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 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.