Oral Anticoagulants Reduce Stroke Risk in Atrial Fibrillation Patients

Direct oral anticoagulants were linked to reduced risk of stroke, major adverse events, and death in patients diagnosed with atrial fibrillation who carry an intermediate risk of stroke, according to clinical trial findings presented at the European Society of Cardiology Congress. The data, simultaneously published in The New England Journal of Medicine, offer the first randomized controlled trial evidence addressing a patient population that guidelines have long treated using only observational data.

Researchers in South Korea conducted the SINGLE-AF trial across 18 medical sites, randomizing 1,803 patients with atrial fibrillation and intermediate stroke risk, according to coverage by Healio. Patients in the trial had a mean age of 60.4 years, and 23.7 percent were women. Intermediate risk was defined as a CHA2DS2-VASc score of 1 for men or 2 for women. Participants assigned to the treatment arm received either apixaban at 5 mg twice daily or rivaroxaban at 20 mg once daily, administered at the discretion of their treating physician, while the control group received no anticoagulation therapy.

Clinical Trial Findings and Primary Endpoints

The primary composite endpoint—encompassing stroke, systemic embolism, major bleeding, or cardiovascular death at 24 months—occurred in 0.5 percent of patients in the direct oral anticoagulant group compared with 1.5 percent in the control group, according to trial presentations detailed by Healio. That yielded a hazard ratio of 0.31, indicating a statistically significant reduction in risk.

The primary endpoint of stroke, systemic embolism, major bleeding or death from CV causes at 24 months occurred in 0.5% of the DOAC group compared with 1.5% of the control group — Boyoung Joung, director of the Yonsei Heart Rhythm Center at Severance Hospital, Yonsei University College of Medicine

When examining specific clinical outcomes, stroke alone occurred in 0.3 percent of patients receiving direct oral anticoagulants compared with 1.1 percent in the untreated control group. Researchers observed no difference between the two cohorts regarding systemic embolism or major bleeding. Furthermore, no cardiovascular deaths occurred in either study arm during the observation period.

Implications for Clinical Guidelines and Health Policy

Prior to this trial, medical guidelines categorized anticoagulation for intermediate-risk atrial fibrillation patients as a class IIa recommendation, yet that guidance relied on observational studies with highly variable results, as explained by Boyoung Joung, professor of cardiology and director of the Yonsei Heart Rhythm Center at Severance Hospital, Yonsei University College of Medicine in Seoul, South Korea.

The reason why we performed this study was because the guideline recommends anticoagulation as class IIa in this population; however, the guideline is based on observational studies — Boyoung Joung

Joung noted during a press conference reported by Healio that the trial provides the necessary randomized controlled trial data to support direct oral anticoagulant therapy in this specific patient group. Beyond clinical practice, investigators hope the data will influence healthcare policy, noting that when the trial commenced a decade ago, the Korean government did not reimburse oral anticoagulation therapy for males with a CHA2DS2-VASc score of 1 or females with a score of 2.

Understanding Atrial Fibrillation and Stroke Pathology

Atrial fibrillation is the most common heart rhythm disorder globally, characterized by uncoordinated electrical activation of the atria that impairs effective contraction and promotes blood clot formation. The global prevalence reached an estimated 50 million individuals by 2020. The condition nearly doubles the risk of death, increases stroke risk by 2.4 times, doubles the risk of sudden cardiac death, and raises heart failure risk by five times.

Structural and electrophysiological alterations known as atrial myopathy drive the progression of atrial fibrillation by facilitating rapid, irregular impulses. This erratic electrical activity induces hemostasis, endothelial dysfunction, and hypercoagulability within the left atrium, particularly inside the left atrial appendage—a muscular pouch where complex morphology and restricted blood flow create an environment for thrombus development and subsequent cardioembolic strokes.