The DESTINATION Study investigates whether anticoagulation therapy is necessary after successful catheter ablation (CA) for atrial fibrillation (AF). Current guidelines recommend continued anticoagulation based on stroke risk scores, even post-ablation, potentially exposing patients to unnecessary bleeding risks. This international, multicenter, randomized controlled trial aims to compare thromboembolic and bleeding event risks between patients who continue and discontinue anticoagulation after ablation. The study involves 3,160 AF patients, all free of AF recurrence within 6 months to 1 year after ablation. Smart wearable monitors will track recurrence, and patients are followed for 24 months to assess event rates. Findings may reshape anticoagulation guidelines, improving clinical practice for AF patients worldwide.

This prospective, international, multicenter randomized controlled trial (RCT) investigates the safety and necessity of continuing anticoagulation therapy after successful catheter ablation of atrial fibrillation. The study will enroll 3,160 patients who underwent catheter ablation for AF and achieved no recurrence within 6 months to 1 year post-procedure. Participants will be randomly assigned to either continue or discontinue anticoagulation therapy. Smart wearable devices will monitor AF recurrence every 3 months, detecting both symptomatic and asymptomatic events. The study's primary endpoint is a composite of ischemic stroke, systemic embolism, and major bleeding at a 24-month follow-up. Secondary outcomes include AF recurrence rates, re-ablation needs, and quality of life measures. Participants are monitored through follow-up visits at 3, 6, 12, 18, and 24 months, and data from wearable devices will be transmitted to the research team. This study is significant due to the diversity of the population, with sites in China and the US, allowing for results that are generalizable across ethnic and geographic lines. The trial's findings aim to provide high-quality evidence to inform future guideline recommendations regarding post-ablation anticoagulation therapy, potentially reducing unnecessary bleeding risks and optimizing treatment outcomes. The inclusion of smart wearable monitors enhances the detection of asymptomatic recurrences and provides continuous, reliable data on patient health during the follow-up period.

Inclusion Criteria:

• Age ≥18 years
• Diagnosed paroxysmal, persistent, or longstanding persistent AF
• Successful procedure (defined as restoration of sinus rhythm after PV isolation for paroxysmal AF, restoration of sinus rhythm after PV isolation and completion of additional ablation for persistent AF, according to 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation) and no recurrence within 3 months of ablation, using a cooled tip RF-, laser- or cryo-balloon-catheter
• No periprocedural complications
• Signed informed consent
• Male with CHA2DS2-VASC score ≥1, female with score ≥2.

Exclusion Criteria:

• Valvular AF (moderate- severe mitral insufficiency; relevant mitral stenosis with a mean pressure gradient >5mmHg)
• Reversible AF (e.g. uncontrolled hyperthyroidism)
• Prior AF ablation (including surgical ablation)
• History of left atrial appendage occlusion/ligation/excision
• Concomitant surgical ablation
• Left atrial diameter >50 mm
• Left atrial or LAA thrombus
• Pregnancy/breast feeding
• Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
• Patient has a non-arrhythmic condition necessitating long-term oral anticoagulation (i.e. PE, ventricular thrombus, peripheral thrombosis, etc)
• Recent myocardial infarction, NYHA class IV heart failure, patent foramen ovale, recent trauma or other prothrombotic conditions
• Patient with special risk factors for stroke unrelated to AF, specifically known thrombophilia/ hypercoagulability, uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg within 4 days of enrollment), untreated familial hyperlipidemia, known vascular anomaly (intracranial aneurysm/ arteriovenous malformation or chronic vascular dissection), or known severe carotid disease.
• Patient has bleeding contra-indication to oral anticoagulation (such as bleeding diathesis, hemorrhagic disorder, significant gastrointestinal bleeding within 6 months, intracranial/intraocular/ atraumatic bleeding history, fibrinolysis within 48 hours of enrollment).
• Patient has other contraindication to oral anticoagulation or treatment with antiplatelet agent
• Patient has been on strong CYP3A inducers (such as rifampicin, phenytoin, phenobarbital, or carbamazepine) or strong CYP3A inhibitors (such as ketoconazole or protease inhibitors) within 4 days of enrolment
• Structural congenital heart disease
• Recent stroke or intracranial hemorrhage within 6 months
• Inability to adequately understand nature, significance, implications and risks of study precipitation and to comply with follow-up (i.e. bipolar disorders, severe depression, suicidal tendencies, among others) as judged by the local physician, ongoing drug or alcohol addiction (> 8 drinks/week)
• Patients who are > 85 years of age
• Patients who are critically ill or who have a life expectancy <3 years
• Patient is unable or unwilling to provide informed consent
• Patient is included in another randomized clinical trial or a clinical trial requiring an insurance