Impact of age on implementation and tolerability of guideline-directed medical therapy in heart failure with reduced ejection fraction

Abstract

Elderly patients constitute a growing proportion of patients with heart failure with reduced ejection fraction (HFrEF), yet remain underrepresented in randomized clinical trials shaping treatment recommendations. We evaluated age-related differences in real-world contemporary HFrEF care. TITRATE-HF is a prospective, multicentre registry (June 2022-February 2024) including patients with de novo, chronic, and worsening heart failure (HF). For the current analysis HFrEF patients were categorized by age at inclusion (<65, 65–74, and ≥75 years). We assessed GDMT use, treatment patterns, side effects, and clinical outcomes (composite endpoint: first HF hospitalisation or all cause death). The cohort included 980 patients aged <65 years (29%), 1,120 patients aged 65-74 years (33%), and 1,267 patients aged ≥75 years (38%). Younger patients more frequently received GDMT, with quadruple therapy prescribed in 67.5% of those aged <65 years, 61% aged 65-74 years, and 51% aged ≥75 years (p< 0.001). In de novo HFrEF, age-related differences were observed within weeks after diagnosis, with faster and more extensive GDMT intensification in younger patients (Figure 1). Rates of treatment downgrades and the distribution of side effects were largely similar across age groups. Significant left ventricular ejection fraction improvement was observed across all age categories (all p<0.001) (Figure 2). The use of quadruple therapy at 6 months was independently associated with a lower risk of the composite endpoint between 6 and 12 months (adjusted HR 0.64, 95% CI 0.48-0.84, p= 0.001), with consistent associations across age groups (p for interaction = 0.57). Elderly patients with HFrEF received less intensive GDMT. Nevertheless, use of GDMT was associated with better clinical outcomes, also among older patients. These findings highlight the need for improved implementation strategies to optimize guideline-directed therapy and dosing levels in the ageing HFrEF population.Fig. 1.Cumulative drug changesFig 2.Median LVEF at baseline and 12m