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JACC Clin Electrophysiol. 2019 Feb;5(2):231-241. doi: 10.1016/j.jacep.2018.08.025. Epub 2018 Nov 1.

Real-World Comparison of Classes IC and III Antiarrhythmic Drugs as an Initial Rhythm Control Strategy in Newly Diagnosed Atrial Fibrillation: From the TREAT-AF Study.

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Division of Cardiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Division of Cardiology, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina; Division of Cardiology, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina.
Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Department of Medicine, Stanford University School of Medicine, Stanford, California; Center for Digital Health, Stanford University School of Medicine, Stanford, California. Electronic address:



In this study the authors investigated effectiveness and safety of an initial treatment strategy with class IC or class III antiarrhythmic drugs (AAD) for newly diagnosed atrial fibrillation (AF) or atrial flutter (AFL).


There is limited evidence to guide optimal AAD selection for rhythm control in newly diagnosed AF/AFL.


Using data from TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF), the authors performed a retrospective cohort study of patients with AF/AFL from 2004 to 2014 and class IC or class III AAD prescription within 90 days following diagnosis. Patients with prior myocardial infarction, heart failure, or end-stage renal disease were excluded. Inverse probability treatment weighted propensity scores were used to evaluate the association of AAD class on hospitalization and cardiovascular events. To evaluate residual confounding, falsification outcomes were evaluated.


A total of 230,762 patients developed newly diagnosed AF/AFL during the study period. Of those, 3,973 patients (1.7%) were prescribed class IC and 6,909 (3.0%) were prescribed class III AAD. Median follow-up was 4.9 years. After inverse probability treatment weighted adjustment, class IC medications were associated with lower risk of hospitalizations for AF/AFL (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.73 to 0.81), cardiovascular disease (HR: 0.78; 95% CI: 0.75 to 0.81), heart failure (HR: 0.70; 95% CI: 0.64 to 0.76), and lower incidence of ischemic stroke (HR: 0.74; 95% CI: 0.65 to 0.85). Similar results were found in CHADS2 (Congestive Heart Failure, Hypertension, Age ≥75 Years, Diabetes Mellitus, Prior Stroke, Transient Ischemic Attack, or Thromboembolism) 0 or 1 and CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age ≥75 Years, Diabetes Mellitus, Prior Stroke, Transient Ischemic Attack, or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) 0 or 1 subgroups. Falsification analyses for outcomes of urinary tract infection, pneumonia, and hip fracture were generally nonsignificant.


Prescription of class IC AAD as initial treatment for newly diagnosed AF/AFL, compared with prescription of class III AAD, may be associated with lower risk of hospitalization and cardiovascular events.


antiarrhythmic medication; atrial fibrillation; heart failure; hospitalization

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