Exchange of beta-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial)

Eur J Heart Fail. 2005 Jun;7(4):640-9. doi: 10.1016/j.ejheart.2004.09.010.

Abstract

Background: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta1-, beta2- and alpha1-blocker, vs. metoprolol tartrate, a beta1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol.

Aim: To investigate the safety and tolerability of switching beta-blockers in CHF.

Methods: At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label beta-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days.

Results: 1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second beta-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from beta-blockade.

Conclusion: Our data show that switching beta-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Blood Pressure / drug effects
  • Carbazoles / administration & dosage
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Female
  • Heart Failure / drug therapy*
  • Heart Rate / drug effects
  • Humans
  • Male
  • Metoprolol / administration & dosage
  • Metoprolol / pharmacology
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Propanolamines / administration & dosage
  • Propanolamines / pharmacology
  • Propanolamines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Metoprolol