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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
710
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.
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.
Number of Participants With Recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia
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.
Time frame: Day 91 through Week 52 after catheter ablation
Percentage of Monitoring Time Spent in Atrial Fibrillation (AF Burden)
Percentage of total monitoring time spent in AF, measured by 7-day ambulatory ECG patch.
Time frame: At Week 12, Week 26, and Week 52
Change in body weight
Absolute and percentage change in body weight from baseline to baseline to 52 weeks.
Time frame: Baseline to Week 52
Change in BMI
Change from baseline to 52 weeks in body mass index (kg/m²)
Time frame: Baseline to Week 52
Change in waist circumference
Change from baseline to 52 weeks waist circumference (cm).
Time frame: Baseline to Week 52
Change in left atrial volume index (LAVI)
Change in echocardiographic LAVI (mL/m²) from baseline to 52 weeks measured by core laboratory.
Time frame: Baseline to Week 52
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP)
Change in serum NT-proBNP concentration from baseline to 52 weeks, measured by central laboratory.
Time frame: Baseline to Week 52
Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) Concentration
Change in serum high-sensitivity C-reactive protein (hs-CRP) concentration from baseline to 52 weeks, measured by central laboratory.
Time frame: Baseline to Week 52
Time to Cardiovascular Death
Time to cardiovascular death.
Time frame: Day 1 through Week 52
Time to Death From Any Cause
Time to death from any cause.
Time frame: Day 1 through Week 52
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