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)

Research output: Contribution to journalArticlepeer-review


Aims: Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are under-treated. The aim of this study was to evaluate the association of uptitration 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 uptitration period. We used inverse probability weighting to adjust for the likelihood of successful uptitration to determine the association of achieved dose with mortality and/or HF hospitalisation, testing for an interaction with age. Over the median follow-up of 21 months in 1,720 HFrEF patients (mean age 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: HR per 12.5% increase in dose 0.92; 95% 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 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
Number of pages10
JournalEuropean Journal of Heart Failure
Early online date25 Mar 2020
Publication statusE-pub ahead of print - 25 Mar 2020


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

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