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Our mission is to improve quality of life and longevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
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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.
(1) Feuerstein GZ, Ruffolo RR Jr. Carvedilol, a novel multiple action antihypertensive agent with antioxidant activity and the potential for myocardial and vascular protection. Eur Heart J 1995;16(suppl F): 38-42.
(2) Dunn CJ, Lea AP, Wagstaff AJ. Carvedilol: a reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs 1997;54:161-185.
(3) Agrawal B, Wolf K, Berger A, et al. Effect of antihypertensive treatment on qualitative estimates of microalbuminuria. J Hum Hypertens 1996;10:551-5. (4) Abraham WT, Tsvetkova T, Lowes BD, et al. Carvedilol improves renal hemodynamics in patients with chronic heart failure [abstract]. Circulation 1998;98:I-378–I-379. (5) Jacop S, Rett K, Wicklmayr M, et al. Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study. J Hypertens 1996;14:489-494.
(6) Poole-Wilson PA, Swedberg K, Cleland JG, et al, for the Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:7-13. (7) Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin- dependent diabetes mellitus and hypertension: a randomized controlled trial. Ann Intern Med 1997;126:955-959. (8) Colucci WS. Landmark Study: The Carvedilol Post-Infarct Survival Control in left ventricular dysfunction study (CAPRICORN). Am J Cardiol 2004;93(suppl):13B-16B. (9) Packer M, Bristow M, Cohn J, et al. The effect of carvedilol on mortality and morbidity in patients with chronic heart failure. N Engl J Med 1996;334:1349-1355. (10) Packer M, Coats AJS, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-1658. (11) MERIT-HF Investigators. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomized Intervention Trial in Congestive Heart failure (MERIT-HF). Lancet 1999;353:2001-2007. (12) El-Demerdash E. Evidences for prevention of nitroglycerin tolerance by carvedilol. Pharmacological Research 2006;53:380-385. (13) Troost R, Schwedhelm E, Rojczyk S et al. Nebivolol decreases systemic oxidative stress in healthy volunteers. British J Clin Pharmacol 2000;50:377-79. (14) Fratta Pasini AF, Garbin U, Nava MC, et al. Nebivolol decreases oxidative stress in essential hypertensive patients and increases nitric oxide by reducing its oxidative inactivation. J Hypertens 2005;23(3):589-96
(15) Brixius K, Bundkirchen, Bolck B et al. Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardium. Brit J Pharmacol 2001;133:1330-8. (16) Kakoki M, Hirata Y, Hayakawa H et al. Effects of vasodilatotory B-adrenoceptor antagonists on endothelium derived nitric oxide release in rat kidney. Hypertension 1999;33(part II):467-71. (17) Greven J, Gabriels G. Effect of nebivolol, a novel B1-selective adrenoceptor antagonist with vasodilating properties, on kidney function. Arzneim Forsch/drug Res 2000;50:973-79. (18) Fallois JV, Faulhaber H-D: Nebivolol, a beta-blocker of the third generation: the current treatment of arterial hypertension: results of a multicenter observational study. Praxis 2001;90:435-441.
(19) Weber MA. The Role of the new ?-blockers in treating cardiovascular disease. Am J Hypertens 2005;18;169S-176S.
(20) Falciani M, Rinaldii B, D’Agostino B, et al. Effects of nebivolol on human platelet aggregation. J Cardiovasc Pharmacol 2001;38:922-29.
(21) Brehm BR, Wolf SC, Bertsch D, et al. Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells. Cardiovasc Res 2001;49:430-9.
(22) Wisenbaugh T et al. Long-term (3 months) effect of new b-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. J Am Coll Cardiol 1993;21:1094-1100. (23) Nodari S, Meta M, Dei Cas L. Beta blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long-term effects of atenolol vs nebivolol. Eur J Heart Failure 2003;5:621-7. (24) Flather MD, Shibata MC, Coats AJS, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascusar hospital admission in elderly patients with heart failure (SENIORS). European Heart J 2005;26:215-225. (25) The Beta-Blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;344:1659-67. (26) Anderson JL, Krause-Steinrauf H, Goldman S, et al for the Beta-blocker Evaluation of Survival Trial (BEST) Investigators. Failure of benefit and early hazard of bucindolol for class IV heart failure. J of Cardiac Failure 2003;9:266-77. (27) Sanderson JE, Chan SKW, Yu CM. ß-blockers in heart failure: a comparison of a vasodilating ß-blocker with metoprolol. Heart 1998;79:86-92.
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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