Safety and efficacy of carvedilol in severe heart failure

Jay N. Cohn, Michael B. Fowler, Michael R. Bristow, Wilson S. Colucci, Edward M. Gilbert, Vithal Kinhal, Steven K. Krueger, Thierry Lejemtel, Kenneth A. Narahara, Milton Packer, Sarah T. Young, Terry L. Holcslaw, Mary Ann Lukas

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Background: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. Methods and Results: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). Conclusion: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
JournalJournal of Cardiac Failure
Volume3
Issue number3
StatePublished - 1997

Fingerprint

Heart Failure
Safety
Placebos
Clinical Trials Data Monitoring Committees
Quality of Life
carvedilol
Digoxin
Left Ventricular Function
Angiotensin-Converting Enzyme Inhibitors
Diuretics
Pharmaceutical Preparations
Stroke Volume
Multicenter Studies
Hospitalization
Therapeutics
Exercise
Physicians
Mortality
Population

Keywords

  • Beta-blocker
  • Carvedilol
  • Heart failure
  • Quality of life

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cohn, J. N., Fowler, M. B., Bristow, M. R., Colucci, W. S., Gilbert, E. M., Kinhal, V., ... Lukas, M. A. (1997). Safety and efficacy of carvedilol in severe heart failure. Journal of Cardiac Failure, 3(3), 173-179.

Safety and efficacy of carvedilol in severe heart failure. / Cohn, Jay N.; Fowler, Michael B.; Bristow, Michael R.; Colucci, Wilson S.; Gilbert, Edward M.; Kinhal, Vithal; Krueger, Steven K.; Lejemtel, Thierry; Narahara, Kenneth A.; Packer, Milton; Young, Sarah T.; Holcslaw, Terry L.; Lukas, Mary Ann.

In: Journal of Cardiac Failure, Vol. 3, No. 3, 1997, p. 173-179.

Research output: Contribution to journalArticle

Cohn, JN, Fowler, MB, Bristow, MR, Colucci, WS, Gilbert, EM, Kinhal, V, Krueger, SK, Lejemtel, T, Narahara, KA, Packer, M, Young, ST, Holcslaw, TL & Lukas, MA 1997, 'Safety and efficacy of carvedilol in severe heart failure', Journal of Cardiac Failure, vol. 3, no. 3, pp. 173-179.
Cohn JN, Fowler MB, Bristow MR, Colucci WS, Gilbert EM, Kinhal V et al. Safety and efficacy of carvedilol in severe heart failure. Journal of Cardiac Failure. 1997;3(3):173-179.
Cohn, Jay N. ; Fowler, Michael B. ; Bristow, Michael R. ; Colucci, Wilson S. ; Gilbert, Edward M. ; Kinhal, Vithal ; Krueger, Steven K. ; Lejemtel, Thierry ; Narahara, Kenneth A. ; Packer, Milton ; Young, Sarah T. ; Holcslaw, Terry L. ; Lukas, Mary Ann. / Safety and efficacy of carvedilol in severe heart failure. In: Journal of Cardiac Failure. 1997 ; Vol. 3, No. 3. pp. 173-179.
@article{c66128e35f4f4dbfb11d988667d0d51a,
title = "Safety and efficacy of carvedilol in severe heart failure",
abstract = "Background: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. Methods and Results: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8{\%}) did not complete the open-label period because of adverse events and 11.4{\%} in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). Conclusion: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.",
keywords = "Beta-blocker, Carvedilol, Heart failure, Quality of life",
author = "Cohn, {Jay N.} and Fowler, {Michael B.} and Bristow, {Michael R.} and Colucci, {Wilson S.} and Gilbert, {Edward M.} and Vithal Kinhal and Krueger, {Steven K.} and Thierry Lejemtel and Narahara, {Kenneth A.} and Milton Packer and Young, {Sarah T.} and Holcslaw, {Terry L.} and Lukas, {Mary Ann}",
year = "1997",
language = "English (US)",
volume = "3",
pages = "173--179",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "3",

}

TY - JOUR

T1 - Safety and efficacy of carvedilol in severe heart failure

AU - Cohn, Jay N.

AU - Fowler, Michael B.

AU - Bristow, Michael R.

AU - Colucci, Wilson S.

AU - Gilbert, Edward M.

AU - Kinhal, Vithal

AU - Krueger, Steven K.

AU - Lejemtel, Thierry

AU - Narahara, Kenneth A.

AU - Packer, Milton

AU - Young, Sarah T.

AU - Holcslaw, Terry L.

AU - Lukas, Mary Ann

PY - 1997

Y1 - 1997

N2 - Background: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. Methods and Results: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). Conclusion: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

AB - Background: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. Methods and Results: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). Conclusion: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

KW - Beta-blocker

KW - Carvedilol

KW - Heart failure

KW - Quality of life

UR - http://www.scopus.com/inward/record.url?scp=0031230455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031230455&partnerID=8YFLogxK

M3 - Article

C2 - 9330125

AN - SCOPUS:0031230455

VL - 3

SP - 173

EP - 179

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 3

ER -