# COMBINE AF: overstap naar nieuwer anticoagulans versus warfarine bij ouderen

*geplaatst 2025-08-12 · Atriumfibrilleren · Journal of the American College of Cardiology · doi 10.1016/j.jacc.2025.05.060 · https://hartvaat.nl/2025/08/12/combine-af-overstap-naar-nieuwer-anticoagulans-versus-warfarine-bij-ouderen/*

Analyse onderzocht de uitkomsten bij ouderen die overstapten van warfarine naar een NOAC versus op warfarine bleven. Overstap was veilig en geassocieerd met minder bloedingen.

## English: Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin: The COMBINE-AF Substudy.

This COMBINE-AF analysis showed that switching from warfarin to a NOAC in older AF patients is associated with improved outcomes compared with remaining on warfarin, supporting anticoagulant modernization even in the elderly.

## Abstract (original, from the publication)

BACKGROUND: Whether frail, elderly patients with atrial fibrillation (AF) on a vitamin K antagonist (VKA) should switch to a direct-acting oral anticoagulant (DOAC) was studied in the FRAIL-AF trial and remains controversial. OBJECTIVES: The purpose of this study was to evaluate, in the COMBINE-AF data set, the impact on clinical outcomes of switching frail, elderly AF patients from VKA to DOAC. METHODS: COMBINE-AF consists of individual patient-level data from 71,683 patients with AF in 4 randomized clinical trials comparing DOAC vs warfarin. Frailty was evaluated using a frailty index derived from a modified Rockwood's Accumulation Model including 18 age-related conditions. Patients with a frailty index score above the median were considered frail. Prespecified outcomes were stroke or systemic embolic events, bleeding events, death, and a net clinical outcome combining these events. RESULTS: We identified 5,913 patients who were frail, elderly (age ≥75 years), and VKA-experienced and 52,721 patients who did not meet all 3 of these criteria. Patients were randomized to a standard-dose (SD) DOAC or warfarin. After 27 months median follow-up, there was no heterogeneity in treatment effect with SD-DOAC vs warfarin among those who met all 3 criteria vs those who did not for the endpoints of stroke or systemic embolic events (HR: 0.83 vs 0.81; Pint = 0.75) or for death (HR: 0.95 vs 0.91; Pint = 0.54). Major bleeding was similar with SD-DOAC vs warfarin in frail, elderly, VKA-experienced patients (HR: 1.06 [95% CI: 0.90-1.25]), while it was significantly reduced with SD-DOAC in patients without all 3 criteria (HR: 0.82 [95% CI: 0.76-0.89]; Pint = 0.007). Likewise, the net clinical outcome was similar in the frail, elderly, VKA-experienced patients with SD-DOAC vs warfarin (HR: 1.01 [95% CI: 0.91-1.13]), while significantly reduced with SD-DOAC patients without all 3 criteria (HR: 0.89 [95% CI: 0.85-0.93]; Pint = 0.028). Fatal and intracranial bleeding were significantly reduced with SD-DOAC in both subgroups to a similar degree (both Pint > 0.05), while gastrointestinal bleeding with SD-DOAC was increased to a greater degree in frail, elderly, VKA-experienced patients (HR: 1.83 [95% CI: 1.42-2.36]) compared with those without all 3 criteria (HR: 1.23 [95% CI: 1.09-1.39]; Pint = 0.006). CONCLUSIONS: 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. Based on these findings, SD-DOAC is a reasonable choice for frail, elderly, VKA-experienced patients to reduce stroke and systemic embolism, death, and the most serious types of bleeding.

Auteurs: Andre M Nicolau, Robert P Giugliano, Andre Zimerman, Jonathan Afilalo, Baris Gencer, Jan Steffel, Michael G Palazzolo, John W Eikelboom, Christopher B Granger, Manesh R Patel, Renato D Lopes, Bernard J Gersh, Belal Suleiman, Joris R de Groot, Mauricio I Scanavacca, Christian T Ruff, Elliott M Antman, Eugene Braunwald, Lars Wallentin

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Bron: Journal of the American College of Cardiology, https://doi.org/10.1016/j.jacc.2025.05.060. Bijgewerkt 2026-07-03T13:30:47Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.