Role of Beta-blockers in Treatment of Heart Failure

Duk-Kyung Kim; Sue Jin Kim

doi:10.5124/jkma.2007.50.3.274

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Kim and Kim: Role of Beta-blockers in Treatment of Heart Failure

Continuing Education Column

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2007; 50(3): 274-278.

Published online: 31 March 2007

DOI: https://doi.org/10.5124/jkma.2007.50.3.274

Role of Beta-blockers in Treatment of Heart Failure

Duk-Kyung Kim, MD, Sue Jin Kim, MD

Department of Internal Medicine, Sungkyunkwan University School of Medicine, Korea. dkkim@smc.samsung.co.kr, koroh78@empal.com

Abstract

Anti-adrenergic medication is very important to the treatment of chronic heart failure because a failing human heart is adrenergically activated. The increase in cardiac adrenergic drive and circulating norepinephrine are damaging to a failing heart. Certain beta-blockers have been shown to improve the cardiac function and symptoms and to reduce the risk of death and hospitalization in patients with heart failure. Recently, the third-generation beta-blockers have emerged for the treatment of heart failure. This article reviews the neurohormonal pathophysiology of heart failure and the different beta-blockers and their effects.

Keywords: Heart failure, Beta-blocker

Figures and Tables

Figure 1

Impact on mortality of carvedilol use at discharge compared with no β blocker at discharge in eligible patients without contraindications

Log-rank test: P<.004

Table 1

Summary of selected clinical trials evaluating beta-blockade therapy in CHF

Differences are statistically significant unless otherwise indicated

Abbreviations: Ex HR, exercise heart rate; LVEF, left ventricular ejection fraction; NA, not applicable; NS, not statistically significant; SD, sudden death

^*Approximate equivalence of metoprolol titrate

^†Decrease in mean heart rate (not exercise heart rate)

^‡Difference compared with metoprolol

MDC=Metoprolol in dilated cardiomyopathy

CIBIS=Cardiac insufficiency bisoprolol study

COPERNICUS=The carvedilol prospective randomized cumulative survival trial

MERIT-HF=The metoprolol CR / XL randomised intervention trial in congestive heart failure

COMET=Commentary on the carvedilol or metoprolol European trial

BEST=Beta-blocker evaluation of survival trial

Table 2

Clinical outcomes of follow-up cohort with LVSD by carvedilol use at discharge

IR=Interquartile range

LVSD=Left ventricular systolic dysfunction

SD=Standard deviation

Table 3

Adrenergic receptor blocking affinities of beta-blocking agent in human receptors^*

^*Beta receptors are the average of data from radiological binding data in myocardial membranes and recombinant receptors, and inhibition in functional assays; alpha1 receptors are from myocardial membranes. Metoprolol and bisoprolol data are from radiological binding data in myocardial membranes. Nebivolol data are from another laboratory, in guinea pig receptor preparations

^†K(Beta1) = average of high-affinity dissociation constant determined from ¹²⁵I-CYP competition curves in human ventricular myocardial membranes, dissociation constant determined from competition curves in transfected cells expressing recombinant human beta1 receptors, and dissociation constant determined from inhibition of isoproterenol-mediated stimulation of muscle contraction in preparations of nonfailing human heart.

K(Beta2) = average of low-affinity dissociation constant determined from ¹²⁵I-CYP competition curves, dissociation constant determined from simple curve fitting in transfected cells expressing recombinant human beta2 receptors, and dissociation constant determined from inhibition of isoproterenol-mediated stimulation of adenyl cyclase in membrane preparations of human heart.

K(Alpha₁) = dissociation constant determined from ¹²⁵I-BE2254 competition curves in human ventricular myocardial membranes

^‡Based on an alpha1 K1 of 69 nM in human saphenous vein ring segments

References

1. Eichhorn EJ, Bristow MR. Practical guidelines for initiation of beta-adrenergic blockade in patients with chronic heart failure. Am J Cardiol. 1997. 79:794–798.

2. Haber HL, Simek CL, Gimple LW, Bergin JD, Subbiah K, Jayaweera AR, Powers ER, Feldman MD. Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy? Circulation. 1993. 88:1610–1619.

3. Kaye DM, Lefkovits J, Jennings GL, Bergin P, Broughton A, Esler MD. Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol. 1995. 26:1257–1263.

4. Brodde OE, Schuler S, Kretsch R, Brinkmann M, Borst HG, Hetzer R, Reidemeister JC, Warnecke H, Zerkowski HR. Regional distribution of beta-adrenoceptors in the human heart: coexistence of functional beta 1-and beta 2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy. J Cardiovasc Pharmacol. 1986. 8:1235–1242.

5. Bristow MR. Changes in myocardial and vascular receptors in heart failure. J Am Coll Cardiol. 1993. 22:A61–A71.

6. Mann DL, Kent RL, Parsons B, Cooper GT. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation. 1992. 85:790–804.

7. Packer M. Beta-adrenergic blockade in chronic heart failure: principles, progress, and practice. Prog Cardiovasc Dis. 1998. 41:39–52.

8. Lowes BD, Gilbert EM, Abraham WT, Minobe WA, Larrabee P, Ferguson D, Wolfel EE, Lindenfeld J, Tsvetkova T, Kobertson AD, Ouaife RA, Bristow MR. Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. N Engl J Med. 2002. 346:1357–1365.

9. Reiter MJ. Cardiovascular drug class specificity: beta-blockers. Prog Cardiovasc Dis. 2004. 47:11–33.

10. Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, O'Connor CM, Sun JL, Yancy C, Young JB. Carvedilol use at discharge in patients hospitalized for heart failure is associated with improved survival: an analysis from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). Am Heart J. 2007. 153:82. e1–82. e11.

11. Bristow MR. beta-adrenergic receptor blockade in chronic heart failure. Circulation. 2000. 101:558–569.

12. Newton GE, Azevedo ER, Parker JD. Inotropic and sympathetic responses to the intracoronary infusion of a beta2-receptor agonist: a human in vivo study. Circulation. 1999. 99:2402–2407.

13. Bristow MR. Mechanism of action of beta-blocking agents in heart failure. Am J Cardiol. 1997. 80:L26–L40.

14. Le Coz F, Sauleman P, Poirier JM, Cuche JL, Midavaine M, Rames A, Le cocq B, Jaillon P. Oral pharmacokinetics of bisoprolol in resting and exercising healthy volunteers. J Cardiovasc Pharmacol. 1991. 18:28–34.

15. Nichols AJ, Gellai M, Ruffolo RR Jr. Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991. 5:25–38.

16. Gilbert EM, Abraham WT, Olsen S, Hattler B, White M, Mealy P, Larrabee P, Bristow MR. Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation. 1996. 94:2817–2825.

17. Yoshikawa T, Port JD, Asano K, Chidiak P, Bouvier M, Dutcher D, Roden RL, Minobe W, Tremmel KD, Bristow MR. Cardiac adrenergic receptor effects of carvedilol. Eur Heart J. 1996. 17:S. 8–16.

18. Gilbert EM, Anderson JL, Deitchman D, Yanowitz FG, O'Connell JB, Renlund DG, Bartholomew M, Mealey PC, Larrabee P, Bristow MR. Long-term beta-blocker vasodilator therapy improves cardiac function in idiopathic dilated cardiomyopathy: a double-blind, randomized study of bucindolol versus placebo. Am J Med. 1990. 88:223–229.

19. Cockcroft JR, Chowienczyk PJ, Brett SE, Chen CP, Dupont AG, Van Nueten L, Wooding SJ, Ritter JM. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther. 1995. 274:1067–1071.

20. Uhlir O, Dvorak I, Gregor P, Malek I, Spinarova L, Vojacek J, Van Nueten L. Nebivolol in the treatment of cardiac failure: a double-blind controlled clinical trial. J Card Fail. 1997. 3:271–276.

21. Lechat P, Escolano S, Golmard JL, Lardoux H, Witchitz S, Henneman JA, Maisch B, Hetzel M, Jaillon P, Boissel JP, Mallet A. Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency BIsoprolol Study (CIBIS). Circulation. 1997. 96:2197–2205.

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