Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study

A. C. Ruwald, G. H. Gislason, M. Vinther, J. B. Johansen, J. C. Nielsen, B. T. Philbert, C. Torp-Pedersen, S. Riahi, C. Jons

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94). Conclusion: In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

Original languageEnglish
JournalEuropace
Volume20
Issue numberFI2
Pages (from-to)F217-F224
ISSN1099-5129
DOIs
Publication statusPublished - 1. Sep 2018

Keywords

  • Carvedilol
  • Metoprolot
  • Implantable cardioverter-defibrillator
  • Metoprolot tartrate
  • Metoprolot succinate
  • Dose
  • Pharmacotherapy
  • Beta-blocker
  • Tachycardia, Ventricular/diagnosis
  • Humans
  • Middle Aged
  • Primary Prevention/instrumentation
  • Death, Sudden, Cardiac/epidemiology
  • Male
  • Dose-Response Relationship, Drug
  • Heart Failure/diagnosis
  • Time Factors
  • Defibrillators, Implantable
  • Female
  • Registries
  • Retrospective Studies
  • Adrenergic beta-Antagonists/administration & dosage
  • Carvedilol/administration & dosage
  • Metoprolol/administration & dosage
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • Hospitalization
  • Electric Countershock/adverse effects
  • Denmark/epidemiology
  • Ventricular Fibrillation/diagnosis
  • Aged

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