The Clinical Safety and Efficacy of Sodium Channel Blocker Therapy for Rhythm Control in Atrial Fibrillation: Insights from the REGUEIFA Registry

<b>Background:</b> The aim of this study is to assess the safety of sodium channel blocker (SCB) therapy in patients with atrial fibrillation (AF). <b>Methods:</b> The REGUEIFA registry is a prospective, observational, multicenter registry from a Community Health Area in Spain that recruited patients with AF, whom it followed for 2 years. <b>Results:</b> From the 997 patients, 632 were assigned to a rhythm control strategy and analyzed. Patients exposed to SCBs demonstrated a risk ratio (RR) of 0.38 (95% CI: 0.18-0.79; <i>p</i> = 0.007) for worsening heart failure (HF), and 0.40 (95% CI: 0.21-0.78; <i>p</i> = 0.005) for the composite endpoint (death, ischemic stroke, or worsening HF), with no significant differences in all-cause mortality, cardiovascular (CV) mortality, ischemic stroke, or bleeding compared with patients not exposed to SCBs. In the subgroup of patients with structural heart disease, no differences were observed between those exposed and those not exposed to SCBs across all the clinical outcomes analyzed (all-cause mortality, CV mortality, ischemic stroke, bleeding and composite event). However, a lower event trend was observed across all these variables. The rate of sinus rhythm at 2 years follow-up was significantly higher in the SCB group (81.8% vs. 63.9%; <i>p</i> < 0.001). During Cox regression analysis for all-cause mortality, SCB exposure was not identified as an independent factor (HR: 0.82; 95% CI 0.17-3.87; <i>p</i> = 0.802). Age (HR: 1.10; 95% CI: 1.04-1.17; <i>p</i> < 0.001) and HF (HR: 4.23; 95% CI: 1.63-11.00; <i>p</i> = 0.003) were the only predictors of mortality. <b>Conclusions:</b> SCB therapy appears to be safe and effective, both in the overall cohort and in the patient subgroup with AF and structural heart disease. These agents may play a role in AF management in patients with revascularized coronary heart disease, left ventricular hypertrophy, and HF with preserved left ventricular ejection fraction.