Abstract Body (Do not enter title and authors here): Objective: Atrial fibrillation (AF) is the most common arrhythmia with the incidence and prevalence increasing worldwide. Lamotrigine (L) is a widely prescribed medication for Bipolar I disorder (BPI). L reduces intracellular sodium through inhibition of the voltage-gated sodium channels which slows cardiac conduction velocity. The mechanism can lead to an onset of AF. The aim of this study was to examine the incidence of AF in L patients without a history of cardiac arrhythmias or structural heart disease (SHD) vs controls prescribed common medications for BPI.

Methods: We identified adult patients with BPI who received L or control agents (C) including lithium, quetiapine, valproate, and risperidone from Merative MarketScan^® Commercial Claims and Medicare Supplemental Database. Patients were naive from AF at least six months prior to receiving L or C. Onset of AF was determined using ICD 9 and 10 codes. Patients were censored for generating the Kaplan-Meier cumulative incidence if switched between L and C, discontinued L or C during follow-up, end of continuous enrollment or end of one-year follow up. Onset of AF on L versus C was compared using hazard ratio (HR) calculated from a multivariable Cox-proportional hazard regression model. As a sensitivity analysis, we performed an analysis using a propensity score matched cohort.

Results: The BPI cohort consisted of 150,470 L vs. 204,704 C patients with 145,467 pairs for PSM. The 1-year cumulative incidence of AF from L and C was 0.764% and 0.642%, respectively, calculating a HR of 1.257 [95% CI: 1.0878-1.4534], p=0.0019. (Figure 1). The number of patients needed for one AF incidence/year is 820. Results from the sensitivity analysis were very similar.

Conclusions: In adult naïve AF patients, L compared to C taking commonly prescribed BPI medications was associated with a higher risk of AF.