Abstracts

Rationale: The US Food and Drug Administration recently issued a warning against the use of the antiseizure medication lamotrigine in people at risk of cardiac rhythm and conduction abnormalities. This study assesses the risk of cardiac morbidity and mortality in new users of lamotrigine.

Methods: We conducted a population-based cohort study of patients aged ≥15 years who initiated lamotrigine treatment in Denmark between January 1, 1997 and December 31, 2016. Lamotrigine users were identified using the Danish National Prescription Register.

Information on cardiac morbidity in cohort members was obtained from the Danish National Patient Register and all-cause mortality from the Danish Registry of Causes of Death.

The main outcomes of interest in the present study were risk of cardiac conduction disorders, which was defined as a composite outcome of pacemaker implantation, advanced second- or third-degree atrioventricular block, or sinoatrial dysfunction in people without pre-existing cardiac morbidity, and all-cause mortality in people with pre-existing cardiac morbidity.

We estimated incidence rates (IR) and corresponding 95% confidence intervals (CIs), and used Cox Proportional Hazard models to obtain hazard ratios (HRs) adjusted for sex, age at lamotrigine initiation, and calendar year at time of lamotrigine initiation. HRs compared the risk of current treatment with lamotrigine compared to past treatment, where lamotrigine treatment was included as time-varying exposure in the first two years after initiation of lamotrigine therapy. Persons were followed from time of lamotrigine initiation until time of cardiac outcome, death, emigration, or end of follow-up (31 December 2016).

Results: We identified 91,949 persons who reimbursed their first prescription for lamotrigine between 1997 and 2016.

There were 86,769 users of lamotrigine without pre-existing cardiac disease and 5,180 users of lamotrigine with pre-existing cardiac disease.

Among the users without pre-existing cardiac disease, 194 (0.23%) developed a cardiac conduction disorder in the first two years after lamotrigine initiation. The adjusted HR of new onset cardiac conduction disorders was 1.02 (95% CI: 0.75 – 1.39) in users of lamotrigine without pre-existing cardiac disease.

Among the users with pre-existing cardiac disease, 1150 (22.2%) died in the first two years after lamotrigine initiation. The adjusted HR of all cause-mortality in users of lamotrigine with pre-existing cardiac disease was 0.90 (95% CI: 0.79 – 1.03).

Conclusions: In this large population-based study, use of lamotrigine was not associated with risk of cardiac conduction disorders in people without pre-existing cardiac morbidity, and the use of lamotrigine was not associated with all-cause mortality in people with pre-existing cardiac morbidity.

Funding: Please list any funding that was received in support of this abstract.: The study was supported by the Danish Epilepsy Association, the Central Denmark Region, and the Novo Nordisk Foundation (NNF16OC0019126).