Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients : A Nationwide Propensity Score-Weighted Study

Ann Intern Med. 2022 Oct;175(10):1356-1365. doi: 10.7326/M21-4798. Epub 2022 Sep 6.


Background: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial).

Objective: To investigate whether the results can be generalized to patients with low stroke risk.

Design: Population-based cohort study.

Setting: Nationwide claims database of the Korean National Health Insurance Service.

Participants: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis.

Measurements: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting.

Results: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility.

Limitation: Residual confounding.

Conclusion: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility.

Primary funding source: The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents* / therapeutic use
  • Atrial Fibrillation* / drug therapy
  • Clinical Trials as Topic
  • Cohort Studies
  • Humans
  • Middle Aged
  • Propensity Score
  • Risk Assessment / methods
  • Risk Factors
  • Stroke / prevention & control


  • Anti-Arrhythmia Agents