Heart failure treatment up‐titration and outcome and age: an analysis of BIOSTAT‐CHF

Ify R. Mordi, Wouter Ouwerkerk, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Marco Metra, Leong L. Ng, Nilesh J. Samani, Dirk J. van Veldhuisen, Faiez Zannad, Adriaan A. Voors, Chim C. Lang (Lead / Corresponding author)

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Aims: Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up-titration of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta-blockers on outcome across the age spectrum in HFrEF patients. Methods and results: We analysed HFrEF patients on sub-optimal doses of ACEI/ARB and/or beta-blockers from the BIOSTAT-CHF study stratified by age. Patients underwent a 3-month up-titration period. We used inverse probability weighting to adjust for the likelihood of successful up-titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow-up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta-blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI-ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91–0.94, P < 0.001; beta-blocker: HR 0.98, 95% CI 0.95–1.00, P = 0.046], with a significant interaction with age seen for beta-blockers but not ACEI/ARB (P = 0.034 and P = 0.22, respectively). Conclusions: Achieving higher doses of ACEI/ARB was associated with improved outcome regardless of age. However, achieving higher doses of beta-blockers was only associated with improved outcome in younger, but not in older patients.

Original languageEnglish
Pages (from-to)436-444
Number of pages9
JournalEuropean Journal of Heart Failure
Issue number3
Early online date25 Mar 2020
Publication statusPublished - Mar 2021


  • ACE Inhibitor
  • Angiotensin receptor blocker
  • Beta-blocker
  • Up-titration
  • Elderly

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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