EASThigh-AFNET 11 is an international, prospective, randomized, open, blinded endpoint assessment, multicenter trial (Treatment Strategy trial).

The objective of EASThigh-AFNET 11 is to investigate whether early atrial fibrillation ablation in patients with atrial fibrillation (AF) and a high comorbidity burden (CHA2DS2-VASc ≥4) reduces cardiovascular events (stroke, cardiovascular death, or heart failure events) compared to usual care.

Atrial Fibrillation (AF) is associated with high morbidity and mortality. Even on optimal anticoagulation and therapy of concomitant conditions, many patients with AF suffer cardiovascular events, especially heart failure events, stroke, and cardiovascular death. Most of these events occur in elderly patients with comorbidities. Early rhythm control, mainly delivered using antiarrhythmic drugs, reduces AF-related complications when added to anticoagulation, rate control, and treatment of comorbidities when compared to current practice that offers rhythm control mainly to reduce symptoms. The outcome-reducing effect of early rhythm control is most pronounced in patients with multiple comorbidities, quantified by a CHA2DS2-VASc score ≥ 4. Attaining sinus rhythm is the key mediator for the outcome-reducing effect of early rhythm control. Atrial fibrillation ablation controls the rhythm better than drug-based rhythm control, avoids long-term antiarrhythmic drug treatment, thus reducing polypharmacy, and may therefore be the ideal rhythm control treatment in patients with AF and a high comorbidity burden. This hypothesis needs testing. The investigator-initiated EASThigh-AFNET 11 trial evaluates the effectiveness and safety of early atrial fibrillation ablation in patients with recently diagnosed AF and a high comorbidity burden.

EASThigh-AFNET 11 is a Treatment Strategy trial randomizing 2312 patients with AF and a high comorbidity burden to early atrial fibrillation ablation or usual care to achieve a fixed number of primary endpoint events of n=527. All therapies are clinically approved. The primary outcome is a composite of cardiovascular death, stroke, and hospitalization for worsening of heart failure. The primary safety outcome is a composite of all-cause death and serious complications of AF therapy. Secondary outcome parameters address safety, patient reported outcomes and cognitive function.

EASThigh-AFNET 11 was recommended for funding by the Expert Advisory Panel of the Global Cardiovascular Research Funders Forum (GCRFF).

Inclusion Criteria:

I1. AF first diagnosed within 5 years prior to enrolment and documented in body surface ECG

I2. High comorbidity estimated by CHA2DS2-VASc score of 4 or more

I3. Patient suitable for ablation using cryoballoon ablation systems or other ablation systems with comparable efficacy and safety from Medtronic

I4. Age ≥ 18 years

I5. Provision of signed informed consent

Exclusion Criteria:

General exclusion criteria

E1. Any disease that limits life expectancy to less than 1 year.

E2. Participation in another clinical trial, either within the 3 months prior to enrolment or still on-going (participation in potential sub-studies connected to this trial is permitted).

E3. Previous participation in EASThigh-AFNET 11.

E4. Pregnant women.

E5. Breastfeeding women.

E6. Drug abuse or clinically manifest alcohol abuse.

Exclusion criteria related to a cardiac condition

E7. Prior AF ablation or surgical therapy of AF.

E8. Patients not suitable for AF ablation.

E9. Patients with a history of stroke which occurred within 3 months prior to enrolment.

E10. Valve disease requiring specific therapy.

Exclusion criteria based on laboratory abnormalities

E11. Clinically manifested thyroid dysfunction requiring therapy.

blinded endpoint assessment