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Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial.

Publication ,  Journal Article
Pierce, JB; Mentz, RJ; Sun, J-L; Alhanti, B; Whellan, DJ; Kraus, WE; Piña, IL; Fiuzat, M; O'Connor, CM; Greene, SJ
Published in: Am Heart J
September 2022

BACKGROUND: Clinical guidelines recommend titration of angiotensin converting enzyme inhibitors (ACEi) and beta-blockers among patients with heart failure with reduced ejection fraction (HFrEF) to maximally tolerated doses. Patient characteristics associated with dose titration and clinical outcomes subsequent to dose titration remain poorly characterized. METHODS: Among 1999 ambulatory patients with chronic HFrEF in the HF-ACTION trial, use and dosing of ACEi and evidence-based beta-blockers were examined at baseline and 6-month follow-up. Multivariable logistic regression models were used to assess factors associated with dose escalation (medication initation or dosing increase) or dose de-escalation (medication discontinuation or dosing decrease). Cox proportional hazard regression models were used to examine associations between dose trajectory group (stable target, stable sub-target, dose escalation, and dose de-escalation) and subsequent mortality and hospitalization outcomes. RESULTS: For both ACEi and beta-blockers, hospitalization for heart failure in the 6 months prior to enrollment (odds ratio [OR] 2.32 [95% confidence interval 1.58-3.42]) for ACEi; 1.42 [1.05-1.9] for beta-blockers) and higher systolic blood pressure (OR 1.01 [1.00-1.03] per 1 mmHg increase for ACEi; 1.01 [1.00-1.02] for beta-blockers) were associated with dose escalation. Hospitalization 6 months prior to enrollment for any cause (including HF or non-HF causes) was associated with dose de-escalation (OR 1.60 [1.14-2.25] for ACEi; 1.67 [1.20-2.33] for beta-blockers). After adjustment for patient characteristics, compared with stable target dosing, dose de-escalation of either medication was associated with greater all-cause mortality (adjusted hazard ratio [aHR] 1.64 [1.11-2.42] for ACEi; 1.62 [1.04-2.53] for beta-blockers). Compared with stable target dosing, both dose de-escalation (aHR 1.98 [1.36-2.87]) and stable sub-target dosing (aHR 1.49 [1.18-1.87]) of beta-blockers were associated with greater cardiovascular mortality or hospitalization for heart failure. CONCLUSIONS: Among outpatients with chronic HFrEF, patient characteristics including recent hospitalization status and blood pressure were associated with odds of subsequent escalation and de-escalation of ACEi and beta-blocker therapy. Compared with patients receiving guildeline-recommended target doses, dose de-escalation of either medication and sub-target dosing of beta-blockers were associated with greater morbidity and mortality over long-term follow-up.

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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

September 2022

Volume

251

Start / End Page

115 / 126

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Stroke Volume
  • Humans
  • Hospitalization
  • Heart Failure
  • Cardiovascular System & Hematology
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Adrenergic beta-Antagonists
  • 3201 Cardiovascular medicine and haematology
 

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Pierce, J. B., Mentz, R. J., Sun, J.-L., Alhanti, B., Whellan, D. J., Kraus, W. E., … Greene, S. J. (2022). Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial. Am Heart J, 251, 115–126. https://doi.org/10.1016/j.ahj.2022.05.018
Pierce, Jacob B., Robert J. Mentz, Jie-Lena Sun, Brooke Alhanti, David J. Whellan, William E. Kraus, Ileana L. Piña, Mona Fiuzat, Christopher M. O’Connor, and Stephen J. Greene. “Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial.Am Heart J 251 (September 2022): 115–26. https://doi.org/10.1016/j.ahj.2022.05.018.
Pierce JB, Mentz RJ, Sun J-L, Alhanti B, Whellan DJ, Kraus WE, et al. Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial. Am Heart J. 2022 Sep;251:115–26.
Pierce, Jacob B., et al. “Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial.Am Heart J, vol. 251, Sept. 2022, pp. 115–26. Pubmed, doi:10.1016/j.ahj.2022.05.018.
Pierce JB, Mentz RJ, Sun J-L, Alhanti B, Whellan DJ, Kraus WE, Piña IL, Fiuzat M, O’Connor CM, Greene SJ. Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial. Am Heart J. 2022 Sep;251:115–126.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

September 2022

Volume

251

Start / End Page

115 / 126

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Stroke Volume
  • Humans
  • Hospitalization
  • Heart Failure
  • Cardiovascular System & Hematology
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Adrenergic beta-Antagonists
  • 3201 Cardiovascular medicine and haematology