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

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.