EAST AFNET 4 Trial: Early Rhythm control in Atrial Fibrillation

EAST AFNET Trial: Afib

In patients with nonvalvular afib, rate control was considered to be no different than rhythm control based on the AFFIRM trial results that was published in 2002. Fast forward 18 years, the EAST-AFNET 4 trial has revisited the question of rhythm control in afib.

Clinical Question:

The EAST AFNET 4 trial evaluated if early rhythm-control therapy can reduce cardiovascular risk in patients who had recent atrial fibrillation (diagnosed ≤1 year before enrollment).

Bottom Line:

The trial had significantly positive results in favor of rhythm control. Early rhythm-control therapy was associated with a lower risk of cardiovascular outcomes than usual care among patients with atrial fibrillation and cardiovascular conditions.

Trial Design:

Parallel-group, open, blinded-outcome-assessment trial


In total, 2789 patients were included and were randomized to early rhythm
control (N=1395) or usual care (N=1394).

Inclusion Criteria:

  • Recent AF (AF diagnosed within 1 year) and >75 years of age and had a previous TIA or stroke, OR
  • Met two of the following criteria: age >65 years, female sex, heart failure (HF), hypertension, diabetes mellitus, severe coronary artery disease, chronic kidney disease, left ventricular hypertrophy (diastolic septal wall width >15 mm)

Primary Outcomes:

  1. CV death, stroke, or hospitalization with heart failure or ACS

3.9% patients in the rhythm control group had primary endpoint event compared to 5% in the usual care group. HR 0.79; 96% CI 0.66 to 0.94; P=0.005

2. Nights spent in hospital/yr

5.8 nights average in rhythm control group compared with 5.1 in usual care. HR 1.08; 99% CI, 0.92 to 1.28; P=0.23

Key Secondary Outcomes:

1. Serious adverse events related to rhythm-control therapy

4.9% patients had a serious adverse event in rhythm control group compared with 1.4% in usual care. HR 1.73; 95% CI, 1.10 to 2.37; P<0.001

Take Home Point:

The usual care mostly included rate controlled and based on the EAST AFNET, rhythm control was noted to be superior in terms of cardiovascular outcomes. Results of this trial are different from other similar trials such as CABANA-AF, AFFIRM, and RACE which is likely due to the fact that patients with recent AF (within 1 year dx) were included.

Ref: Kirchhof et al. N Engl J Med 2020;Aug 29

In Depth Analysis: EAST AFNET 4 Trial

The RACE and AFFIRM trials were published in 2002. The key objective of those trials was to assess if rate control strategy was noninferior to rhythm control strategy in afib. Antiarrythmic drugs carry significantly more side effects when compared to rate controlling agents such as beta blockers and calcium channel blockers. For past 18 years, most patients with afib have been rate controlled especially if they are asymptomatic. Patients with symptomatic afib usually undergo cardioversion with or without TEE to based on their anticoagulation use. While other patients are candidates for afib ablation. The RACE and AFFIRM trials included patients who had recurrent and persistent AF and therefore had higher chance of failing antiarrythmic therapy.

The EAST AFNET 4 trial has answered a very important question as to what should be done in patients who comes in with recently diagnosed afib. One year afib history actually improves the results even further as the trial was able to screen and recruit almost 3000 patients. The AFFIRM trial was designed to test all-cause mortality and was not powered towards its secondary outcomes however it included 4000 patients. There was no mortality difference in either group in that trial nor was there any difference in ischemic stroke events. The authors did note difference in hospitalization rates with more hospitalization in the rhythm control group. Similar to that the RACE trial was powered to test CV outcomes in patients with recurrent AF but included only ~600 patients.

The EAST AFNET 4 trial might definitely be practice changing as it shows favorable results for those who underwent rhythm control early on in their afib course. The driving factors of the composite outcome were reduced CV mortality [ HR 0.72 (0.52 to 0.98) ]and reduced no. of strokes [ 0.65 (0.44 to 0.97] in favor of rhythm control. Per the authors, the probable reason for this difference was more utility of afib ablation in addition to antiarrythmics and rate controlling agents in the antiarrythmic group.

This is not the first time that early rhythm control strategy has shown improvement of outcomes. In the ATHENA study, dronedarone showed to improve CV mortality as well as stroke risk in post hoc analysis when compared to placebo. In that study 68% of patients enrolled had afib occurrence within 1 year. With the EAST AFNET 4 results, electrophysiologists will probably be more comfortable in offering AF ablation option to patients.