DOACs reduce adverse clinical events in AF with intermediate stroke risk
ESC Congress 2026 – In the randomized SINGLE-AF trial, DOAC therapy reduced the risk of a composite of stroke, systemic embolism, major bleeding, or CV death at 24 months compared with no anticoagulation in patients with AF at intermediate stroke risk.
This summary is based on the presentation of Boyoung Joung, MD, PhD (Seoul, Korea) at the ESC Congress 2026 - SINGLE-AF: Anticoagulation for atrial fibrillation with intermediate stroke risk.
Introduction and methods
Current AF guidelines indicate that oral anticoagulation may be considered (class IIa recommendation) in patients at intermediate stroke risk, defined as a CHA₂DS₂-VASc score of 1 in men or 2 in women. However, this recommendation has been based on limited evidence from randomized trials.
The SINGLE-AF (Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants for Intermediate Stroke Risk in Patients with Atrial Fibrillation) trial evaluated whether DOAC therapy reduces adverse clinical events compared with no anticoagulation in patients with AF at intermediate risk of stroke.
SINGLE-AF was a prospective, multicenter, open-label, RCT that was conducted at 18 centers in South Korea. A total of 1803 patients with AF and a CHA₂DS₂-VASc score of 1 in men or 2 in women were randomized 1:1 to DOAC therapy (n=902) or no anticoagulation (n=901). In the DOAC group, patients primarily received apixaban or rivaroxaban.
The primary endpoint was net adverse clinical event, defined as a composite of stroke, systemic embolism, major bleeding, or CV death at 24 months. Secondary endpoints included the individual components of the primary endpoint, all-cause death, transient ischemic attack, clinically relevant nonmajor bleeding, MI, and hospitalization for any cause.
Main results
- At 24 months, the cumulative incidence of the primary endpoint was 0.5% with DOAC therapy and 1.5% with no anticoagulation, corresponding to an absolute difference of −1.0 percentage points (95%CI: −2.0 to −0.1; HR: 0.31; 95%CI: 0.10–0.94; P=0.03).
- The cumulative incidence of stroke was 0.3% with DOAC therapy and 1.1% with no anticoagulation (HR: 0.30; 95%CI: 0.08–1.08).
- The cumulative incidence of systemic embolism was 0% with DOAC therapy and 0.1% with no anticoagulation.
- The cumulative incidence of major bleeding was 0.3% with DOAC therapy and 0.5% with no anticoagulation (HR: 0.75; 95%CI: 0.17–3.35).
- Clinically relevant nonmajor bleeding occurred with a cumulative incidence of 2.5% and 1.6%, respectively (HR: 1.58; 95%CI: 0.81–3.08).
- In a post hoc analysis, the cumulative incidence of ischemic stroke or systemic embolism was 0.1% with DOAC therapy versus 1.1% with no anticoagulation (HR: 0.10; 95%CI: 0.01–0.77), while the cumulative incidence of major or clinically relevantnonmajor bleeding was 2.7% versus 2.0%, respectively (HR: 1.42; 95%CI: 0.76–2.63).
- The effect of DOAC therapy on the primary endpoint appeared consistent across prespecified subgroups.
Conclusion
In the SINGLE-AF trial, DOAC therapy reduced the risk of the composite of stroke, systemic embolism, major bleeding, or CV death compared with no anticoagulation in patients with AF at intermediate stroke risk. Major bleeding rates were low and similar between groups. However, because the overall number of events was small and the study included only patients from South Korea, the magnitude and generalizability of the observed benefit require confirmation in additional studies.
- Our reporting is based on the information provided at the ESC Congress 2026 -