Denmark: Study on Lamotrigine and Cardiac Risks

A new study reports that lamotrigine use is associated neither with the risk of cardiac conduction disorders in people without pre-existing cardiac morbidity nor with all-cause mortality in people with pre-existing cardiac morbidity. The article was published in Epilepsia.

Recently, the US FDA issued a warning against the use of Lamotrigine in people at risk of cardiac rhythm and conduction abnormalities. Lamotrigine is one of the most widely used antiseizure medications for epilepsy and bipolar disorders. The warning was issued after an in vitro study showed that lamotrigine may slightly inhibit cardiac sodium channels, giving rise to class IB antiarrhythmic activity. Also, there is concern that it may slow ventricular conduction and thus increase the risk of proarrhythmia and sudden death in people with structural or functional heart disease. Therefore, the lamotrigine label warns about its use in patients with cardiac conduction disorders (e.g., second or third-degree heart block), ventricular arrhythmias, and cardiac disease or abnormality. Concerns about the safety of treatment are central to the management of illness in people with epilepsy and bipolar disorder treated with lamotrigine. It is essential to address these concerns.

Christensen J, Aarhus University Hospital, Denmark, and colleagues initiated a study to assess the risk of cardiac morbidity and mortality in new users of lamotrigine.

Researchers followed 91,949 members aged ≥15 for the first 2 years after initiating lamotrigine therapy. Among the new users, 86,769 had no pre-existing cardiac disease and n = 5180 had pre-existing cardiac disease. The main outcomes were set as 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 were used for hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for comparison of the risk in current versus past users of lamotrigine.

Key Findings of the Study

• 23% of the users without pre-existing cardiac disease developed a cardiac conduction disorder.
• A comparison of the risk in current and past lamotrigine treatment periods yielded an adjusted HR of new-onset cardiac conduction disorder of 1.03.
• 22.2% of the users with pre-existing cardiac disease were reported dead.
• A comparison of the risk in current and past lamotrigine treatment periods yielded an adjusted HR for all-cause mortality of 1.05.

The authors conclude that the study recorded no increased risk of cardiac conduction disorders in persons without pre-existing cardiac morbidity, and no increased all-cause mortality in persons with pre-existing cardiac morbidity associated with lamotrigine use. Although observational studies cannot provide conclusive evidence, the risks associated with using lamotrigine were limited and the present study findings do not support the FDA warning against the use of lamotrigine.

Further studies evaluating the heart risk across the drug class of sodium channel blockers are highly relevant, as also suggested by the FDA, the authors wrote.

Reference

Christensen, J, Trabjerg, BB, Dreier, JW. Cardiac morbidity and mortality associated with the use of lamotrigine. Epilepsia. 2022; 00: 1–10. https://doi.org/10.1111/epi.17339