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

摘要

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.