Waiting on Atrial Fibrillation Intervention Therapy (WAIT) Study

Обзор

Atrial fibrillation (AF) is the most common heart rhythm disorder and is associated with symptoms, reduced quality of life, heart failure, stroke, and a high risk of recurrence after catheter ablation. Many patients scheduled for their first ablation are overweight or have obesity, which is one of the strongest predictors of AF recurrence. Weight loss and risk-factor management are known to improve the outcome of ablation, but lifestyle changes are often difficult to achieve in routine care. Semaglutide (Wegovy®) is a GLP-1 receptor agonist approved in the EU for weight management. It has been shown to produce substantial and sustained weight loss and to improve metabolic and cardiovascular risk factors. Whether treatment with semaglutide before AF ablation can improve long-term rhythm outcomes has never been tested in a randomized clinical trial. The WAIT-AF study is a randomized, open-label trial with blinded endpoint assessment. The study includes adults with AF who are scheduled for their first catheter ablation and have a BMI ≥30 kg/m², or ≥27 kg/m² with at least one additional cardiovascular risk factor (such as hypertension, diabetes and dyslipidemia). A total of 200 participants will be enrolled. Participants are randomly assigned in a 1:1 ratio to either standard care or semaglutide (plus lifestyle advice) prior to their scheduled ablation. Semaglutide is administered according to the approved EU label with gradual dose escalation. All participants receive an implantable loop recorder (ILR) before ablation to continuously monitor heart rhythm throughout the study. The primary objective is to determine whether semaglutide improves arrhythmia-free survival 12 months after AF ablation. Recurrence is defined as AF, atrial flutter, or atrial tachycardia lasting ≥30 seconds on continuous ILR monitoring, excluding the standard 3-month blanking period. Secondary outcomes include weight loss, changes in blood pressure, AF symptoms, quality of life, AF burden, need for repeat ablation, hospitalizations for cardiovascular causes, and changes in metabolic risk factors. The study also evaluates safety and tolerability of semaglutide in this patient population. The study aims to determine whether targeted weight management with semaglutide before AF ablation can improve long-term rhythm outcomes and overall cardiovascular health. If successful, this strategy may offer a new approach to optimizing treatment and improving the results of catheter ablation for patients with AF and overweight or obesity

Подробное описание

The WAIT trial evaluates whether metabolic optimization with once-weekly semaglutide prior to catheter ablation can improve rhythm outcomes in patients with atrial fibrillation and overweight/obesity. Excess adiposity and related cardiometabolic risk factors are strongly linked to atrial structural remodeling and higher rates of post-ablation arrhythmia recurrence. Although weight reduction is recommended in guidelines, sustained lifestyle-based weight loss is often difficult to achieve. Semaglutide provides an evidence-based pharmacologic strategy for clinically meaningful weight loss and risk-factor improvement, which may enhance the effectiveness of ablation.

This randomized, open-label study allocates participants 1:1 to semaglutide plus standard of care or standard of care alone for at least three months before undergoing their first AF ablation. All participants receive routine clinical management and continuous rhythm monitoring using an implantable loop recorder for 12 months post-ablation, with blinded adjudication of rhythm outcomes. The study integrates real-world clinical practice, using only routine clinical assessments, registry data, and ILR monitoring without introducing additional invasive procedures.

The trial is designed to determine whether targeted periablation metabolic therapy can increase arrhythmia-free survival, reduce AF burden, improve symptoms and quality of life, and favourably impact cardiovascular risk profiles. Results are expected to inform the role of GLP-1 receptor agonist therapy as part of a structured periablation optimization strategy for patients with AF and overweight or obesity.

Вмешательства

• Препарат Semaglutide 2.4 mg
  The intervention consists of once-weekly subcutaneous semaglutide (Wegovy®), initiated at 0.25 mg and uptitrated to a target dose of 2.4 mg as tolerated, administered for at least three months prior to the participant's first planned atrial fibrillation ablation. Semaglutide is provided in pre-filled pens and used according to the approved SmPC for weight management. This intervention is uniquely characterized by pharmacological weight-loss therapy added on top of standard-of-care management, di
• Поведенческое Standard medical treatment
  Participants randomized to the standard-of-care arm receive routine clinical management for atrial fibrillation and weight-related comorbidities without GLP-1 receptor agonist therapy. Usual care may include lifestyle counselling, blood pressure and lipid management, treatment of dysglycaemia, and guideline-directed preparation for first-time catheter ablation. No trial-specific medicinal product is administered.

Первичные конечные точки

• Arrhythmia-free survival at 12 months after catheter ablation, excluding the 3-month blanking period, with recurrence defined as any ILR-detected AF, atrial flutter, or atrial tachycardia ≥30 seconds. [Срок оценки: 12 months post-ablation]

Вторичные конечные точки (12)

• AF burden [Срок оценки: At ablation and at 12 months post-ablation.]
• Per protocol analysis of the primary outcome [Срок оценки: 12 months post-ablation]
• Time to first arrhythmia recurrence after the blanking period [Срок оценки: From month 3 to month 12 post-ablation.]
• Number of repeat ablations required to achieve sinus rhythm [Срок оценки: From index ablation to 12 months post-ablation.]
• Freedom from symptomatic AF without redo ablation [Срок оценки: From index ablation to 12 months post-ablation.]
• Symptom burden using questionnaires at baseline, ablation, 12 months [Срок оценки: At baseline, at the time of ablation, and at 12 months post-ablation]
• Quality of life changes using RAND-36 [Срок оценки: At baseline, at the time of ablation, and at 12 months post-ablation.]
• Weight loss ≥10% or BMI <27 kg/m² at time of ablation and at 12 months post ablation [Срок оценки: At the time of ablation and at 12 months post-ablation.]
• Blood pressure reduction [Срок оценки: At baseline, at the time of ablation, and at 12 months post-ablation.]
• Changes in blood biomarkers including glucose levels, HbA1c, creatinine and NT-proBNP [Срок оценки: At routine clinical assessments nearest to baseline, ablation, and 12 months post-ablation.]
• Complications during and after the ablation procedure [Срок оценки: During the ablation procedure and through 12 months post ablation.]
• Left ventricular ejection fraction (LV-EF) pre- and post-ablation [Срок оценки: At routine clinical echocardiography closest to baseline and the post-ablation assessment (up to 12 months).]

Критерии участия

Критерии включения

To be included in the trial, subjects must meet all of the following criteria:

• Provision of written informed consent prior to participation.
• Age ≥18 years.
• Scheduled for first-time catheter ablation for atrial fibrillation using a pulmonary vein isolation (PVI) technique.
• Body Mass Index (BMI) ≥30 kg/m² (obesity) OR

BMI ≥27 kg/m² (overweight) with one or more of the following comorbidities:

• prediabetes (defined as HbA1c 39-47 mmol/mol or fasting glucose 5,6-6,9 mmol/L),
• known diabetes type 2
• known hypertension (prior diagnosis and/or treatment with antihypertensive medication)
• new diagnosis of hypertension (according to ESC GL for hypertension: Systolic BP ≥140 mmHg and/or diastolic BP ≥ 90 mmHg based on two readings on two separate visits, OR Ambulatory BP monitoring (24h average) ≥ 130/80 mmHg)
• dyslipidemia defined as either one of the following

• Known diagnosis of hyperlipidemia or
• Treatment with lipid lowering medication

OR either of the following:

• LDL > 3.0 mmol/l
• Total cholesterol > 5 mmol/l
• Triglycerides > 1.7 mmol/l
• HDL (< 1 mmol/l if male, < 1.2 mmol/l if female) AND/OR

• atherosclerotic cardiovascular disease (prior myocardial infarction (MI), stroke, or peripheral arterial disease with claudication and ankle-brachial index <0.85, prior revascularization, or amputation)
• obstructive sleep apnea.
• For women of childbearing potential: Inclusion after a highly sensitive negative pregnancy test and agreement to use highly effective contraception during the study period (e.g., hormonal contraception, intrauterine device, or barrier method combined with spermicide).

Критерии исключения

• Morbid obesity (BMI >40 kg/m²).
• Current use of GLP-1 receptor agonist therapy or dual agonist therapy within 6 months before screening.
• Current use of DPP-IV inhibitors.
• Diabetes type 1
• Known intolerance or contraindication to semaglutide.
• History of pancreatitis or recurrent hypoglycemia.
• Uncontrolled diabetic retinopathy
• Severe renal failure (estimated glomerular filtration rate \[eGFR\] <15 mL/min/1.73 m² or in dialysis)
• Severe hepatic failure (decompensated liver disease Child-Pugh class C)
• Severe cardiac failure (NYHA class IV)
• Life expectancy <12 months.
• Inability to self-administer the investigational medicinal product.
• Prior catheter ablation procedure for atrial fibrillation.
• Pregnancy, breastfeeding, or planned pregnancy during or within two months after the study period.
• Participation in another interventional clinical trial within the past 30 days.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Швеция · 1 центр

• Karolinska University Hospital — Stockholm

Идентификаторы

NCT: NCT07275697 · WAIT · 2025-524182-25-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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