Auerbach DS, et al. - The objective of this study is to examine whether anti-seizure medications (ASMs) alter the risk of cardiac events in patients with corrected QT (QTc) prolongation. Despite no change in overall QTc duration, pharmacogenomic investigations 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.

• In this study, they included people from the Rochester-based Long QT Syndrome (LQTS) Registry with baseline Qtc prolongation and history of ASM therapy (n=296).
• They evaluated the risk of recurrent cardiac events associated with ASM therapy by using multivariate Anderson-Gill models.
• They stratified by LQTS genotype and predominant mechanism of ASM action (Na+channel blocker & GABA modifier).
• An increased risk of cardiac events was seen when participants with QTcprolongation were taking vs. off ASMs (HR 1.65, 95%-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 related to an increased risk of cardiac events in participants with Qtc prolongation, particularly LQTS2, but reduced risk in LQTS1.
• The increased risk when taking all ASMs and Na+ channel blocker ASMs was attenuated by concurrent β-adrenergic blocker therapy (interaction, p<0.001).
• GABA modifier ASMs were related to an increased risk of events in patients not concurrently treated with β-adrenergic blockers.
• Female participants were at an increased risk of cardiac events while taking all ASMs and each class of ASMs.