Association of atrial fibrillation with lamotrigine: An observational cohort study

Abstract

Background: Drug-induced atrial fibrillation (AF) is recognized as an important causal association. Lamotrigine (LTG) is a widely prescribed neurological agent with Class IB antiarrhythmic properties at therapeutically relevant concentrations. The United States Food and Drug Administration has issued a warning for a higher risk of LTG proarrhythmic events in patients with structural heart disease (SHD) and/or myocardial ischemia. This study evaluated the incidence of AF with LTG use.

Methods: A retrospective observational study was performed using a large healthcare claims database of adult participants analyzing 2 years AF incidence. The analytic cohort included adult participants with bipolar I disorder (BPD), partial seizures (PSZ), or generalized tonic-clonic seizures (GTSZ). Exposure to LTG was compared with commonly prescribed alternative agents as the control comparators (CTR). Participants were free from supraventricular or ventricular arrhythmias during the 6 months baseline period prior to the index LTG or CTR date. Kaplan-Meier estimator calculated 2 years cumulative AF incidence, with participants censored at last enrollment, treatment switching, or discontinuation. The AF association hazard ratios (HR) for LTG versus CTR were adjusted for baseline characteristics.

Results: The analytic cohort with BPD, PSZ, and GTSZ consisted, respectively, of 150,470 LTG versus 204,704 CTR, 9565 LTG versus 21,595 CTR, and 5505 LTG versus 15,513 CTR patients. In a predominantly middle-aged female population at baseline, the prevalence of cardiovascular conditions was low. The 12 months cumulative incidence of AF for LTG versus CTR was 0.764% versus 0.642% among BPD, 0.833% versus 0.646% among PSZ, and 0.585% versus 0.338% among GTSZ, respectively. The adjusted 365-day HR [95% confidence interval CI] of AF for LTG versus CTR in the BPD, PSZ, and CTSZ groups was 1.257 [1.088-1.453], 1.651 [1.104-2.468], and 1.451 [0.770-2.734], respectively.

Conclusions: In adult AF-naïve participants, LTG has a strong association with increased AF risk compared with commonly prescribed alternatives.

Keywords: atrial fibrillation; bipolar I disorder; generalized tonic–clonic seizures; lamotrigine; observation cohort study; partial seizures.