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Mexiletine therapy significantly reduce the number of life-threatening arrhythmic events in long QT syndrome type 3 patients (LQT3), according to research published in the Journal of the American College of Cardiology.
LQT3 is caused by gain-of-function mutations in the SCN5A gene, which codes for the alpha-subunit of the sodium channel NaV1.5. Mexelitine blocks late sodium current and shortens QT interval in LQT3 patients. However, the hypothesis that by shortening the QT interval, mexelitine can also reduce the occurrence of life-threatening arrhythmias has not yet been proven.
To determine the preventative effects on adverse events including arrhythmic syncope, aborted cardiac arrest, or sudden death, researchers compared the number of arrhythmic events per patient and the annual rateduring a 1-year observation period before and after the beginning of therapy with mexiletine.
A total of 34 LQT3 patients (median age: 22; 56% male) were included in the study. The median QTc (corrected QT) interval before therapy was 509 ms, and the median duration of oral mexiletine therapy was 36 months with an average daily dose of 8 ± 0.5 mg/kg.
“We reported here the first observation that a medication, other than beta-blockers, is able to reduce the occurrence of arrhythmic events in LQT3 patients, corroborating the hypothesis that mexiletine may improve survival in these patients,” the authors wrote.
“Overall our data supported the view that precision medicine can be applied to the management of LQTS patients, guiding not only risk stratification, but also the identification of therapies able to modify the molecular mechanism of the disease.”
Mexiletine significantly shortened QTc by 63 ± 6 ms (P<.0001) and reduced arrhythmic events from 22% to 3% (P=.031). The average number of arrhythmic events per patient was also reduced from 0.43 ± 0.17 to 0.03 ± 0.03 (P-.027) and the annual rate of arrhythmic events was reduced from 10.3% to 0.7% (P=.0097).
The authors noted that mexiletine therapy should be considered for patients with LQT3 who have QTc intervals >500 ms to reduce the risk of life-threatening arrhythmic events. “Clinical trials are needed to establish whether therapy with mexiletine should be adopted as a standard adjunct to the care of patients with LQT3,” they concluded.
Reference
Mazzanti A, Maragna R, Faragli A, et al. Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol. 2016; 67(9):1053-1058. doi: 10.1016/j.jacc.2015.12.033.
