Cardiac morbidity and mortality associated with the use of lamotrigine
Jakob Christensen1,2, Betina B Trabjerg1,3, Julie Werenberg Dreier1,3
1National Center for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark.
Insights
Lamotrigine, an antiseizure drug, does not appear to increase cardiac risks. This study found no link between lamotrigine use and cardiac conduction disorders or all-cause mortality in new users.
Area of Science:
- Cardiology
- Pharmacology
- Neurology
Background:
- The US FDA issued a warning regarding lamotrigine's potential cardiac risks.
- Lamotrigine is an antiseizure medication used for epilepsy and bipolar disorder.
Purpose of the Study:
- To assess the risk of cardiac morbidity and mortality in new users of lamotrigine.
- To investigate lamotrigine's association with cardiac conduction disorders and all-cause mortality.
Main Methods:
- A Danish population-based cohort study followed new lamotrigine users (≥15 years) for 2 years.
- Cox proportional hazards models were used to analyze cardiac conduction disorders and all-cause mortality.
- Outcomes included cardiac conduction disorders in those without pre-existing cardiac conditions and all-cause mortality in those with pre-existing conditions.
Main Results:
- The study included 91,949 new lamotrigine users.
- No significant association was found between lamotrigine use and new-onset cardiac conduction disorders (adjusted HR: 1.03; 95% CI: 0.76-1.40).
- No significant association was found between lamotrigine use and all-cause mortality in patients with pre-existing cardiac disease (adjusted HR: 1.05; 95% CI: 0.93-1.19).
Conclusions:
- Lamotrigine use was not associated with an increased risk of cardiac conduction disorders in individuals without pre-existing cardiac morbidity.
- Lamotrigine use was not associated with an increased risk of all-cause mortality in individuals with pre-existing cardiac morbidity.
Objective:
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 assessed the risk of cardiac morbidity and mortality in new users of lamotrigine.
Methods:
In a Danish population-based cohort study, we followed cohort members aged ≥15 years for the first 2 years after they initiated lamotrigine therapy. The main outcomes were cardiac conduction disorders in people without pre-existing cardiac morbidity and all-cause mortality in people with pre-existing cardiac morbidity. Cox proportional hazards models provided hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for comparison of the risk in current versus past users of lamotrigine.
Results:
There were 91 949 (36 618 males [39.8%]) new users of lamotrigine (median age = 45.7 years, interquartile range = 32.0-60.2 years). Among users without pre-existing cardiac disease (n = 86 769), 194 (.23%) developed a cardiac conduction disorder. Comparison of the risk in current and past lamotrigine treatment periods yielded an adjusted HR of new onset cardiac conduction disorder of 1.03 (95% CI = .76-1.40). Among users with pre-existing cardiac disease (n = 5180), 1150 (22.2%) died. Comparison of the risk in current and past lamotrigine treatment periods yielded an adjusted HR for all cause-mortality of 1.05 (95% CI = .93-1.19).
Significance:
In this large population-based study, lamotrigine use was associated neither with a risk of cardiac conduction disorders in people without pre-existing cardiac morbidity nor with all-cause mortality in people with pre-existing cardiac morbidity.
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