NCT07424690

Catheter Ablation vs Conservative Care in Elderly Patients With Atrial Fibrillation

Assessment of the Effect of Catheter Ablation on Elderly Population With Atrial Fibrillation; a Randomized Controlled Study; The ACE-AF Study

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 282 (estimated)
• Sponsor: Karolinska University Hospital · Academic / Other
• Sex: All
• Age: 78 Years
• Healthy volunteers: Not accepted

Summary

ACE-AF is a multicenter randomized study in people aged 78 years and older with symptomatic atrial fibrillation (AF). AF is a common heart rhythm disorder in older adults and can cause reduced quality of life and lead to serious complications such as stroke and heart failure. The study compares two established treatment strategies: 1. Catheter ablation (an invasive procedure aimed at reducing AF by electrically isolating triggers in the heart, primarily through pulmonary vein isolation), and 2. Optimized medical therapy without AF ablation (medications for rate and/or rhythm control; AV node ablation with pacemaker may be used if clinically indicated according to routine care). Participants are randomized 1:1 to one of these strategies. All participants will receive an implantable loop recorder (a small heart rhythm monitor placed under the skin) to continuously track heart rhythm and measure AF burden over time. The study has two co-primary outcomes assessed over 24 months: 1. a composite of major clinical events (all-cause mortality, stroke, major bleeding, cardiac arrest, or hospitalization due to heart failure), and 2. patient-reported health-related quality of life (HRQoL), measured by the SF-36 "General Health" domain. ACE-AF will provide evidence to guide treatment decisions for very elderly patients with symptomatic AF and help identify which patients benefit most from an ablation-based strategy compared with optimized medical therapy.

Detailed description

Background and Rationale Atrial fibrillation (AF) is highly prevalent in very elderly individuals and is associated with substantial morbidity, including stroke, heart failure (HF), recurrent hospitalisations, polypharmacy, frailty, and impaired health-related quality of life (HRQoL). Catheter ablation is an established rhythm-control therapy in AF, but patients aged ≥78 years have been under-represented in randomised trials, and evidence on comparative effectiveness and safety versus optimised medical therapy in this age group remains limited. ACE-AF is designed to address this knowledge gap using a pragmatic randomised strategy design and continuous rhythm monitoring in both arms. Study Design ACE-AF is an investigator-initiated, multicentre, parallel-group, open-label randomised controlled trial conducted at seven Swedish university hospitals and collaborating centres in Denmark and Greece. Participants aged ≥78 years with symptomatic paroxysmal or persistent AF are randomised 1:1 to an ablation-based strategy or to optimised medical therapy without AF ablation. Randomisation is performed centrally using an electronic system with allocation concealment until assignment, stratified by sex and Charlson comorbidity index. Study Arms and Interventions Arm A: Catheter ablation strategy Catheter ablation is performed according to contemporary clinical practice at experienced centres. Pulmonary vein isolation (PVI) is prioritised as the primary ablation strategy. Energy source and tools are selected according to local practice and operator discretion, without restriction to a specific technology. Periprocedural management (imaging, anticoagulation, anaesthesia strategy) follows local standards of care and the study protocol. Arm B: Optimised medical therapy strategy (no AF ablation) Guideline-directed rate and/or rhythm control tailored to clinical need, including antiarrhythmic drugs and/or cardioversion when appropriate. AV-node ablation with pacemaker implantation is permitted when clinically indicated, according to standard care. Treatment optimisation and follow-up adhere to protocol-defined principles and local clinical routines. Rhythm monitoring (both arms) All participants receive an implantable loop recorder (ILR) to enable continuous rhythm monitoring, including quantification of AF burden and detection of clinically relevant arrhythmias over time (ILR programming per protocol). Study Flow and Follow-up Screening/Baseline (pre-randomisation/visit 1): informed consent; baseline clinical assessment including comorbidity profiling; baseline questionnaires and planned assessments per protocol. Randomisation (1:1): central, concealed allocation; stratified by sex and Charlson comorbidity index. Intervention phase (visit 2): Ablation arm: catheter ablation performed as per protocol and site standards. Control arm: initiation/optimisation of medical therapy; AV-node ablation with pacing permitted if clinically indicated. ILR implantation for continuous monitoring according to protocol-defined timing/workflow. Follow-up visits: scheduled follow-up visits are performed at approximately 3, 12, 18 and 24 months after randomisation/intervention, with continuous ILR surveillance throughout follow-up. At follow-up, clinical events, adverse events, treatment changes, and patient-reported outcomes are collected according to protocol, and ILR rhythm summaries are reviewed. Primary Outcomes (co-primary; multiplicity controlled) Co-primary endpoints are evaluated over 24 months after randomisation and controlled for multiplicity using the Holm-Bonferroni procedure: Composite clinical endpoint: all-cause mortality, stroke, serious bleeding, cardiac arrest, or hospitalisation due to heart failure within 24 months after randomisation. HRQoL endpoint: effect on HRQoL measured by the SF-36 "General Health" domain. Secondary Outcomes Secondary outcomes include (as specified in the protocol): AF burden and rhythm outcomes (ILR-derived): AF burden over time, recurrence patterns, and detection of clinically relevant rhythm events. Healthcare utilisation: hospitalisations and AF/HF-related care contacts. Patient-reported outcomes: symptom burden and HRQoL using validated instruments (including SF-36 and additional AF-related questionnaires per protocol). Safety outcomes: procedure-related and treatment-related complications and serious adverse events. Treatment pathways: need for cardioversion, medication escalation, AV-node ablation with pacing, and crossover patterns (as applicable). Exploratory Objectives and Planned Subgroup/Modifier Analyses Exploratory analyses will examine whether treatment effects differ by baseline characteristics and geriatric domains, including: Frailty (e.g., Frailty Index and/or Clinical Frailty Scale). Cognitive status (protocol-defined assessment). Inflammatory biomarkers and overall comorbidity burden. Sex (sex-disaggregated reporting and interaction analyses). AF type (paroxysmal vs persistent). Imaging substudy (selected Swedish sites): a predefined subgroup (e.g., at Karolinska and Linköping) planned for brain and/or cardiac imaging with MRI and/or CT per protocol to explore mechanistic associations. Saliva sampling (optional subgroup): in a predefined subgroup, saliva is collected for exploratory biomarker/genetic analyses relevant to ageing and treatment response (separate consent; optional participation). If subgroup analyses are underpowered, results will be reported as exploratory. Sample Size and Statistical Considerations The planned sample size is 282 participants, providing adequate power to detect clinically meaningful differences over 24 months, accounting for crossover and loss to follow-up. Primary analyses are performed according to the intention-to-treat principle. Multiplicity across the co-primary endpoints is addressed using a pre-specified Holm-Bonferroni approach. Safety Oversight Participant safety is overseen by an independent Data Monitoring Committee (DMC), comprising senior cardiology researchers independent of the study (Professor Eva Swahn, Professor Lars Lund, and Professor Johan Engdahl). Safety monitoring and adverse event reporting are conducted throughout the study according to the protocol. Ethics, Regulatory, and Data Protection The study has been approved by the Swedish Ethical Review Authority (Dnr 2025-02305-01; decision date 12 May 2025). Data are pseudonymised and processed in compliance with GDPR, with data captured in an electronic CRF (REDCap).

Conditions

• Atrial Fibrillation (AF)
• Atrial Fibrillation Ablation
• Elderly

Interventions

Type	Name	Description
PROCEDURE	Catheter Ablation for Atrial Fibrillation	Catheter ablation for symptomatic atrial fibrillation with pulmonary vein isolation (PVI) prioritized as the primary lesion set. Energy source and tools are selected according to local practice and operator discretion (no restriction to a specific technology), performed under routine standards of care at experienced centres.
DRUG	Optimized Medical Therapy for Atrial Fibrillation	Guideline-directed rate and/or rhythm control tailored to the participant's clinical condition, including rate-control medications and/or antiarrhythmic drugs and cardioversion when clinically appropriate. AF ablation is not performed as part of this strategy.
DEVICE	Implantable Loop Recorder (ILR)	Subcutaneous implantable loop recorder used for continuous rhythm monitoring and quantification of atrial fibrillation burden throughout follow-up. Implanted in all participants according to protocol-defined workflow.
PROCEDURE	AV Node Ablation With Pacemaker implantation	AV node ablation with permanent pacing may be performed when clinically indicated according to routine care, as part of the optimized medical therapy strategy.

Timeline

• Start date: 2026-05-20
• Primary completion: 2031-11-01
• Completion: 2034-09-01
• First posted: 2026-02-20
• Last updated: 2026-02-20

Locations

1 site across 1 country: Sweden