Patients with atrial fibrillation who fall into an "intermediate" stroke-risk category saw a 69% reduction in serious cardiac events when given standard blood thinners, according to results from the SINGLE-AF trial presented at the European Society of Cardiology's 2026 congress and published simultaneously in the New England Journal of Medicine. The randomized, open-label study, run across 18 centers in South Korea and led by principal investigator Boyoung Joung of Yonsei University, enrolled 1,803 people with atrial fibrillation and a CHA2DS2-VASc score of 1 in men or 2 in women — a risk band where doctors have long lacked strong trial evidence to guide treatment.
Participants were randomly assigned to receive a direct oral anticoagulant (DOAC), either apixaban or rivaroxaban, or no anticoagulation at all, and were followed for 24 months. The trial's primary endpoint — a composite of stroke, systemic embolism, major bleeding or cardiovascular death — occurred in 0.5% of patients on DOACs versus 1.5% of those with no treatment, according to results reported by the European Society of Cardiology. The benefit was driven largely by a drop in ischemic strokes, which occurred in just 0.1% of the DOAC group compared with 1.1% of the untreated group, while major bleeding rates were statistically similar between arms (0.3% versus 0.5%).
Why the caveats matter
Current guidelines treat anticoagulation as optional or uncertain for AFib patients in this intermediate-risk band, in contrast to higher-risk patients for whom blood thinners are standard. The SINGLE-AF results, covered by ScienceDaily and detailed in trial materials published ahead of the readout, could push future guideline committees to reconsider that stance. But several factors temper the findings. The trial was open-label, meaning patients and doctors knew who was receiving treatment, which can introduce bias into how outcomes are monitored and reported. The absolute number of events was small — translating to roughly nine events in the treatment group versus about 27 in the untreated group — meaning the precise size of the benefit carries real statistical uncertainty despite reaching significance. The study population was drawn entirely from South Korean centers, raising questions about how well the results generalize elsewhere. And the trial received funding support from drugmakers Samjin Pharmaceutical and Hanmi Pharmaceutical alongside South Korea's health ministry, a sponsorship structure that warrants disclosure even though the trial was publicly registered and peer-reviewed.
No blockthrough quote from the investigators accompanied the ESC release, but cardiologists reviewing the data have generally described it as a meaningful, if not yet definitive, argument for revisiting how intermediate-risk AFib patients are treated. Further trials in more diverse populations, and formal guideline review, are expected to follow before the intermediate-risk treatment standard changes broadly.