Many antiseizure medications (ASMs) affect ion channel function. We investigated whether
ASMs alter the risk of cardiac events in patients with corrected QT (QTc) prolongation. The study included people from the Rochester-based Long QT syndrome
(LQTS) Registry with baseline QTc prolongation and history of ASM therapy (n = 296). Using multivariate Anderson-Gill
models, we assessed the risk of recurrent cardiac events associated with ASM therapy.
We stratified by LQTS genotype and predominant mechanism of ASM action (Na+ channel blocker and gamma-aminobutyric acid modifier.) There was an increased risk
of cardiac events when participants with QTc prolongation were taking vs off ASMs (HR 1.65, 95% confidence interval [CI] 1.36–2.00,
P < 0.001). There was an increased risk of cardiac events when LQTS2 (HR 1.49, 95%
CI 1.03–2.15, P = 0.036) but not LQTS1 participants were taking ASMs (interaction, P = 0.016). Na+ channel blocker ASMs were associated with an increased risk of cardiac events in
participants with QTc prolongation, specifically LQTS2, but decreased risk in LQTS1. The increased risk
when taking all ASMs and Na+ channel blocker ASMs was attenuated by concurrent beta-adrenergic blocker therapy
(interaction, P < 0.001). Gamma-aminobutyric acid modifier ASMs were associated with an increased
risk of events in patients not concurrently treated with beta-adrenergic blockers.
Female participants were at an increased risk of cardiac events while taking all ASMs
and each class of ASMs. Despite no change in overall QTc duration, pharmacogenomic analyses set the stage for future prospective clinical
and mechanistic studies to validate that ASMs with predominantly Na+ channel blocking actions are deleterious in LQTS2, but protective in LQTS1.
Abbreviations:
ASM (antiseizure medication), GABA (gamma-aminobutyric acid), ECG (electrocardiogram), LQTS (Long QT syndrome), Na+Ch (Na+ channel), QTc (corrected QT), SCD (sudden cardiac death), SUDEP (sudden unexpected death in epilepsy)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: October 20, 2017
Accepted:
October 7,
2017
Received in revised form:
October 2,
2017
Received:
June 16,
2017
Footnotes
David S. Auerbach, PhD, is a Research Assistant Professor in the Department of Medicine and Department of Pharmacology/Physiology at the University of Rochester School of Medicine. Dr. Auerbach takes a multisystem “bench-to-bedside” approach to studying ion channel diseases of the brain and heart. The long-term goal of his research program is to understand the mechanisms for electrical disturbances in both the brains and hearts of patients with genetic ion channel diseases. Ultimately, his team aims to develop novel biomarkers to predict which patients are at a high risk of seizures, arrhythmias, and sudden death. His article is based on a presentation given at the annual meeting of the Central Society for Clinical and Translational Research in April 2017.
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