J Am Coll Cardiol

Switching from warfarin to DOACs linked to improved outcomes in older afib patients

August 11, 2025

Study details: This COMBINE-AF substudy analyzed 71,683 patients with afib across four randomized trials comparing standard-dose (SD) direct oral anticoagulants (DOACs) vs warfarin. Frailty was assessed using a modified Rockwood index. The focus was on 5,913 frail, elderly (≥75 years), VKA-experienced patients. Prespecified outcomes included stroke or systemic embolic events, bleeding events, death, and a net clinical outcome combining these events.

Results: After a median 27-month follow-up, stroke/systemic embolism and death rates were similarly reduced with SD-DOACs in both frail and non-frail groups. Major bleeding was similar with SD-DOAC compared with warfarin in frail, elderly, VKA-experienced patients (hazard ratio [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). Similarly, the net clinical outcome was similar in the frail, elderly, VKA-experienced patients with SD-DOAC compared with warfarin (HR, 1.01; 95% CI, 0.91-1.13), while it was significantly reduced with SD-DOAC patients without all 3 criteria (HR, 0.89; 95% CI, 0.85-0.93]). Fatal and intracranial bleeding were significantly reduced with SD-DOAC in both subgroups to a similar degree. However, GI 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) relative to those without all 3 criteria (HR, 1.23; 95% CI, 1.09-1.39).

Clinical impact: SD-DOACs are a reasonable alternative to warfarin in frail, elderly, VKA-experienced patients with afib, offering protection against stroke and serious bleeding. However, clinicians should monitor for GI bleeding and individualize anticoagulant choice based on bleeding risk profiles.

Source:

Nicolau AM, et al. (2025, August 12). J Am Coll Cardiol. Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin: The COMBINE-AF Substudy. https://pubmed.ncbi.nlm.nih.gov/40769671/