Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Packer M， Fowler MB， Roecker EB， Coats AJ， Katus HA， Krum H， Mohacsi P， Rouleau JL， Tendera M， Staiger C， Holcslaw TL， Amann-Zalan I， DeMets DL; Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. College of Physicians and Surgeons， Columbia University， New York， NY 10032， USA. mp65@columbia.edu

BACKGROUND: Beta-blocking agents improve functional status and reduce morbidity in mild-to-moderate heart failure， but it is not known whether they produce such benefits in severe heart failure.

METHODS AND RESULTS: We randomly assigned 2289 patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction <25% (but not volume-overloaded) to double-blind treatment with either placebo (n=1133) or carvedilol (n=1156) for an average of 10.4 months. Carvedilol reduced the combined risk of death or hospitalization for a cardiovascular reason by 27% (P=0.00002) and the combined risk of death or hospitalization for heart failure by 31% (P=0.000004). Patients in the carvedilol group also spent 27% fewer days in the hospital for any reason (P=0.0005) and 40% fewer days in the hospital for heart failure (P<0.0001). These differences were as a result of both a decrease in the number of hospitalizations and a shorter duration of each admission. More patients felt improved and fewer patients felt worse in the carvedilol group than in the placebo group after 6 months of maintenance therapy (P=0.0009). Carvedilol-treated patients were also less likely than placebo-treated patients to experience a serious adverse event (P=0.002)， especially worsening heart failure， sudden death， cardiogenic shock， or ventricular tachycardia.

CONCLUSION: In euvolemic patients with symptoms at rest or on minimal exertion， the addition of carvedilol to conventional therapy ameliorates the severity of heart failure and reduces the risk of clinical deterioration， hospitalization， and other serious adverse clinical events.