Atrial Fibrillation, Catheter Ablation, Obesity & Overweight
Conditions
Keywords
Atrial Fibrillation, Tirzepatide, GIP/GLP-1 receptor agonist
Brief summary
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.
Detailed description
Eligible obese patients (or overweight patients with a weight-related comorbidity) with symptomatic paroxysmal or persistent AF undergoing catheter ablation will be screened within 28 days before the procedure. After ablation with restoration of sinus rhythm, participants will be randomized 1:1 to (a) tirzepatide plus standardized lifestyle intervention and standard AF management, or (b) standardized lifestyle intervention and standard AF management alone. Randomization is stratified by study center, AF type (paroxysmal/persistent), baseline BMI, and diabetes status. A 90-day post-ablation blanking period (Day 0-90) is excluded from the primary efficacy assessment. The primary efficacy assessment window runs from Day 91 to Day 365. Tirzepatide is administered subcutaneously once weekly and titrated per the China NMPA label using an individualized dose-adjustment SOP, continuing through Week 52. Both groups receive guideline-directed periprocedural anticoagulation, standardized antiarrhythmic drug (AAD) use, an individualized exercise prescription, a modified Mediterranean diet (target intake = total energy expenditure - 500 kcal), and management of smoking, alcohol, comorbidities, sleep, and obstructive sleep apnea (OSA). Approximately 8-12 tertiary (Class 3A) hospitals in China with mature AF ablation teams will participate. Planned enrollment is 710 participants.
Interventions
DRUGTirzepatide
Dual GIP and GLP-1 receptor agonist administered as a weekly subcutaneous injection. Titrated from 2.5 mg/week to a target of 10 mg/week over 12 weeks, then maintained at the maximum tolerated dose for the remainder of the 52-week treatment period.
BEHAVIORALStructured Lifestyle Intervention
Guideline-directed AF management (rate/rhythm control, anticoagulation by CHA2DS2-VASc). Structured lifestyle intervention: 500 kcal/day caloric deficit; exercise prescription of ≥150 min/week moderate aerobic; smoking cessation and alcohol moderation counseling.
Sponsors
Yunlong Wang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years and ≤75 years at the time of screening * Documented symptomatic paroxysmal AF or persistent AF, confirmed by 12-lead ECG, Holter monitoring, or cardiac monitoring device, with documented AF episode duration ≥7 days (for persistent AF) and total AF history duration ≤5 years * Body weight criteria (aligned with NMPA-approved tirzepatide indication) meeting at least one of the following: 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) * Failed response to or intolerance of at least one antiarrhythmic drug (AAD), or explicit patient preference for a rhythm control strategy * Undergoing catheter ablation for AF at a participating center, with confirmed successful restoration of sinus rhythm at the end of the procedure (as determined by the operator) * Willing and able to understand the study procedures, provide written informed consent, and comply with all protocol requirements including 12-month follow-up visits * Capable of performing basic physical activity (no absolute contraindication to moderate-intensity aerobic exercise)
Exclusion criteria
Cardiovascular
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia | Day 91 through Week 52 after catheter ablation | Any documented atrial arrhythmia - defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) - lasting ≥30 seconds, in the absence of antiarrhythmic drug (AAD) use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Monitoring Time Spent in Atrial Fibrillation (AF Burden) | At Week 12, Week 26, and Week 52 | Percentage of total monitoring time spent in AF, measured by 7-day ambulatory ECG patch. |
| Change in body weight | Baseline to Week 52 | Absolute and percentage change in body weight from baseline to baseline to 52 weeks. |
| Change in BMI | Baseline to Week 52 | Change from baseline to 52 weeks in body mass index (kg/m²) |
| Change in waist circumference | Baseline to Week 52 | Change from baseline to 52 weeks waist circumference (cm). |
| Change in left atrial volume index (LAVI) | Baseline to Week 52 | Change in echocardiographic LAVI (mL/m²) from baseline to 52 weeks measured by core laboratory. |
| Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) | Baseline to Week 52 | Change in serum NT-proBNP concentration from baseline to 52 weeks, measured by central laboratory. |
| Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) Concentration | Baseline to Week 52 | Change in serum high-sensitivity C-reactive protein (hs-CRP) concentration from baseline to 52 weeks, measured by central laboratory. |
| Time to Cardiovascular Death | Day 1 through Week 52 | Time to cardiovascular death. |
| Time to Death From Any Cause | Day 1 through Week 52 | Time to death from any cause. |
Outcome results
None listed