Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: Results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) Trial

Mona Fiuzat, Daniel Wojdyla, Dalane Kitzman, Jerome Fleg, Steven J. Keteyian, William E. Kraus, Ileana L. Pina, David Whellan, Christopher M. O'Connor

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Objectives: This study sought to examine the association between baseline beta-blocker (BB) dose and outcomes in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial. Background: Beta-blockers reduce morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction, but it is unclear whether titrating to higher BB doses improves outcomes in this setting. Methods: The HF-ACTION trial was a randomized, multicenter trial enrolling 2,331 ambulatory HF patients with systolic dysfunction (New York Heart Association functional class II to IV, left ventricular ejection fraction <0.35) randomized to exercise training versus usual care, with median follow-up of 2.5 years. The BB dose at baseline was standardized with carvedilol equivalents and analyzed as a continuous variable and by discrete dose groups. The relationship between BB dose and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints was determined before and after adjustment for variables significantly associated with outcomes in the HF-ACTION cohort. Results: Ninety-five percent of patients were receiving a BB. There was a significant inverse relationship between BB dose and all-cause death or hospitalization but not other cardiovascular endpoints after adjustment for other predictors of outcome, with a linear benefit up to the 50-mg daily dose. There was a significant association between BB dose and change in peak VO 2 at 3 months. There was no increase in bradycardia with higher doses of BB. Conclusions: There was a significant inverse relationship between BB dose and the endpoint of all-cause death or all-cause hospitalization in this well-treated HF cohort with systolic dysfunction, supporting recommendations that titrating doses up to 50 mg/day might confer a benefit in such patients.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalJournal of the American College of Cardiology
Volume60
Issue number3
DOIs
StatePublished - Jul 17 2012

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Heart Failure
Exercise
Hospitalization
Cause of Death
Mortality
Bradycardia
Stroke Volume
Multicenter Studies
Morbidity

Keywords

  • beta-blockers
  • dose
  • exercise
  • heart failure
  • mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction : Results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) Trial. / Fiuzat, Mona; Wojdyla, Daniel; Kitzman, Dalane; Fleg, Jerome; Keteyian, Steven J.; Kraus, William E.; Pina, Ileana L.; Whellan, David; O'Connor, Christopher M.

In: Journal of the American College of Cardiology, Vol. 60, No. 3, 17.07.2012, p. 208-215.

Research output: Contribution to journalArticle

Fiuzat, Mona ; Wojdyla, Daniel ; Kitzman, Dalane ; Fleg, Jerome ; Keteyian, Steven J. ; Kraus, William E. ; Pina, Ileana L. ; Whellan, David ; O'Connor, Christopher M. / Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction : Results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) Trial. In: Journal of the American College of Cardiology. 2012 ; Vol. 60, No. 3. pp. 208-215.
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AU - Wojdyla, Daniel

AU - Kitzman, Dalane

AU - Fleg, Jerome

AU - Keteyian, Steven J.

AU - Kraus, William E.

AU - Pina, Ileana L.

AU - Whellan, David

AU - O'Connor, Christopher M.

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AB - Objectives: This study sought to examine the association between baseline beta-blocker (BB) dose and outcomes in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial. Background: Beta-blockers reduce morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction, but it is unclear whether titrating to higher BB doses improves outcomes in this setting. Methods: The HF-ACTION trial was a randomized, multicenter trial enrolling 2,331 ambulatory HF patients with systolic dysfunction (New York Heart Association functional class II to IV, left ventricular ejection fraction <0.35) randomized to exercise training versus usual care, with median follow-up of 2.5 years. The BB dose at baseline was standardized with carvedilol equivalents and analyzed as a continuous variable and by discrete dose groups. The relationship between BB dose and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints was determined before and after adjustment for variables significantly associated with outcomes in the HF-ACTION cohort. Results: Ninety-five percent of patients were receiving a BB. There was a significant inverse relationship between BB dose and all-cause death or hospitalization but not other cardiovascular endpoints after adjustment for other predictors of outcome, with a linear benefit up to the 50-mg daily dose. There was a significant association between BB dose and change in peak VO 2 at 3 months. There was no increase in bradycardia with higher doses of BB. Conclusions: There was a significant inverse relationship between BB dose and the endpoint of all-cause death or all-cause hospitalization in this well-treated HF cohort with systolic dysfunction, supporting recommendations that titrating doses up to 50 mg/day might confer a benefit in such patients.

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