Key result
Sodium channel blockers shortened QTc and reduced the incidence of cardiac events in patients with long QT syndrome.
Why the study?
Beta-blockers have genotype-dependent efficacy in LQTS, and while sodium channel blockers are recommended as add-on therapy for LQT3, their pooled effect across all LQTS patients remains unknown.
Do sodium channel blockers improve QTc and reduce cardiac events in patients with long QT syndrome?
Meta-Analysis (n=213)
Do sodium channel blockers improve QTc and reduce cardiac events in patients with long QT syndrome?
Answers are grounded in this paper and cite their sources.
Sodium channel blockers, particularly mexiletine, significantly shorten QTc and reduce cardiac events in patients with LQTS, with efficacy demonstrated in both LQT3 and LQT2.
BACKGROUND: β-Blockers are first-line therapy in patients with long QT syndrome (LQTS). However, β-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the pooled effect of sodium channel blockers in all LQTS patients remains unknown. METHODS: We conducted a systematic electronic search of PubMed, Embase, and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc ≥ 500 ms and QTc ≤ 460 ms in LQTS patients. RESULTS: Pooled analysis of 14 studies with 213 LQTS (9 LQT1 + 63 LQT2 + 135 LQT3 + 6 others) patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (mean difference [MD], -49.43; 95% confidence interval [CI], -57.80 to -41.05, p < .001), reduced the incidence of CEs (risk ratio [RR], 0.23; 95% CI, 0.11-0.47; p < .001) and the proportion of QTc ≥ 500 ms (RR, 0.33; 95% CI, 0.24-0.47; p < .001), and increased the proportion of QTc ≤ 460 ms (RR, 10.33; 95% CI, 4.62-23.09; p < .001). Sodium channel blockers significantly shortened QTc both in LQT3 and LQT2 patients, while the QTc shortening effect in LQT3 was superior to that in LQT2 (57.39 vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 vs. 49.08 vs. 50.10 ms). CONCLUSIONS: Sodium channel blockers can be useful both in LQT3 and LQT2 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.
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Yang et al. (2021) conducted a meta-analysis in Long QT syndrome (n=213). Sodium channel blockers was evaluated on QTc (MD -49.43, 95% CI -57.80 to -41.05, p=< .001). Sodium channel blockers shortened QTc and reduced the incidence of cardiac events in patients with long QT syndrome.
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