Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol

Abstract

Objectives: The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS).

Background: Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective.

Methods: Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented.

Results: Patients (56% female, 27% symptomatic, heart rate 76 ± 16 beats/min, QTc 472 ± 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol.

Conclusions: Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.

Figure 1

Effect of baseline QTc on QTc-shortening. Baseline QTc was taken as normal if ≤450 ms, borderline if 451–480 ms and prolonged if >480 ms. Δ indicates change in ECG parameter with beta-blocker initiation.

Figure 2

Progression of QTc (mean ± SD) with initiation of propranolol and subsequent switch to metoprolol in a subset of 14 patients. ‘Baseline’ indicates QTc immediately prior to initiation of propranolol therapy; ‘Propranolol’ indicates first QTc measurement on propranolol; ‘Prior to switch’, QTc on propranolol prior to switch; ‘At switch’, QTc on propranolol at the time the decision to switch was made; ‘Metoprolol’, QTc on metoprolol after switch; TI, time interval in months.

Figure 3

Occurrence of BCEs in patients with symptoms prior to therapy. BCEs occurred in 8% of patients on propranolol, 7% of patients on nadolol, and 29% of patients on metoprolol.

Figure 4

Kaplan-Meier estimates of event-free survival of symptomatic patients initiated on different beta-blockers. The cumulative event-free survival of symptomatic patients initiated on metoprolol (n=35) was significantly different (p=0.02) from those initiated on propranolol and nadolol combined (n=66).