ACCEL Lite: SINGLE-AF: Anticoagulation For AFib With Intermediate Stroke Risk

The SINGLE-AF study evaluated whether direct oral anticoagulant (DOAC) therapy improves outcomes in patients with atrial fibrillation (AFib) who are at intermediate risk of stroke. The primary goal was to determine the net clinical benefit of anticoagulation compared with no anticoagulant therapy. The findings support the use of DOACs in appropriately selected patients with intermediate stroke risk.

In this episode, Dhanunjaya Lakkireddy MBBS, FACC and Boyoung Joung, MD discuss SINGLE-AF: Anticoagulation for atrial fibrillation with intermediate stroke risk.

Full Transcript follows:

TRANSCRIPT Lakkireddy-Joung interview, Nov. 2, 2026

Hello, this is Alison Bailey, your editor-in-chief for ACCEL. Welcome to the ACCEL Lite Podcast. Now, here's your episode.

Lakkireddy: Hello, I'm Dhanunjaya Lakkireddy, Executive Medical Director for the Kansas City Heart Rhythm Institute. I'm also an associate editor at the ACCEL Studios for the American College of Cardiology. Today we have the distinct pleasure of having Boyoung Joung, Professor of Medicine, University of Yonsei College of Medicine from Seoul, South Korea. He recently presented his fantastic study, SINGLE AF: Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk.

This is an important subcategory. We really needed more data. And I think Dr. Joung and team has really done an excellent job at studying this and presenting the data at the recent ESC, which was a late breaking clinical trial and also came out as a publication in the New England Journal of Medicine. Dr. Joung, welcome to ACCEL.

Joung: Thank you very much, Dr. Lakkireddy. I'm happy to share our SINGLE AF trial with the audience.

Lakkireddy: Alrighty. So just to get started, what was the purpose of the study? What prompted you to think about this question and what was the main results?

Joung: First, when we designed the single AF trial, recommendation for oral anticoagulation in AF patient with an intermediate stroke risk, CHA₂DS₂-VASc score 1 for male, and 2 for female differed across international guidelines. Most current AF guidelines now provide a class 2A recommendation. However, this recommendation has not been based on randomized control trial. And moreover, when we started the trial the big issue in Korea was that our government reimbursed DOAC for women and CHA₂DS₂-VASc 2 but not for men with CHA₂DS₂-VASc 1. So this was the government-funded study and object was to evaluate whether DOAC lowered adverse clinical event compared with no anticoagulation in patient with AF at intermediate stroke risk. The main result was DOAC therapy actually lowered adverse clinical event compared to no drug therapy in our SINGLE AF trial.

Lakkireddy: All right. So Dr. Joung, can you tell us more about your study design and the methodology? How long it took and how you went about recruiting these patients?

Joung: In this study, 1800 patients with atrial fibrillation and CHA₂DS₂-VASc 1 male or 2 female and 1:1 randomized to DOAC and no DOAC and we checked the primary outcome composite of stroke, systemic embolism, major bleeding or cardiovascular death at two years after randomization and this was the investigator initiated prospective multicenter RCT and eighteen tertiary centers in Korea participated. And baseline characteristics, mean age was about 60 years old and there was no difference between age and risk factors and genders and 76% percent was male, it means the female was sixty and 26% and about 29% was persistent atrial fibrillation, and among the risk factors, hypertension was most common with about 50%. And mean CHA₂DS₂-VASc score was 1.3 in both groups, and CHA₂DS₂-VASc score was 1 both group, and HAS-BLED score was 0.5 for both groups. And major result was the net adverse clinical event including stroke, systemic embolism, major bleeding, or cardiovascular deaths. Cumulative incidence of major endpoint was 1.5% in no DOAC group at two years and 0.5% in DOAC group at two years group, two years on follow-up period. And DOAC therapy actually lowered the risk of adverse event about 69% with P value of a 0.028.

Lakkireddy: All right. So I mean this study is primarily done in the Korean population. Do you think the results of the study can be extrapolated to other demographics, other racial and ethnic groups across the globe?

Joung: Yes, that's right. Very good question. Actually, as we mentioned at the beginning, the previous data is all observational study. Actually our data almost the same as the Swedish result. Their annual stroke risk in CHA₂DS₂-VASc score 1,CHA₂DS₂-VASc 1 annual stroke risk was about 0.5%. However, the difference is from French, they reported much higher stroke risk. So we think that our result can be applied to other races.

Lakkireddy: After all, risk of stroke remains the risk of stroke irrespective of the racial and demographic profile of individuals. So what I also found very fascinating was the overall major bleeding complications in the anticoagulation arm was relatively insignificant. I mean they tolerated the drug really well. And do you think it's primarily driven by age or what do you think happened here? Because that's one thing we worry about always, right? The risk of bleeding.

Joung: Yes, it's right, right. The mean age of our study population was 60 and only had the one risk factors. So relatively the bleeding rate in DOAC was when it count major bleeding, it was really low, less than 0.5% at two years, even DOAC and without DOAC therapy. And even we count the major bleeding over clinical element, no major bleeding, DOAC group 2.7% and no DOC group was 2.0% and there was no difference between two groups. So I think our patient population the bleeding risk is very low and they tolerate the DOAC very well.

Lakkireddy: I mean, this is really a very insightful study and what I found also equally interesting is during the twenty-four months of follow-up, the CHA₂DS₂-VASc score actually increased in these patients to a class 1 recommendation for anticoagulation thresholds in about 13% in the DOAC group and 17% in the non-anticoagulation group. Which I think really underlines the importance of continued reappraisal of the risk scores and the risk factors for patients over a period of time. So do you think this really opens up an opportunity for people to think about the dynamic nature of the risk?

Joung: Yes, yes, right. In our study even in no DOAC group, if their CHA₂DS₂-VASc from 1 to 2 increased then we started DOAC again and also we think the dynamic assessment of CHA₂DS₂-VASc score if possible at least at six months will be very important to treat this patient.

Lakkireddy: So how about the results of this trial relevant to clinical practice? Say I'm a cardiologist in the middle of Kansas and I listen to ACCEL regularly on my way to work and I want to learn something from this. What's your take-home message? How does this really impact clinical practice?

Joung: Actually for the anticoagulation for the intermediate stroke risk even the guidelines recommend Class 2A indication. I think the prescription rate may be low and also in some countries because of the reimbursement issue we have some problem in prescribing the DOAC. However, right now all four DOAC already patent finished and also the price of the drug is very cheap in many countries. So I think with this single trial result we have stronger evidence so we have to prescribe them to prevent stroke risk.

Lakkireddy: No, this is fantastic. I think you really studied a group of patients with atrial fibrillation that don't have much solid clinical data behind as a result of which the interpretation of who needs anticoagulation or not is quite heterogeneous and I think this is an important group that oftentimes was suboptimally treated. Don't you agree?

Joung: Yes, yes, right, right. That's the I think the important point of our trial.

Lakkireddy: So this is kind of what I took home from talking to you today and reading your paper. Patients who have intermediate stroke risk, which is CHA₂DS₂-VASc score of 1 in men and 2 in women, are still at risk for strokes and anticoagulating these people is important in decreasing that risk significantly while not increasing the risk of bleeding complications. It is also important to understand that over a period of time patient stroke risk evolves because they get older, they acquire other secondary comorbidities like hypertension, diabetes, and other things that continues to change their overall risk. And so having a way to assess the dynamically evolving / CHA₂DS₂-VASc score, either with the help of the EMR or continued appraisal clinically. And introduction of oral anticoagulation in an appropriate way is the way forwards.

So, Dr. Joung, thank you very much for actually doing this very important study and enriching the literature around oral anticoagulation use. And potentially the next side of guidelines will move the indication for oral anticoagulation in this subgroup from 2A to class 1 indication. Thank you very much, and thanks for joining us in the ACCEL.

Joung: Thank you very much.

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