☆ 4.5 Article

Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications

HEART (2015)

Journal

HEART

Volume 101, Issue 1, Pages 17-22

Publisher

BMJ PUBLISHING GROUP

DOI: 10.1136/heartjnl-2014-305664

Keywords

Funding

Netherlands Organization for Scientific Research (NWO) [ZonMW Vici 918.86.616, Mozaiek 017.003.084]
Dutch Medicines Evaluation Board (MEB/CBG)
European Community's Seventh Framework Programme (FP7, ARITMO) [241679]
Biobanking and Biomolecular Research Infrastructure The Netherlands (BBMRI-NL)
National Epilepsy Foundation Netherlands [10-07]
Physio Control
Netherlands Heart Foundation [2006B179]
Pfizer
Merck
Johnson Johnson
Altana
AstraZeneca
Boehringer
Eli Lilly
GlaxoSmithKline
Yamanouchi
Boehringer Ingelheim
Novartis

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Abstract

Objective Epilepsy is associated with increased risk for sudden cardiac death (SCD). We aimed to establish, in a community based study, whether this association is mediated by epilepsy per se, use of antiepileptic medications (AEMs), or both. Methods We studied SCD cases and age/sex matched controls in a case-control study in a large scale general practitioners' research database (n=478 661 patients). SCD risk for symptomatic epilepsy (seizure <2 years before SCD), stable epilepsy (no seizure <2 years before SCD), and use of AEMs (any indication) was determined. Results We identified 926 SCD cases and 9832 controls. Fourteen cases had epilepsy. Epilepsy was associated with an increased SCD risk (cases 1.5%, controls 0.5%; adjusted OR 2.8, 95% CI 1.4 to 5.3). SCD risk was increased for symptomatic epilepsy (cases 0.9%, controls 0.1%; adjusted OR 5.8, 95% CI 2.1 to 15.6), but not with stable epilepsy (cases 0.6%, controls 0.4%; adjusted OR 1.6, 95% CI 0.7 to 4.1). AEM use was found in 23 cases and was associated with an increased SCD risk (cases 2.5%, controls 0.8%; adjusted OR overall 2.6, 95% CI 1.5 to 4.3) among symptomatic epilepsy cases (cases 0.9%, controls 0.1%; adjusted OR 6.4, 95% CI 2.4 to 17.4) and non-epilepsy cases (cases 1.0%, controls 0.4%; adjusted OR 2.3, 95% CI 1.01 to 5.2). Increased SCD risk was associated with sodium channel blocking AEMs (cases 1.6%, controls 0.4%; adjusted OR 2.8, 95% CI 1.1 to 7.2), but not with non-sodium channel blocking AEMs. Carbamazepine and gabapentin were associated with increased SCD risk (carbamazepine: cases 1.1%, controls 0.3%; adjusted OR 3.2, 95% CI 1.1 to 9.2; gabapentin: cases 0.3%, controls 0.1%; adjusted OR 5.7, 95% CI 1.2 to 27.9). Conclusions Epilepsy and AEM use are both associated with increased SCD risk in the general population. Poor seizure control contributes to increased SCD risk in epilepsy, while sodium channel blockade contributes to SCD susceptibility in AEM users.

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Cardiac adverse effects of antiseizure medications

Gaetano Zaccara, Simona Lattanzi, Francesco Brigo

Summary: Patients with severe epilepsy are at increased risk of cardiovascular disease and arrhythmias, with some antiseizure medications having protective effects against cardiovascular events but also potentially cardiotoxic effects that need to be considered. Monitoring and consideration of cardiotoxic effects of ASMs are advisable in treatment selection.

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