Blood Thinners Cut Major Complications by 69% in Atrial Fibrillation Trial

A randomized trial has found that common blood thinners can cut the risk of stroke and other serious complications in people with atrial fibrillation (AF) whose stroke risk falls into an unclear middle zone. The SINGLE-AF trial, the first randomized study of direct oral anticoagulants (DOACs) in this "intermediate risk" group, found the drugs cut the combined risk of stroke, systemic embolism, major bleeding, or cardiovascular death by 69% over two years.

Atrial fibrillation causes the heart's upper chambers to beat irregularly, letting blood pool and form clots that can travel to the brain and cause a stroke. Current heart-rhythm guidelines strongly recommend anticoagulants for AF patients at high stroke risk, but for intermediate-risk patients the recommendation is weaker, since prior evidence came from conflicting observational studies.

The open-label trial enrolled 1,803 people with AF and an intermediate stroke risk (a CHA₂DS₂-VASc score of 1 in men or 2 in women) at 18 centers in South Korea. Participants were randomly assigned to no anticoagulant or a DOAC — apixaban 5 mg twice daily or rivaroxaban 20 mg once daily — drugs that act directly on clotting proteins, unlike older vitamin K antagonists.

After 24 months, the primary outcome occurred in 0.5% of patients on a DOAC versus 1.5% of those on no anticoagulant — a 69% relative reduction and a 1-percentage-point absolute difference. The benefit came largely from fewer ischemic strokes (0.1% versus 1.1%), and major bleeding was not higher in the DOAC group (0.3% versus 0.5%).

"We now have evidence from a randomized trial that patients with AF at intermediate stroke risk benefit from DOAC therapy, without an increase in major bleeding," said principal investigator Professor Boyoung Joung of Yonsei University in Seoul, South Korea. The trial was presented at ESC Congress 2026, published in the New England Journal of Medicine, and funded by South Korea's Ministry of Health and Welfare, Samjin Pharmaceutical, and Hanmi Pharmaceutical.