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

Background: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta 1-, beta 2- and alpha 1-blocker, vs. metoprolol tartrate, a beta 1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit front 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. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.