Catheter Ablation vs Conservative Care in Elderly Patients With Atrial Fibrillation

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, Australia 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 age group (78-83 vs \>83 years).

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.

ILR implantation for continuous monitoring will be performed according to protocol-defined timing/workflow between the first and second visit.

Randomisation (1:1): central, concealed allocation; stratified by sex and age group (78-83 vs \>83 years).

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.

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 (two primary endpoints, tested with Holm-Bonferroni multiplicity control.)

The 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 RAND-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 RAND-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.

• Differences of atrial fibrillation and atrial tachycardia burden (ILR-derived) between groups [Time frame: From date of ILR implantation (intervention day, visit 2) up to 30 months after implantation.]
• Hospitalizations (all-cause and cardiovascular) [Time frame: Up to 24 months after intervention]
• Serious adverse events and treatment-related complications [Time frame: Up to 24 months after intervention]
• Additional patient-reported outcomes (AF symptoms / disease-specific HRQoL) [Time frame: Baseline and follow-up (3, 12, 18) through 24 months after intervention]
• Changes in Left atrial reservoir strain (LASr) [Time frame: Up to 12 months after intervention (visit 2)]
• Cognitive function measured by Montreal Cognitive Assessment (MoCA) [Time frame: MoCA scores will be collected and assessed at baseline, 12, 18, and 24 months after intervention (visit 2).]
• Frailty score assessed by e-Frailty index [Time frame: Up to 24 months after intervention; visit 2 ( 12, 18, and 24 months)]
• Discrimination of a prediction model for the ACE-AF primary composite outcome [Time frame: From baseline up to 24 months after intervention (visit 2).]
• Predictors of differential treatment effect on AF/AT burden [Time frame: From implantation (visit 2) up to 30 months after intervention]
• Participants with at least one event in the composite neurological endpoint (dementia, stroke, intracranial hemorrhage) [Time frame: Up to 24 months after intervention (visit 2).]
• Total healthcare costs per participant [Time frame: Up to 24 months after intervention (visit 2)]
• All-cause mortality, stroke/TIA, serious bleeding, cardiac arrest, hospitalization due to heart failure analyzed separately [Time frame: Up to 24 months after intervention]