Effect of Tirzepatide on Recurrence of Atrial Fibrillation After Catheter Ablation in Patients With Obese and HFpEF: A Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 602
- 试验地点
- 1
研究概览
简要总结
This multicenter, randomized, open-label, blinded-endpoint trial evaluates whether weekly subcutaneous tirzepatide for 12 months reduces atrial fibrillation (AF) recurrence after catheter ablation in adults with obesity and heart failure with preserved ejection fraction (HFpEF). HFpEF is diagnosed by direct intraprocedural measurement of mean left atrial pressure (mLAP ≥ 15 mmHg at rest) during the ablation procedure, providing a hemodynamically anchored, homogeneous study population free from the diagnostic ambiguities of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and E/e' in AF patients. Approximately 602 participants will be randomized 1:1 to tirzepatide (titrated to a target of 10 mg/week, maximum 15 mg/week) plus standard care, or standard care alone. Both groups receive an identical structured lifestyle intervention. The primary endpoint is the first documented AF/atrial flutter/atrial tachycardia episode lasting ≥ 30 seconds, occurring between day 91 and day 365 after ablation, adjudicated by an independent blinded clinical endpoint committee.
详细描述
Background and Rationale: Obesity and HFpEF are key drivers of AF onset and recurrence. In patients with both conditions, 12-month AF recurrence after catheter ablation reaches 40-55%. The LEGACY and ARREST-AF cohorts demonstrated that ≥10% weight loss approximately halves AF recurrence. Tirzepatide, a dual GIP/GLP-1 receptor agonist, achieved over 20% weight reduction in SURMOUNT-1 and improved heart failure outcomes in the SUMMIT trial of HFpEF with obesity. Whether tirzepatide reduces post-ablation AF recurrence has not been prospectively tested. TEAR-AF-HFpEF enrolls a population most likely to benefit mechanistically - obesity plus HFpEF - and tests the hypothesis with a hemodynamically defined HFpEF cohort.
Study Design: Multicenter randomized open-label parallel-group blinded-endpoint superiority trial. Eligible patients are randomized 1:1 within 48 hours of ablation, stratified by site, AF type (paroxysmal vs persistent), and BMI.
Intervention:
Tirzepatide arm: weekly subcutaneous tirzepatide starting at 2.5 mg/week with monthly 2.5 mg dose escalation to a target of 10 mg/week, advanced to 15 mg/week if tolerated, for 12 months.
Control arm: standard care without GLP-1 class drugs. Both arms receive identical structured lifestyle intervention (≥150 min/week moderate aerobic activity, sleep apnea screening), and standard-of-care guideline-directed therapies for AF, anticoagulation, and HFpEF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 80 years
- •Symptomatic atrial fibrillation (paroxysmal or persistent of ≤ 5 years duration), undergoing first-time catheter ablation
- •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)
- •HFpEF defined by intraprocedural mean left atrial pressure ≥ 15 mmHg at rest
- •Left ventricular ejection fraction ≥ 50% on echocardiography within 30 days prior to enrollment
- •Provision of written informed consent
排除标准
- •Prior use of any GLP-1 receptor agonist or GIP/GLP-1 dual receptor agonist
- •Type 1 diabetes mellitus; or type 2 diabetes with HbA1c > 10%
- •Personal history of pancreatitis; personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2)
- •Severe gastrointestinal disease, including gastroparesis or active inflammatory bowel disease
- •Prior bariatric surgery
- •Moderate or severe valvular heart disease, hypertrophic cardiomyopathy, cardiac amyloidosis, constrictive pericarditis, or restrictive cardiomyopathy
- •Severe renal impairment (eGFR < 30 mL/min/1.73m²)
- •Active malignancy, excluding basal cell carcinoma
- •Acute coronary syndrome, stroke, percutaneous coronary intervention, or cardiac surgery within 30 days prior to enrollment
- •Pregnancy, lactation, or planned pregnancy within 6 months
- •Life expectancy < 12 months
- •Concurrent participation in another interventional clinical trial
- •Any condition that, in the investigator's judgment, would interfere with participation
研究者
Yunlong Wang
Chief Physician; Professor;
Beijing Anzhen Hospital