ESC Congress 2026: Randomized trial backs DOAC use in intermediate-risk AF

Clinical takeaway: For patients with atrial fibrillation and an intermediate stroke risk (CHA₂DS₂-VASc score of 1 in men or 2 in women), DOAC therapy reduced thromboembolic events compared with no anticoagulation in a randomized trial, without a clear increase in major bleeding.

Current US and European guidelines recommend considering, but not necessarily prescribing, anticoagulation for this large "gray-zone" population because randomized evidence has been lacking. The SINGLE-AF trial, presented at the 2026 European Society of Cardiology Congress and published in the New England Journal of Medicine, provides the first randomized data directly comparing a DOAC with no anticoagulation in these patients.

In the multicenter South Korean trial, 1,803 adults with atrial fibrillation and intermediate stroke risk were randomized to receive a direct oral anticoagulant (primarily apixaban or rivaroxaban) or no anticoagulation and were followed for 24 months. Average age was 60 years, nearly three-quarters were men, and most had paroxysmal atrial fibrillation.

The primary composite outcome of stroke, systemic embolism, major bleeding, or cardiovascular death occurred in 0.5% of patients receiving a DOAC versus 1.5% of those receiving no anticoagulation, representing an approximately 69% relative reduction and an absolute reduction of 1 percentage point. Stroke alone occurred in 0.3% versus 1.1% of patients, respectively. Ischemic stroke or systemic embolism was reduced from 1.1% to 0.1%.

Major bleeding rates were low and similar between groups (0.3% with DOAC therapy vs 0.5% without anticoagulation). Serious adverse events also occurred at comparable rates, affecting 8.9% and 9.3% of patients, respectively. However, investigators cautioned that the overall number of events was small, limiting the precision of the treatment estimates.

"As shown by the contemporary event rates in our trial, even patients at intermediate risk retain a residual thromboembolic vulnerability that may benefit from targeted risk reduction through oral anticoagulation," the investigators wrote, while noting that confirmatory studies are needed to better define the magnitude of benefit.

Source: Kim D, et al. (2026 Aug 28) N Engl J Med. Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk