Blood thinners cut strokes in people with AF at a middling risk

Millions of people with atrial fibrillation sit in a grey zone. Their risk of stroke is raised, but not by enough for doctors to agree on whether a blood thinner is worth taking. A Korean trial presented at ESC Congress 2026 in Munich now offers the first randomised evidence for this group, and it points towards treatment.

In SINGLE-AF, people with atrial fibrillation (AF) at intermediate stroke risk who took a modern blood thinner had about a third of the serious events seen in people who took none. Strokes fell, and major bleeding did not rise. The catch is that events were rare in both groups, so the absolute benefit was small and the numbers behind it are thin.

The results were presented by Professor Boyoung Joung of Yonsei University in Seoul in the Hot Line 1 session on 28 August 2026, at 11:15 Munich time (11:15 in Madrid), and published at the same time in the New England Journal of Medicine.

Why AF raises stroke risk

AF is the most common heart rhythm problem. Instead of contracting in a steady rhythm, the upper chambers of the heart (the atria) quiver. Blood can pool and form clots, particularly in a small pouch called the left atrial appendage. A clot that breaks away can reach the brain and cause a stroke. Strokes linked to AF tend to be larger and more disabling than average.

Blood thinners (anticoagulants) cut that risk sharply. The trade-off is bleeding, including the rare but serious risk of bleeding into the brain. For people at high risk of stroke, the balance clearly favours treatment. For people at very low risk, it clearly doesn't. The difficulty is the middle.

How doctors score stroke risk

Doctors usually estimate stroke risk in AF with a simple points score. The version used in the latest European guidelines is called CHA2DS2-VA. Each letter stands for a risk factor:

• Congestive heart failure (1 point)
• High blood pressure (1 point)
• Age 75 or over (2 points)
• Diabetes (1 point)
• Previous stroke, mini-stroke or clot (2 points)
• Vascular disease, such as a previous heart attack or narrowed leg arteries (1 point)
• Age 65 to 74 (1 point)

An older version, CHA2DS2-VASc, also gave a point for female sex. SINGLE-AF enrolled people with a score of 1 on the older scale for men or 2 for women, which equates to a score of 1 on the newer one. In practice, that is someone with AF and just one extra risk factor, such as high blood pressure, or someone aged 65 to 74 with nothing else.

Guidance for this group has been cautious. The 2024 European Society of Cardiology (ESC) guidelines say anticoagulation should be considered at a CHA2DS2-VA score of 1, a weaker recommendation based on expert opinion and observational data. Observational studies, many from the era of warfarin, have reached conflicting answers.

"Evidence from observational studies with anticoagulants, particularly vitamin K antagonists, remains conflicting in those at intermediate risk," Joung said. "SINGLE-AF was conducted to provide the first evidence from a randomised trial on whether newer direct oral anticoagulants are beneficial in patients with AF at intermediate risk of stroke."

The SINGLE-AF trial

SINGLE-AF (NCT04437654) was an open-label randomised trial run at centres in South Korea and funded by the South Korean Ministry of Health and Welfare. It enrolled 1,803 people with AF and one stroke risk factor. Their average age was 60.4 years, and 23.7% were women.

Participants were randomly assigned to one of two strategies:

• A direct oral anticoagulant (DOAC), either apixaban 5 mg twice a day or rivaroxaban 20 mg once a day (902 people)
• No anticoagulation (901 people)

DOACs are the newer generation of blood thinners. Unlike warfarin, they don't need regular blood tests to adjust the dose, and they carry a lower risk of bleeding into the brain.

People were followed for 24 months. The main measure was a combination of four outcomes: stroke, systemic embolism (a clot blocking an artery elsewhere in the body), major bleeding and death from cardiovascular causes. Combining benefits and harms in one measure was meant to capture the net effect of treatment.

What the trial found

Over two years, the combined outcome occurred in 4 people (0.5%) in the DOAC group and 13 people (1.5%) in the group without anticoagulation. That is a 69% lower relative risk (hazard ratio 0.31, 95% confidence interval 0.10 to 0.94, p=0.03). In absolute terms, the difference was 1.0 percentage point, with a confidence interval from 2.0 to 0.1 points.

Put another way, about 100 people would need to take a DOAC for two years to prevent one of these events, based on the central estimate.

The difference came mainly from stroke:

Ischaemic strokes, the kind caused by a blocked artery, were the main driver, at 0.1% with a DOAC against 1.1% without. Systemic embolism was similar between the groups. Major bleeding was low in both, at 0.3% and 0.5%. No one in either group died of cardiovascular causes during the trial. Serious adverse events of any kind were reported at similar rates.

"We now have evidence from a randomised trial that patients with AF at intermediate stroke risk benefit from DOAC therapy, without an increase in major bleeding," Joung said. "Data from the SINGLE-AF trial may be used to inform future guideline recommendations and reimbursement policies."

Speaking to Healio, he described it as the first randomised trial to show that DOAC therapy can benefit this group.

Why the bleeding result stands out

Most trials of blood thinners show a clear rise in bleeding. That is the usual price of preventing clots. In SINGLE-AF, major bleeding was slightly lower with a DOAC than without one, although the numbers were far too small to say whether that is a real difference or chance.

Several factors may explain the low bleeding rates. Participants were relatively young for an AF population, at around 60, and by definition had few other health problems. Age, kidney disease and previous bleeding are among the strongest predictors of bleeding on anticoagulants, and people at intermediate stroke risk tend to have fewer of them. The DOACs used, apixaban and rivaroxaban, were given at standard doses.

The limits of the evidence

The headline result is statistically significant, but it rests on very few events. Only 17 people in the entire trial had a primary outcome event. A shift of a handful of events in either direction could have changed the conclusion, and the wide confidence interval (a hazard ratio anywhere from 0.10 to 0.94) reflects that uncertainty.

Other points to weigh:

• One country. All participants were from South Korea. Stroke and bleeding rates on anticoagulants differ between populations. East Asian people, for example, have historically had higher rates of bleeding into the brain on warfarin. The results may not transfer directly to Europe or North America.
• Open label. Participants and their doctors knew who was taking a blood thinner. Outcomes such as stroke and major bleeding are fairly objective, but knowledge of treatment can influence how closely people are monitored.
• Short follow-up. Two years is a short time for a treatment people may take for decades. The balance of stroke prevention and bleeding could change as people age.
• Low absolute risk. Even without a blood thinner, the stroke rate was about 1.1% over two years. For an individual, the choice involves a daily tablet, its cost and a small ongoing bleeding risk, set against a modest reduction in an already low risk.

Rod Passman, a cardiologist at Northwestern University in Chicago, made that point in comments on the trial. The risk of stroke in this group is still less than 1%, he noted, which calls for a careful discussion with each patient.

What it could mean for patients

For people with AF and one stroke risk factor, SINGLE-AF strengthens the case for offering a DOAC, particularly where bleeding risk is low. It doesn't make treatment mandatory. The decision will still depend on individual preferences, other health conditions, and how a person weighs a small reduction in stroke risk against taking a blood thinner every day.

Guideline committees may use the data to firm up their advice. The current European recommendation for this group is based on lower-grade evidence, and SINGLE-AF is the first randomised trial to address it directly. Joung also mentioned reimbursement, which matters in health systems where DOACs are only funded above a certain risk score.

Larger trials in other populations would help settle how far the findings apply. Until then, anyone with AF who is unsure whether they should be taking a blood thinner should discuss it with their GP or cardiologist. People shouldn't start or stop anticoagulants without medical advice.