Initial Management of Atrial Fibrillation Without Ischemic Heart Disease: Class I OR Class III Antiarrhythmic therapy?

Document Type

Conference Proceeding

Publication Date

4-7-2026

Publication Title

Journal of the American College of Cardiology

Abstract

BACKGROUND Antiarrhythmic drugs (AADs) are commonly used as initial rhythm-control therapy in atrial fibrillation (AF). However, large-scale, head-to-head comparisons of Class I versus Class III agents as first-line treatment remain limited. METHODS We used TriNetX to identify adults diagnosed with AF in the absence of ischemic heart disease (IHD). Patients were categorized by first-line AAD use: Class I agents (flecainide, procainamide, propafenone) or Class III agents (amiodarone, sotalol, dofetilide). Patients who had catheter ablation were excluded. Five-year outcomes were all-cause mortality, all-cause hospitalization, heart failure (HF) hospitalization, ischemic stroke, and major bleeding (intracranial or gastrointestinal). RESULTS Among 239,328 eligible patients, 52,685 received Class I AAD (67.4 ± 11.6 years; 47.9% female) and 52,685 received Class III AAD (67.1 ± 12.9 years; 47.8% female) as first-line therapy after propensity score matching. Over five years of follow-up, Class I AAD was associated with a lower risk of all-cause mortality (6.1% vs. 12.0%, P< 0.01), all-cause hospitalization (34.3% vs. 42.7%, P< 0.01), HF hospitalization (9.1% vs. 15.5%, P< 0.01), and major bleeding (5.1% vs. 5.9%, P< 0.01) than Class III AAD. No difference was seen in ischemic stroke risk (7.2% vs. 6.2%, P=0.21). CONCLUSION In this five-year retrospective study, class I AAD was associated with better clinical outcomes than class III AAD as first-line therapy for AF among patients without IHD.

Volume

87

Issue

13 Suppl

First Page

A128

Comments

American College of Cardiology 75th Annual Scientific Session & Expo, March 28-30, 2026, New Orleans, LA

Last Page

A129

DOI

10.1016/j.jacc.2026.02.324

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