Generalizability of the EAST-AFNET 4 Trial: Assessing Outcomes of Early RhythmControl Therapy in Patients With Atrial Fibrillation

Jannis Dickow, Paulus Kirchhof, Holly K. Van Houten, Lindsey R. Sangaralingham, Leon H.W. Dinshaw, Paul A. Friedman, Douglas L. Packer, Peter A. Noseworthy, Xiaoxi Yao

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BACKGROUND: EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) demonstrated clinical benefit of early rhythm-control therapy (ERC) in patients with new-onset atrial fibrillation (AF) and concomitant cardiovascular conditions compared with current guideline-based practice. This study aimed to evaluate the generalizability of EAST-AFNET 4 in routine practice. METHODS AND RESULTS: Using a US administrative database, we identified 109 739 patients with newly diagnosed AF during the enrollment period of EAST-AFNET 4. Patients were classified as either receiving ERC, using AF ablation or antiarrhythmic drug therapy, within the first year after AF diagnosis (n=27 106) or not receiving ERC (control group, n=82 633). After propensity score overlap weighting, Cox proportional hazards regression was used to compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction. Most patients (79 948 of 109 739; 72.9%) met the inclusion criteria for EAST-AFNET 4. ERC was associated with a reduced risk for the primary composite outcome (hazard ratio [HR], 0.85; 95% CI, 0.75– 0.97 [P=0.02]) with largely consistent results between eligible (HR, 0.89; 95% CI, 0.76–1.04 [P=0.14]) or ineligible (HR, 0.77; 95% CI, 0.60– 0.98 [P=0.04]) patients for EAST-AFNET 4 trial inclusion. ERC was associated with lower risk of stroke in the overall cohort and in trial-eligible patients. CONCLUSIONS: This analysis replicates the clinical benefit of ERC seen in EAST-AFNET 4. The results support adoption of ERC as part of the management of recently diagnosed AF in the United States.

Original languageEnglish (US)
Article numbere024214
JournalJournal of the American Heart Association
Issue number11
StatePublished - Jun 7 2022


  • antiarrhythmic drugs
  • atrial fibrillation
  • cather ablation
  • rhythm-control therapy
  • trial generalizability

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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