Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Dose Related Patterns of Ventricular Arrhythmia due to Carvedilol Withdrawal in Patients with Systolic Heart Failure

Author(s): Kazuhiko Kido, Sara D. Brouse, Tracy E. Macaulay, Richard J. Charnigo and Paul Anaya

Volume 10, Issue 3, 2015

Page: [227 - 233] Pages: 7

DOI: 10.2174/1574886310666150427162904

Price: $65

Abstract

Objectives: This study evaluates the impact of carvedilol dose changes on the ventricular arrhythmia event rates for patients ≥ 18 years of age with systolic heart failure and examines dose dependent effects of carvedilol withdrawal in dose reduction and discontinuation subgroups.

Methods: This retrospective cohort study included patients with systolic heart failure (EF ≤ 40%) receiving carvedilol. The primary outcome was incidence of ventricular arrhythmia. Ventricular arrhythmia event rates were compared among carvedilol dose continuation, reduction and discontinuation groups. To assess dose dependent effects of beta-blocker withdrawal, dose reduction and discontinuation groups were divided into subgroups.

Results: Dose discontinuation (n=64) or reduction group (n=83) had significantly higher ventricular arrhythmia rates compared with dose continuation group (n=262) (65.6 vs 33.7 vs 15.3%, p < 0.001 for both comparisons). Dose discontinuation group also had a significantly higher ventricular arrhythmia event rate compared with dose reduction group (p<0.001). There were no significant differences in ventricular arrhythmia event rates among dose discontinuation or reduction subgroups.

Conclusion: Continuation of carvedilol therapy was associated with a substantially lower ventricular arrhythmia event rate compared with reduction or discontinuation of carvedilol therapy. Dose dependent effects of beta-blocker withdrawal in subgroup analyses were not found.

Keywords: Beta-blocker, beta-blocker withdrawal, carvedilol, heart failure, ventricular arrhythmia.

[1]
Yancy CW, Jessup M, Bozkurt B, et al. ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62: e147-239.
[2]
Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail 2010; 16: e1-e194.
[3]
McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the Europe Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012; 14: 803-69.
[4]
Frishman WH. Beta adrenergic blocker withdrawal. Am J Cardiol 1987; 59: 26F-32F.
[5]
Brouse SD, Hafezi S. Impact of beta-blocker dosage changes during heart failure exacerbation. J Pharm Technol 2006; 22: 79-85.
[6]
CIBIS Investigator and Committees. A randomized trial of betablockage in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation 1994; 90: 1765-73.
[7]
CIBIS-II authors. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomized trial. Lancet 1999; 353: 9-13.
[8]
MERIT-HF authors. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure. Lancet 1999; 353: 2001-7.
[9]
Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 1996; 334: 1349-55.
[10]
Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the mortality of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 2002; 106: 2194-9.
[11]
Cheng J, Niwa R, Kamiya K, Toyama J, Kodama I. Carvedilol blocks the repolarizing K+ currents and the L-type Ca2+ current in rabbit ventricular myocytes. Eur J Pharmacol 1999; 376: 189-201.
[12]
Karle CA, Kreye VA, Thomas D, et al. Antiarrhythmic drug carvedilol inhibits HERG potassium channels. Cardiovasc Res 2001; 49: 361-70.
[13]
Maltsev VA, Sabbab HN, Undrovinas AI. Down-regulation of sodium current in chronic heart failure: Effect of long-term therapy with carvedilol. Cell Mol Life Sci 2002; 59: 1561-8.
[14]
Butler J, Young JB, Abraham WT, et al. ESCAPE Investigators. Beta-blocker use and outcomes among hospitalized heart failure patients. J Am Coll Cardiol 2006; 47: 2462-9.
[15]
Metra M, Torp-Pedersen C, Cleland JG, et al. should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. Eur J of Heart Failure 2007; 9: 901-9.
[16]
Fonarow GC, Abraham WT, Albert NM, et al. OPTIMIZE-HF Investigators. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure. J Am Coll Cardiol 2008; 52: 190-9.
[17]
Jondeau G, Neuder Y, Eicher JC, et al. B-CONVINCED: beta-blocker continuation vs. interruption in patients with congestive heart failure hospitalized for a decompensated episode. Eur Heart J 2009; 30: 2186-92.
[18]
Parameswaran AC, Tang WH, Franis GS, Gupta R, Young JB. Why do patients fail to receive beta-blockers for chronic heart failure over time? A “real world” single-center, 2-year follow-up experience of beta-blocker therapy in patients with chronic heart failure. Am Heart J 2005; 149: 921-6.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy