Long-Term Outcomes With Class 1C Antiarrhythmic Drug Use in Atrial Fibrillation

Rhythm control with class 1C antiarrhythmic drugs (AADs) is a widely used treatment among patients with atrial fibrillation (AF), but cardiovascular benefits of class 1C pharmacotherapy over rate control strategy are still unclear.

Adult patients with AF (n=100 748; 45% women) evaluated at a multihospital health system between 2010 and 2023 were assessed on clinical characteristics and class 1C AAD use and long-term outcomes ascertained. Covariate balance across 36 factors was achieved using propensity score matching. Adjusted Cox modeling with competing risk analysis was used to compare patients using rhythm control (class 1C) with those offered a rate control strategy.

Patients receiving a class 1C AAD (n=5239 [5%]) (70% flecainide) were significantly younger with lower cardiovascular risk factors (hypertension, diabetes, coronary artery disease, heart failure) and less comorbidity burden. Over a mean follow-up of 5±3 years, matched patients receiving a class 1C AAD had significantly less all-cause death (14% versus 19%; hazard ratio [HR], 0.65 [95% CI, 0.57-0.74]; P<0.001). Age (P=0.017), CHA₂DS₂-VASc score (P=0.0003), and comorbidity burden (P=0.032) modify this relationship, while prior revascularization (P=0.83) or presence of coronary artery disease had no significant (P=0.54) impact. Class 1C recipients also had lower stroke hospitalization (3.6% versus 4.8%; HR, 0.82 [95% CI, 0.8-0.95]; P=0.01), while those aged 65 to 80 years experienced less heart failure (HR, 0.84 [95% CI, 0.71-0.98]; P=0.03) and major bleeding (HR, 0.8 [95% CI, 0.65-0.98]; P=0.039) as well.

In a real-world contemporary registry of patients with AF from a North American health care system, use of class 1C AADs for rhythm control was associated with improved survival and hospitalization for stroke compared with rate control.