Failure of benefit and early hazard of bucindolol for Class IV heart failure

Jeffrey L. Anderson, Heidi Krause-Steinrauf, Steven Goldman, Barry S. Clemson, Michael J. Domanski, W. David Hager, David R. Murray, Douglas L. Mann, Barry M. Massie, Dennis M. McNamara, Ron Oren, William J. Rogers

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objectives: The risks and benefits of β-blockade with bucindolol were assessed in heart failure (HF) patients with Class IV symptoms within the Beta-blocker Evaluation of Survival Trial (BEST). Background: β-blockade is accepted therapy for mild to moderate HF, but its safety and efficacy in advanced HF have not been established. Methods: BEST recruited 2708 HF patients; of these, 226 with Class IV symptoms (n = 114 randomized to bucindolol, n = 112 to placebo) formed the basis of this study. All-cause death, HF hospitalization, and drug discontinuations occurring early during therapy (≤56 months) and overall during follow-up were assessed. Compared with Class III, Class IV patients were older and had higher plasma norepinephrine levels, prevalence of coronary disease, S3 gallops, and lower ejection fractions, but characteristics of the 2 Class IV treatment groups were similar. Results: During a mean of 1.6 years, 49% Class IV patients died, and 54% were hospitalized for HF. Bucindolol increased the combined endpoint of death or HF hospitalization within the first 6 months (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1-2.7) and did not result in benefit overall (HR = 1.2, 95% CI = 0.9-1.6). HF hospitalization alone within 6 months was increased by bucindolol (HR = 1.7), and an early adverse trend for death was seen (HR = 1.6) with no benefit overall (HR = 1.1). Bucindolol was discontinued more frequently than placebo for worsening HF (11% versus 4%) and hypotension (3% versus 0%). Conclusions: Class IV HF patients in BEST were at high risk. Bucindolol did not reduce death or HF hospitalization and was associated with early hazard.

Original languageEnglish (US)
Pages (from-to)266-277
Number of pages12
JournalJournal of Cardiac Failure
Volume9
Issue number4
DOIs
StatePublished - Aug 2003
Externally publishedYes

Fingerprint

Heart Failure
Hospitalization
Survival
bucindolol
Placebos
Confidence Intervals
Secondary Prevention
Hypotension
Coronary Disease
Cause of Death
Norepinephrine
Safety
Therapeutics
Pharmaceutical Preparations

Keywords

  • β-blocker
  • Bucindolol
  • Heart failure
  • Survival

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Anderson, J. L., Krause-Steinrauf, H., Goldman, S., Clemson, B. S., Domanski, M. J., Hager, W. D., ... Rogers, W. J. (2003). Failure of benefit and early hazard of bucindolol for Class IV heart failure. Journal of Cardiac Failure, 9(4), 266-277. https://doi.org/10.1054/jcaf.2003.42

Failure of benefit and early hazard of bucindolol for Class IV heart failure. / Anderson, Jeffrey L.; Krause-Steinrauf, Heidi; Goldman, Steven; Clemson, Barry S.; Domanski, Michael J.; Hager, W. David; Murray, David R.; Mann, Douglas L.; Massie, Barry M.; McNamara, Dennis M.; Oren, Ron; Rogers, William J.

In: Journal of Cardiac Failure, Vol. 9, No. 4, 08.2003, p. 266-277.

Research output: Contribution to journalArticle

Anderson, JL, Krause-Steinrauf, H, Goldman, S, Clemson, BS, Domanski, MJ, Hager, WD, Murray, DR, Mann, DL, Massie, BM, McNamara, DM, Oren, R & Rogers, WJ 2003, 'Failure of benefit and early hazard of bucindolol for Class IV heart failure', Journal of Cardiac Failure, vol. 9, no. 4, pp. 266-277. https://doi.org/10.1054/jcaf.2003.42
Anderson JL, Krause-Steinrauf H, Goldman S, Clemson BS, Domanski MJ, Hager WD et al. Failure of benefit and early hazard of bucindolol for Class IV heart failure. Journal of Cardiac Failure. 2003 Aug;9(4):266-277. https://doi.org/10.1054/jcaf.2003.42
Anderson, Jeffrey L. ; Krause-Steinrauf, Heidi ; Goldman, Steven ; Clemson, Barry S. ; Domanski, Michael J. ; Hager, W. David ; Murray, David R. ; Mann, Douglas L. ; Massie, Barry M. ; McNamara, Dennis M. ; Oren, Ron ; Rogers, William J. / Failure of benefit and early hazard of bucindolol for Class IV heart failure. In: Journal of Cardiac Failure. 2003 ; Vol. 9, No. 4. pp. 266-277.
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abstract = "Objectives: The risks and benefits of β-blockade with bucindolol were assessed in heart failure (HF) patients with Class IV symptoms within the Beta-blocker Evaluation of Survival Trial (BEST). Background: β-blockade is accepted therapy for mild to moderate HF, but its safety and efficacy in advanced HF have not been established. Methods: BEST recruited 2708 HF patients; of these, 226 with Class IV symptoms (n = 114 randomized to bucindolol, n = 112 to placebo) formed the basis of this study. All-cause death, HF hospitalization, and drug discontinuations occurring early during therapy (≤56 months) and overall during follow-up were assessed. Compared with Class III, Class IV patients were older and had higher plasma norepinephrine levels, prevalence of coronary disease, S3 gallops, and lower ejection fractions, but characteristics of the 2 Class IV treatment groups were similar. Results: During a mean of 1.6 years, 49{\%} Class IV patients died, and 54{\%} were hospitalized for HF. Bucindolol increased the combined endpoint of death or HF hospitalization within the first 6 months (hazard ratio [HR] = 1.7, 95{\%} confidence interval [CI] = 1.1-2.7) and did not result in benefit overall (HR = 1.2, 95{\%} CI = 0.9-1.6). HF hospitalization alone within 6 months was increased by bucindolol (HR = 1.7), and an early adverse trend for death was seen (HR = 1.6) with no benefit overall (HR = 1.1). Bucindolol was discontinued more frequently than placebo for worsening HF (11{\%} versus 4{\%}) and hypotension (3{\%} versus 0{\%}). Conclusions: Class IV HF patients in BEST were at high risk. Bucindolol did not reduce death or HF hospitalization and was associated with early hazard.",
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AU - Domanski, Michael J.

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AU - Murray, David R.

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