The Efficacy and Safety of Non-vItamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF)

Atrial fibrillation (AF) increases the risk of stroke, and oral anticoagulation is strongly recommended for patients at high thromboembolic risk. However, for patients with intermediate stroke risk, defined as a CHA₂DS₂-VASc score of 1 in men or 2 in women, randomized evidence supporting anticoagulation remains limited.

The SINGLE-AF trial is an investigator-initiated, multicenter, open-label, adjudicator-masked, superiority randomized trial conducted in South Korea. Eligible patients with AF and intermediate stroke risk are randomly assigned in a 1:1 ratio to receive direct oral anticoagulant (DOAC) therapy or no anticoagulant therapy. Patients assigned to anticoagulation receive a direct oral anticoagulant, primarily apixaban or rivaroxaban. Patients assigned to no anticoagulant therapy do not receive routine oral anticoagulation, although temporary anticoagulation is permitted around rhythm-control procedures when clinically indicated.

The primary objective of this trial is to determine whether DOAC therapy reduces the risk of adverse clinical events compared with no anticoagulant therapy. The primary end point is a composite of stroke, systemic embolism, major bleeding, or cardiovascular death at 24 months after randomization.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation Patients With Intermediate Stroke Risk
• Intervention / Treatment: Drug: Anticoagulation group(DOAC group)

• Study Type: Interventional
• Enrollment (Actual): 1803
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Severance Cardiovascular Hospital Yonsei University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Patient with atrial fibrillation aged between 19 and 80 years
2. CHA2DS2-VASc score of 1 (male) or 2 (female)

Exclusion Criteria

1. Significant liver (aspartate transaminase and/or alanine transaminase > 3 times the upper limit of normal or liver cirrhosis classified as Child-Pugh class B or C) or renal disease (serum creatinine ≥ 3.5 mg/dl or creatinine clearance < 30 ml/min)
2. Requiring anticoagulation due to surgery with a mechanical prosthetic valve, moderate-to-severe mitral stenosis, or deep vein thrombosis
3. Significant structural heart disease A. Moderate mitral regurgitation B. Severe valvular regurgitation or stenosis C. Dilated cardiomyopathy D. Hypertrophic cardiomyopathy E. Cardiac amyloidosis
4. Active malignancy
5. Pregnancy or breast-feeding
6. Life expectancy < 1 year
7. Refuse or unable to understand the written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Nonanticoagulation group; Standard treatment except anticoagulant for 2 years
Experimental: Anticoagulation group(DOAC group); Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) or rivaroxaban 20mg once daily (15mg once daily if meets dose-reduction criteria) for 2 years	Drug: Anticoagulation group(DOAC group); Apixaban 5mg twice daily (2.5mg twice daily if meets dose-reduction criteria) or rivaroxaban 20mg once daily (15mg once daily if meets dose-reduction criteria) for 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite outcome	Composite outcome including stroke/systemic embolism, major bleeding, and cardiovascular death	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke	Ischemic stroke specifically refers to central nervous system infarction (brain, spinal cord, or retinal cell death attributable to ischemia) accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage.	24 months
Major bleeding	The International Society on Thrombosis and Haemostasis (ISTH)/Scientific and Standardization Committee (SSC) definitions and bleeding assessment tool are useful for standardizing the reporting of bleeding symptoms. 1. Fatal bleeding. and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells.	24 months
Systemic embolism	Systemic embolism refers to emboli in the arterial circulation, and defined by both clinical and objective evidence of sudden loss of end-organ perfusion.	24 months
Cardiovascular Death	Death due to myocardial infarction, sudden cardiac death, heart failure, stroke, cardiovascular procedures, cardiovascular hemorrhage, and any case of death in which a cardiovascular cause cannot be excluded as adjudicated by a clinical events committee.	24 months
Clinically Relevant Non-Major Bleeding (CRNMB)	1. Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: i. requiring medical intervention by a healthcare professional ii. leading to hospitalization or increased level of care iii. prompting a face to face (i.e., not just a telephone or electronic communication) evaluation 2. ISTH major bleeding in non-surgical patients is defined as having a symptomatic presentation and 1: i. Fatal bleeding, and/or ii. Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or iii. Bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or more, or leading to transfusion of two or more units of whole blood or red cells.	24 months
Death	The permanent stopping of all the vital bodily activities	24 months
Transient ischemic attack (TIA)	TIA is brief episodes of neurological dysfunction resulting from focal cerebral ischemia not associated with permanent cerebral infarction.	24 months
Myocardial infarction	The definition of myocardial infarction (MI) was based on the Third Universal MI definition	24 months
Hospital admission	Hospital admission means admission of a covered person to a hospital as an inpatient for medically necessary and appropriate care and treatment of an Illness or Injury.	24 months

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2020
• Primary Completion (Actual): August 21, 2025
• Study Completion (Actual): August 21, 2025

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: safety; Atrial fibrillation; efficacy; anticoagulation; intermediate stroke risk
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Apixaban
• Other Study ID Numbers: 4-2020-0438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No