Evaluation of Cardiovascular Concerns of Intravenous Lacosamide Therapy in Epilepsy Patients

Abstract

ObjectiveVoltage-gated sodium channels (VGSCs) play an important role in neuronal excitability and epilepsies. In addition to the brain, VGSCs are also abundant enriched in cardiac tissues and are responsible for normal cardiac rhythm. Theoretically, sodium channel blocking antiseizure medications (SCB-ASMs) may have unwanted cardiac side effects. Lacosamide (LCM) is increasingly used in patients with status epilepticus (SE) due to the availability of intravenous formula. The concerns about the proarrhythmic effect are even higher due to the need for rapid administration of LCM. There were limited data on the cardiac safety of intravenous LCM. Hereby, we performed a study to observe the effect of intravenous loading of LCM in patients with seizures in our Neurological Intensive Care Unit (NICU).MethodsWe retrospectively reviewed the patients using parenteral LCM for seizures in NICU. A routine infusion time of 30 min was performed. The electrocardiogram (ECG) and blood pressure were recorded before and after LCM injection.ResultsWe retrospectively reviewed the clinical data of 38 patients using LCM for treating seizures. Two patients had cardiac side effects after LCM loading, one (3.0%) with new-onset first-degree AV block and the other (3.0%) with atrial premature complex. For the quantitative changes of ECG parameter analysis, there was no change in QRS complex, corrected QT intervals, and heart rate except that the PR interval was mildly increased. A mild decrease in the diastolic blood pressure and mean arterial pressure were also observed. None of the above-mentioned parameter alterations required clinical intervention.ConclusionWe evaluated the cardiac safety concern in real-world epilepsy patients requiring intravenous LCM. Near half of this cohort responded to LCM therapy and there was no life-threatening cardiac adverse effect. Intravenous LCM does have some effects on the ECG parameters and blood pressure but without clinical relevance. Despite the theoretical concern of cardiac adverse effects of LCM, the benefit of seizure control outweighed the risk in patients with status epilepticus or seizure clusters, such as hyperthermia, pulmonary edema, cardiac arrhythmias, or cardiovascular collapse.

Cardiac adverse events associated with lacosamide: a disproportionality analysis of the FAERS database

“…Kim et al reviewed medical records of consecutive adult epilepsy patients who received a single loading dose (400 mg) of IV LCM, 32.9% (28/85 patients) had experienced at least one cardiac AE 11 . Our mining data showed that cardiac adverse reactions had a higher proportion of serious outcomes (91% vs 74.29%) and a higher risk of life-threatening (14.48% vs 3.48%) than other adverse reactions, which is inconsistent with other studies 8 , 10 , 20 . Additionally, the median age of 49 years indicates that cardiac AEs can occur across a wide range of ages, emphasizing the need for vigilance regardless of the patient's age.…”

“…Experimental studies and clinical trials indicate that LCM affects neuronal and cardiac activity, potentially raising the likelihood of cardiac arrhythmias 19 . Like other anticonvulsant drugs, the dose-dependent inhibition of sodium channels by LCM may lead to delays in cardiac conduction below the level of the His bundle, potentially contributing to the development of cardiac arrhythmias 8 , 11 . The available studies on cardiac AEs associated with LCM use have limitations in sample size and lack of data stratification by sex, age, and weight, highlighting the importance of ongoing post-marketing surveillance.…”

“…In addition to the nervous system, VGSC are abundant in cardiac tissue and play a crucial role in maintaining normal rhythm. Theoretical considerations suggest that sodium channel blockade, as seen with some antiepileptic drugs, could lead to side effects on the heart, affecting its functioning 8 . For its cardiac adverse effects, sinus bradycardia, atrioventricular block, ventricular tachycardia, atrial fibrillation and atrial flutter have been reported successively after appearing on the market of LCM 8 , 9 .…”

“…Theoretical considerations suggest that sodium channel blockade, as seen with some antiepileptic drugs, could lead to side effects on the heart, affecting its functioning 8 . For its cardiac adverse effects, sinus bradycardia, atrioventricular block, ventricular tachycardia, atrial fibrillation and atrial flutter have been reported successively after appearing on the market of LCM 8 , 9 . Several large-scale studies have found that cardiac adverse events (AEs) associated with the oral administration of LCM, with an overall incidence ranging between 0.7% and 1.2% 9 , 10 .…”

Risk assessment of arrhythmias related to three antiseizure medications: a systematic review and single-arm meta-analysis

“…Both epilepsy and ASMs were found to be associated with an elevated risk of cardiovascular diseases. ASMs prolong the QT interval by closing ion channels or delaying their opening, thereby affecting cardiac rhythm and increasing the risk of arrhythmias in susceptible individuals, which provides a pathophysiological basis for ASM-induced arrhythmias ( 10–12 ).…”