (VKA)-experienced vs not meeting all 3 criteria
- Participants
- 71,683 patients · 4 RCTs
- Comparison
- Standard-dose DOAC vs warfarin in frail, elderly, VKA-experienced patients vs others
- Outcome
- Stroke or systemic embolic events, bleeding events, death, and net clinical outcome
- Follow-up
- 27 months median
Pooled result
As reported in the abstract
SD-DOAC vs warfarin by subgroup (frail, elderly, VKA-experienced vs not)
SD-DOAC vs WarfarinHazard ratio (95% CI)
net clinical outcome, frail, elderly, VKA-experienced
1.01(0.91–1.13)
net clinical outcome, without all 3 criteria; Pint = 0.028
0.89(0.85–0.93)
HR
- stroke or systemic embolism, frail, elderly, VKA-experienced (n = 5,913)
- 0.83
- stroke or systemic embolism, without all 3 criteria (n = 52,721); Pint = 0.75
- 0.81
- death, frail, elderly, VKA-experienced
- 0.95
- death, without all 3 criteria; Pint = 0.54
- 0.91
Safety
| Outcome | HR (95% CI) | |
|---|---|---|
| Major bleeding, by subgroup — SD-DOAC vs Warfarin · frail, elderly, VKA-experienced | 1.06 (0.90–1.25) | |
| Major bleeding, by subgroup — SD-DOAC vs Warfarin · without all 3 criteria | 0.82 (0.76–0.89) | |
| GI bleeding, by subgroup — SD-DOAC vs Warfarin · frail, elderly, VKA-experienced | 1.83 (1.42–2.36) | |
| GI bleeding, by subgroup — SD-DOAC vs Warfarin · without all 3 criteria | 1.23 (1.09–1.39) | |
| 0.512Hazard ratio (log scale) |
- Major bleeding, by subgroup: Pint = 0.007
- GI bleeding, by subgroup: Pint = 0.006
Fatal and intracranial bleeding
- Significantly reduced with SD-DOAC in both subgroups to a similar degree
- both Pint > 0.05
Original publication
Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin. J Am Coll Cardiol. Published 12 August 2025. doi:10.1016/j.jacc.2025.05.060
Summarised from the published abstract; every number is checked against it