Comparing beta-blocking effects of bisoprolol, carvedilol and nebivolol.
OBJECTIVE
Bisoprolol, carvedilol and nebivolol have been shown to be effective in the treatment of heart failure. However, the beta-blocking effects of these drugs have never been compared directly.


METHODS
Therefore, we performed a randomized, double-blind, placebo-controlled, cross-over trial in 16 healthy males. Subjects received 10 mg bisoprolol, 50 mg carvedilol, 10 mg nebivolol and placebo on the first morning followed by 5 mg bisoprolol once daily, 25 mg carvedilol twice daily, 5 mg nebivolol once daily and placebo for 1 week. Heart rate and blood pressure were measured at rest and exercise 3 and 24 h following intake of the first dose, and immediately before and 3 hours following intake of the last dose of each drug. In addition, effects of the drugs on nocturnal melatonin release were determined, and quality of life (QOL) was evaluated.


RESULTS
Heart rate at exercise was decreased at 3 h following intake of the first single dose of each drug by bisoprolol (-24%), carvedilol (-17%) and nebivolol (-15%), and at 24 h following intake of the respective last dose of each drug following 1 week of chronic administration by bisoprolol (-14%), carvedilol (12 h; -15%) and nebivolol (-13%) (p < 0.05 in all cases). Thus, trough-to-peak-ratios at long-term were as follows: Bisoprolol, 58%; carvedilol (12 h), 85%; nebivolol, 91%. Nocturnal melatonin release was decreased by bisoprolol (-44%, p < 0.05) whereas nebivolol and carvedilol had no effect. QOL with carvedilol was slightly but significantly lower than with the other drugs, whereas bisoprolol and nebivolol did not alter QOL.


CONCLUSIONS
These data show that peak beta-blocking effects of bisoprolol appear stronger than those of nebivolol and carvedilol. On the other hand, nebivolol exerts the highest trough-to-peak-ratio. However, beta-blocking effects of all the three drugs are similar at trough. Only bisoprolol but neither nebivolol nor carvedilol decreased nocturnal melatonin release, a feature which might cause sleep disturbances. Finally, only carvedilol slightly decreased QOL, whereas nebivolol and bisoprolol did not affect QOL. We conclude that different beta-blockers may exert clinically relevant different effects.
Stoschitzky
Kurt
K
Division of Cardiology, Department of Medicine, Medical University of Graz, Graz, Austria. kurt.stoschitzky@meduni-graz.at
Stoschitzky
Gergana
G
Brussee
Helmut
H
Bonelli
Claudia
C
Dobnig
Harald
H