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

J Am Coll Cardiol. 2012 Nov 13;60(20):2092-9. doi: 10.1016/j.jacc.2012.07.046. Epub 2012 Oct 17.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Child
  • Disease-Free Survival
  • Electrocardiography / drug effects
  • Female
  • Humans
  • Long QT Syndrome / drug therapy*
  • Long QT Syndrome / mortality
  • Male
  • Metoprolol / pharmacology
  • Metoprolol / therapeutic use*
  • Nadolol / pharmacology
  • Nadolol / therapeutic use*
  • Prognosis
  • Propranolol / pharmacology
  • Propranolol / therapeutic use*
  • Secondary Prevention
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenergic beta-Antagonists
  • Nadolol
  • Propranolol
  • Metoprolol