The COPERNICUS trial studied 2289 patients with severe heart failure with ejection fractions of 16–24% but free from overt fluid retention or recent treatment with intravenous diuretics. The results showed a highly significant 35% reduction in all-cause mortality caused by the drug, carvedilol.
The CAPRICORN study showed that in patients after myocardial infarction with an ejection fraction of 33% carvedilol caused a 23% relative reduction in mortality identical to that observed with ACE inhibitors. The MERIT-HF trial involved patients with class II and III heart failure with a mean ejection fraction of 28%, which resulted in risk reduction of 33% for total mortality or worsening heart failure. In this trial metoprolol was used in combination with diuretics, digoxin, and an ACE inhibitor.
In the CIBIS-II study of 2647 patients with class III heart failure and an ejection fraction of 35%, bisoprolol administration reduced all-cause mortality by
32% (p = 0.00005) and sudden death by 45% (p = 0.001). A 30% reduction in hospitalization occurred in the bisoprolol-treated group. Study patients received ACE inhibitors, diuretics, and digoxin.
COMET was a large randomized trial that compared carvedilol and metoprolol to clinical outcomes in patients with chronic heart failure. The COMET investigators assigned 1511 patients with chronic heart failure New York Heart Association class II–IV to treatment with carvedilol and 1518 to metoprolol. The all-cause mortality was 34% for carvedilol and 40% for metoprolol (p = 0.0017). Carvedilol showed superior beneficial effects compared to metoprolol and is the beta-blocker of choice for the management of heart failure.

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