Abstract
OBJECTIVE: This study aims to compare the efficacy of different types of beta-blockers in preventing arrhythmias in patients with long QT syndrome (LQTS), and simultaneously analyze the relationship between dose and effect within each drug by incorporating dose as a continuous covariate. METHODS: A systematic search was conducted in the electronic database, with the cutoff date set at July 20, 2025. The search scope was limited to observational studies that compared at least two drug strategies. A Bayesian arm random-effects network meta-analysis (NMA) was performed, in which the daily equivalent dose (mg/day) was included as a continuous covariate to explore the dose-response relationship. RESULTS: This analysis included 5,692 patients with LQTS from 10 cohort studies. In LQT1, nadolol was superior to propranolol (RR = 0.59, 95% CI: 0.39-0.90) and had the highest probability of being the optimal treatment (SUCRA = 0.92). Dose-response trends for all drugs were non-significant (all p > 0.05). For LQT2, no beta-blocker showed significant superiority, though nadolol (SUCRA = 0.78) and propranolol (SUCRA = 0.65) were ranked highest; nadolol alone demonstrated a significant dose-effect relationship (slope = -0.01763, p = 0.010). In LQT3, no active treatment differed significantly from atenolol, yet SUCRA values favored nadolol (0.85) and propranolol (0.75). A significant dose-response was observed for nadolol (slope = -0.02136, p = 0.023). An unexpected risk reduction was noted for placebo versus atenolol (RR = 0.63, 95% CI: 0.42-0.93, p = 0.02), likely due to baseline imbalances. Evidence consistency (node split p > 0.38) and sensitivity analyses supported the robustness of these findings. CONCLUSION: Nadolol demonstrates significant and consistent clinical advantages in LQT1 patients and should be considered as first-line therapy for this subtype. In LQT2 patients, nadolol not only shows a superiority trend but also has a significant dose-effect relationship, supporting its clinical priority; in LQT3 patients, nadolol exhibits a significant dose-dependent risk reduction trend, though no statistically significant differences in efficacy were observed among all beta-blockers. Additionally, LQT3 patients should be cautious of the potential risks associated with atenolol.