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. 2022 Nov 22;24(11):1809-1823.
doi: 10.1093/europace/euac087.

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

Martijn H van der Ree  1 , Laura van Dussen  2   3 , Noa Rosenberg  2   3 , Nina Stolwijk  2   3 , Sibren van den Berg  2   3 , Vincent van der Wel  3 , Bart A W Jacobs  3   4 , Arthur A M Wilde  1 , Carla E M Hollak  2   3 , Pieter G Postema  1
Affiliations

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

Martijn H van der Ree et al. Europace. .

Abstract

Aims: While mexiletine has been used for over 40 years for prevention of (recurrent) ventricular arrhythmias and for myotonia, patient access has recently been critically endangered. Here we aim to demonstrate the effectiveness and safety of mexiletine in the treatment of patients with (recurrent) ventricular arrhythmias, emphasizing the absolute necessity of its accessibility.

Methods and results: Studies were included in this systematic review (PROSPERO, CRD42020213434) if the efficacy or safety of mexiletine in any dose was evaluated in patients at risk for (recurrent) ventricular arrhythmias with or without comparison with alternative treatments (e.g. placebo). A systematic search was performed in Ovid MEDLINE, Embase, and in the clinical trial registry databases ClinicalTrials.gov and ICTRP. Risk of bias were assessed and tailored to the different study designs. Large heterogeneity in study designs and outcome measures prompted a narrative synthesis approach. In total, 221 studies were included reporting on 8970 patients treated with mexiletine. Age ranged from 0 to 88 years. A decrease in ventricular arrhythmias of >50% was observed in 72% of the studies for pre-mature ventricular complexes, 64% for ventricular tachycardia, and 33% for ventricular fibrillation. Electrocardiographic effects of mexiletine were small; only in a subset of patients with primary arrhythmia syndromes, a relative (desired) QTc decrease was reproducibly observed. As for adverse events, gastrointestinal complaints were most frequently observed (33% of the patients).

Conclusions: In this systematic review, we present all the currently available knowledge of mexiletine in patients at risk for (recurrent) ventricular arrhythmias and show that mexiletine is both effective and safe.

Keywords: Mexiletine; Systematic review; Ventricular arrhythmias.

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Conflict of interest statement

Conflict of interest: P.G.P. is a member of the Scientific Advisory Group on Cardiovascular Issues (SAG-CVS) of the EMA since 2021. C.E.M.H. is involved in pre-marketing research with Sanofi, Protalix, and Idorsia, outside the submitted work. N.R., N.S., S.B., V.W., B.J., and C.E.M.H. are members of the platform ‘Medicijn voor de Maatschappij’. This is an academic initiative that aims to support sustainable access to medicines for rare diseases, including mexiletine. V.W. reports personal fees from Fair Medicine Foundation, personal fees from Patient One, outside the submitted work.

Figures

Figure 1
Figure 1
Flow chart of study inclusion.
See this image and copyright information in PMC

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