Key result
Lamotrigine exposure was associated with an increased 1-year risk of incident atrial fibrillation compared to alternative agents in patients with bipolar disorder.
Why the study?
Lamotrigine has Class IB antiarrhythmic properties and FDA warnings for proarrhythmia in structural heart disease or myocardial ischemia, prompting evaluation of its association with AF.
Does lamotrigine increase the risk of atrial fibrillation in adult patients with bipolar disorder or seizures compared to alternative agents?
Cohort (n=407,352)
Does lamotrigine increase the risk of atrial fibrillation in adult patients with bipolar disorder or seizures compared to alternative agents?
Lamotrigine is associated with a significantly increased risk of incident atrial fibrillation compared to alternative agents in adults with bipolar disorder or partial seizures.
Answers are grounded in this paper and cite their sources.
May warrant AF monitoring with lamotrigine in bipolar disorder; leaves open causality and need for confirmatory trials.
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.
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Kim et al. (2024) conducted a cohort in Bipolar I disorder, partial seizures, or generalized tonic-clonic seizures (n=407,352). Lamotrigine vs. Commonly prescribed alternative agents was evaluated on 12 months cumulative incidence of atrial fibrillation (bipolar I disorder cohort) (HR 1.257, 95% CI 1.088-1.453). Lamotrigine exposure was associated with an increased 1-year risk of incident atrial fibrillation compared to alternative agents in patients with bipolar disorder.
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