The Efficacy and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Intermediate Stroke Risk in Patients With Atrial Fibrillation

doi:10.1056/nejmoa2607978

SINGLE-AF

Patient / Population Intervention / Exposure Comparison Outcome

In 1,803 patients with atrial fibrillation at intermediate stroke risk, a direct oral anticoagulant reduced the net composite of stroke, embolism, major bleeding and death at 2 years compared with no anticoagulation.

N

1,803patients

Design

Investigator-initiated, multicentre, open-label, superiority RCT with blinded outcome adjudication (PROBE), 1:1, permuted blocks stratified by centre, 24-month follow-up, South Korea

Endpoint

Composite of stroke, systemic embolism, ISTH major bleeding and cardiovascular death at 2 years

Relevance

2Important — one of several pillars.

Result0.5% vs 1.5% at 24 months (HR 0.31, 95% CI 0.10-0.94; P = 0.03), driven by ischaemic stroke (0.1% vs 1.1%). Major bleeding 0.3% vs 0.5%.

Kim D, Lee Y, et al. N Engl J Med. 2026; published online 28 August. 10.1056/nejmoa2607978

Discussion & critique

The first randomised answer for atrial fibrillation with a single stroke risk factor, and it favours anticoagulating. Fewer than 20 primary events across 1,803 patients carry the result: the interval runs to 0.94, so the direction is firmer than the size. Open-label at 18 Korean centres, with an observed event rate far below the planning assumption and an absolute difference of one percentage point.