Prof. B Kilickiran-Avci
Prof. Ali Oto,
Carvedilol and nebivolol are the third generation beta blockers of choice for heart failure together with the second generation beta blockers bisoprolol and metoprolol succinate.
Beta-adrenergic receptor blockers play an important role in the management of cardiovascular disease, including hypertension, ischemic heart disease and chronic heart failure. They differ, though, in beta-selectivity, vasodilation properties, and other ancillary features.
Recently, third generation, vasodilating, beta-blockers were introduced into practice.
Third generation beta blockers have distinctive vasodilator activity.
The vasodialtor effect of these three agents is obtained via the blockade of the alpha receptors. However nebivolol shows a highly selective beta-1 blocking effects and confers an endothelium dependent vasodilatation via activation of L-arginin/NO pathway.
After oral administration, absorption is fast and reaches maximum plasma concentration within 1-2 hours. The plasma half-life is 7-10 hours, and should be given twice daily. As it is metabolised mainly by the liver, the pharmacokinetics are changed in liver diseases.
Unlike traditional beta blockers carvedilol :
Its distinctive features allow different applications and usage and there are several trials for various conditions.
There is some evidence suggesting the preventive effects of carvedilol for nitrate tolerance (12). Side effects include rare vertigo, tiredness and headache. Erectile dysfunction may also be a problem.
Nebivolol is :
Blocks the alpha-1, beta-1 and beta-2 receptors and alpha-1 receptor blokade is responsible for the vasodilator effect. It has a partial agonist effect and is metabolised mainly by the liver.
Bucindolol is a non-selective and lipophilic beta blocker with a higher affinity then beta receptors. Vasodilator effects seem to be due to direct alpha-1 blockade(2).
BEST (Beta-Blocker Evaluation of Survival Trial) failed to show any benefit of bucindolol for total mortality in Class III-IV heart failure patients when added to the usual care (25). In the Class IV patients bucindolol even increased the composite end point of death and heart failure hospitalisations in six-months follow-up. The annual mortality for Class IV patients in the placebo group of the BEST study was 28 % which was higher than CIBIS (20 %), COPERNICUS (19 %) and MERIT-HF (25 %) studies. It has been suggested that the Class IV patients in BEST study were much sicker than the other studies and this contributed to the less beneficial effect of bucindolol in the BEST study.
Celiprolol is a third generation beta blocker with a weak beta-2 agonist activity and weak alpha 2 blocker and direct smooth muscle relaxing properties. It reduces peripheral vascular resistance and has similar antihypertensive effects to metoprolol, propronalol, atenolol and pindolol. In a study on heart failure patients comparing metoprolol, placebo and celiprolol, both drugs were well tolerated but celiprolol did not show any additional benefit (26,27).
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
All beta blockers are not the same in their effects. Although it seems that their antihypertensive efficacy is a class effect, it may not be easy to consider their beneficial effects in heart failure as a class effect. Moreover their metabolic effects are also different, third generation beta blockers being more neutral or positive.
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B.Kiliçkiran-Avci, MD**, A.Oto, MD, FESC, FACC, FHRS*, *Professor of Cardiology, Department of Cardiology, Hacettepe University. Faculty of Medicine **Lecturer in Cardiology, Department of Cardiology, Baskent University Faculty of Medicine Ankara-Turkey
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