Obese patients with atrial fibrillation (AF) have a high recurrence rate after catheter ablation, even at experienced centers. Weight reduction improves post-ablation outcomes, but lifestyle measures alone are difficult to sustain. Tirzepatide, a once-weekly GIP/GLP-1 dual receptor agonist, produces greater weight loss than GLP-1 monotherapy and may confer additional cardiometabolic benefits. This multicenter, randomized, open-label, parallel-group, superiority trial evaluates whether adding standardized tirzepatide treatment to a structured lifestyle intervention - compared with the lifestyle intervention alone - reduces AF recurrence within 1 year after ablation in obese patients.
Inclusion Criteria:
BMI ≥28.0 kg/m² (obesity threshold per Chinese criteria), OR BMI ≥24.0 kg/m² and <28.0 kg/m² (overweight per Chinese criteria) with at least one weight-related comorbidity: hypertension, dyslipidemia, type 2 diabetes mellitus (T2DM), obstructive sleep apnea syndrome (OSAS), or atherosclerotic cardiovascular disease (ASCVD)
Exclusion Criteria:
Cardiovascular Exclusion Criteria
Tirzepatide-Specific Exclusion Criteria (per NMPA Prescribing Information)
General Exclusion Criteria
Participants and treating physicians are unmasked. All rhythm events are adjudicated by an independent blinded Clinical Endpoint Committee (CEC).
Imaging and biomarker core laboratories operate in blinded fashion. Statistician is blinded until the primary analysis is locked.
Standardized lifestyle intervention and standard AF management plus once-weekly subcutaneous tirzepatide, initiated after randomization and continued through Week 52. Tirzepatide titration (per NMPA label): * Weeks 1-4: 2.5 mg once weekly (initiation) * Weeks 5-16: escalate by 2.5 mg every 4 weeks (5 mg → 7.5 mg → 10 mg) * Weeks 17-52: maintenance 10 mg once weekly, up-titratable to 15 mg (maximum dose 15 mg)
AF Management and Post-Ablation Care * Ablation technique: circumferential pulmonary vein isolation (CPVI) ± adjunctive linear ablation at operator discretion, using established mapping and energy delivery protocols * Peri-procedural anticoagulation: guideline-directed anticoagulation * Antiarrhythmic drug (AAD) use: standardized per protocol SOP; Exercise Intervention • Target: moderate-intensity aerobic exercise ≥150 minutes per week, OR vigorous-intensity aerobic exercise ≥75 minutes per week Dietary Intervention • Caloric target: estimated total energy expenditure (TEE) minus 500 kcal/day Other Risk Factor Management * Smoking cessation * Alcohol restriction * Comorbidity management * OSA management
Tirzepatide on Atrial Fibrillation Recurrence After Catheter Ablation in Patients With Obesity and HFpEF
Tirzepatide to Reduce rEcurrence And Burden After Ablation of Atrial Fibrillation
TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation
Effect of Tirzepatide on Cardiovascular and Metabolic Parameters in Obese Adult Patients With Congenital Heart Disease
Effect of Complex Weight-reducing Interventions on Rhythm Control in Obese Subjects With Atrial Fibrillation
Outcome of Overweight AF Patients Following Ablation With a Potential Weight Loss Medication ( GOAL-AF )
A Study of Tirzepatide (LY3298176) In Participants After A Lifestyle Weight Loss Program
Impact of Life-Style Modification On Ablation Outcome in Atrial Fibrillation