Discontinuation of Anticoagulation With Intensive Rhythm Monitoring in Post-ablation Patients With Atrial Fibrillation

DIAMOND-AF is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial designed to evaluate post-catheter ablation anticoagulation management in patients with atrial fibrillation (AF/AFL). The trial will enroll adults aged 18-80 years who are 60±15 to 365±15 days after AF ablation, have a CHA2DS2-VA score ≥2, have no history of ischemic stroke/transient ischemic attack/systemic embolism, have been continuously taking a non-vitamin K antagonist oral anticoagulant (NOAC), and have no documented atrial tachyarrhythmia recurrence after ablation. Eligible participants will be randomized 1:1 to (1) discontinue NOAC immediately after randomization or (2) continue NOAC therapy. The study uses a co-primary endpoint strategy: a non-inferiority assessment for the composite efficacy endpoint (all-cause death, ischemic stroke, or systemic embolism) and a superiority assessment for the composite safety endpoint (ISTH major bleeding or ISTH clinically relevant non-major bleeding). To maximize safety while testing an anticoagulation-discontinuation strategy, all participants will undergo intensified rhythm monitoring using a smartwatch capable of single-lead ECG plus scheduled Holter/single-lead ECG patch monitoring (at least every 6 months; every 2 months encouraged), with symptom-triggered and opportunistic ECGs incorporated. AF Recurrence is defined as any ECG-confirmed atrial tachyarrhythmia (AF/AFL/atrial tachycardia) lasting ≥30 seconds; once AF recurrence is confirmed, the participant will be censored and will exit further trial follow-up. Participants will have in-person/structured study visits at months 3 and 6 after randomization, then every 6 months, with additional rhythm/anticoagulation follow-up every 2 months. The planned sample size is 4,100 participants (2,050 per group).

Inclusion criteria

Participants must meet all of the following criteria:

• Age 18 to 80 years.
• 60±15 to 365±15 days after atrial fibrillation/atrial flutter (AF/AFL) ablation.
• CHA2DS2-VA score ≥2.
• No history of stroke, transient ischemic attack (TIA), or systemic embolism.
• Continuous use of a NOAC since AF/AFL ablation.
• No documented atrial tachyarrhythmia recurrence since ablation.
• No antiarrhythmic drug (AAD) use within the past 2 months.
• Able and willing to provide written informed consent.
• Able and willing to comply with study procedures and follow-up.

Exclusion criteria

Participants will be excluded if any of the following criteria are present:

• High risk of post-ablation recurrence (e.g. including premature atrial contraction burden >3% on any ambulatory ECG/Holter recording).
• Moderate-to-severe mitral stenosis (mitral valve area ≤2.0 cm²) or mechanical heart valve.
• Increased bleeding risk, including any of the following:

• Current ISTH major bleeding or clinically relevant non-major bleeding (CRNMB).
• History of non-traumatic major bleeding (e.g., intracranial, intraocular, spinal, retroperitoneal, gastrointestinal, or intra-articular) unless the reversible cause has been permanently eliminated.
• Unresolved intracranial aneurysm/vascular malformation, or active/unhealed gastric or duodenal ulcer.
• General anesthesia surgery within the past 3 months.
• Planned surgery within the next 3 months.
• Known bleeding diathesis (e.g., hemophilia).
• Uncontrolled hypertension (SBP >180 mmHg and/or DBP >110 mmHg).
• Hemoglobin <90 g/L or blood transfusion within 4 weeks prior to enrollment.
• Platelet count <50 × 10⁹/L.
• End-stage kidney disease (eGFR <15 mL/min/1.73 m²) or on dialysis.
• Severe liver disease (e.g., esophageal variceal bleeding, ascites, hepatic encephalopathy, or jaundice).
• Known intolerance to oral anticoagulants or contraindication to oral anticoagulation.
• Any condition requiring continued oral anticoagulation (e.g., pulmonary embolism, deep vein thrombosis, hypertrophic cardiomyopathy, cardiac amyloidosis).
• Conditions associated with high non-cardioembolic stroke risk, including carotid, vertebral, or intracranial arterial stenosis ≥70%.
• Prior left atrial appendage (LAA) occlusion, surgical LAA excision/closure, or intraoperative confirmation of LAA electrical isolation.
• Female participants who are pregnant or breastfeeding, or of childbearing potential not using effective contraception.
• Life expectancy <2 years.
• Current participation in another interventional clinical trial.
• Any condition that, in the investigator's judgment, would make the participant unsuitable for the study.