The SINGLE-AF trial is testing whether people with atrial fibrillation at intermediate stroke risk do better on a direct oral anticoagulant than on nothing at all. In planning the trial, the investigators assumed a serious event would occur in 2.0% of the anticoagulant group and 4.5% of the no-anticoagulant group over two years. That would be 2.5 fewer events per 100 people treated for two years, about 25 fewer per 1,000, or roughly 40 people treated to prevent one event. Those figures are the assumptions used to calculate how many patients to enroll, not results: the trial is still running and has not reported outcomes.
Key takeaways
- The trial was sized on the assumption that treating 100 borderline-risk atrial fibrillation patients with a blood thinner for two years would prevent about 2.5 serious events.
- No outcomes have been reported yet, so there is no measured effect on stroke or on bleeding to weigh.
- This is the first randomized trial in this group, but it ran only in South Korea and only for two years.
What the study found
SINGLE-AF is a multicenter trial in South Korea enrolling 1,800 people with atrial fibrillation, 900 in each group. All of them had exactly one non-sex stroke risk factor, meaning a CHA2DS2-VASc score of 1 in men or 2 in women. Participants were 19 to 80 years old, per the trial registration.
They were randomly assigned in equal numbers to either a direct oral anticoagulant (apixaban 5 mg twice daily or rivaroxaban 20 mg once daily) or to no anticoagulation.
The primary endpoint was a combination of stroke, systemic embolism, major bleeding, and cardiovascular death at 24 months. The investigators assumed it would occur in 2.0% of the anticoagulant group and 4.5% of the no-anticoagulant group, and used that gap to set the enrollment target. The protocol counts a two-sided p value below 0.05 as statistically significant, meaning a result will be called real only if there is less than a 5 in 100 chance it came from luck alone.
Dr. Kumar’s take
This trial fills a real hole. European guidelines give a Class I recommendation for anticoagulants in high-risk atrial fibrillation, but only a Class IIa “should be considered” in the intermediate group, and the design paper published in Heart Rhythm O2 states plainly that no randomized trials had addressed the question. Doctors have been improvising in this zone for a decade.
The numbers in circulation right now are assumptions, not answers. A design paper tells you what the investigators expected before anyone was enrolled, and an expectation is not evidence. I would wait for the reported outcomes before letting any effect size into a clinical conversation.
Design matters too. Patients knew which group they were in, since there was no placebo, though the protocol specifies blinded outcome assessment, which protects the endpoint counting. The trial ran entirely in South Korea and excluded people with severe kidney or liver disease, active cancer, or a life expectancy under a year. A heavier, older, more bleeding-prone Western population may not see the same clean safety result.
Funding is worth naming. The European Society of Cardiology reports the trial was funded by the Korean Ministry of Health and Welfare along with Samjin Pharmaceutical and Hanmi Pharmaceutical, and the principal investigator reports research funds from both companies. That does not invalidate a randomized trial, but it belongs in the reader’s mind.
Two years is also short for a decision most people make for life.
What it means for you
This applies to a narrow group: atrial fibrillation with exactly one qualifying risk factor, such as high blood pressure, diabetes, heart failure, vascular disease, or age 65 to 74. If that is you, three questions are worth asking your cardiologist. What is my actual score, and which single factor is driving it? What is my bleeding risk, especially given kidney function and other medications? And do I resemble the people in this trial?
Nothing has changed in the guidelines yet. The European Society of Cardiology framed the results as evidence that “should be used to inform future guidelines,” which is not the same as a new standard of care. If you are already on an anticoagulant, do not stop it based on a news story. If you are not, this is a conversation, not an emergency.
The underlying risk factor still deserves attention. If blood pressure is what pushes your score to 1, lowering it with regular movement addresses the cause rather than the clot. Irregular sleep timing has also been linked to serious cardiac events.