Key result
Quadruple GDMT was prescribed less in HFrEF patients ≥75 vs <65 years (51% vs 67.5%, P<0.001), yet reduced HF hospitalization or death across all ages (HR 0.64; 95% CI 0.48-0.84).
Why the study?
Elderly patients constitute a growing proportion of the HFrEF population but remain underrepresented in randomized clinical trials that shape treatment recommendations, prompting evaluation of age-related differences in real-world contemporary HFrEF care.
Does age impact the implementation, tolerability, and clinical outcomes (first HF hospitalisation or all-cause death) of guideline-directed medical therapy in patients with HFrEF?
Cohort (n=3,367)
Yes
Does age impact the implementation, tolerability, and clinical outcomes (first HF hospitalisation or all-cause death) of guideline-directed medical therapy in patients with HFrEF?
Although elderly patients with HFrEF receive less intensive GDMT in clinical practice, quadruple therapy is similarly tolerated and independently associated with reduced mortality and heart failure hospitalization across all age groups.
Background and aims 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. Methods 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). Results 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). Conclusions 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
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Krabbe et al. (2026) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=3,367). Guideline-directed medical therapy (quadruple therapy) across age groups vs. Younger age (<65 years) or non-use of quadruple therapy was evaluated on Composite of first heart failure hospitalisation or all-cause death (adjusted HR 0.64, 95% CI 0.48-0.84, p=0.001). Quadruple GDMT was prescribed less in HFrEF patients ≥75 vs <65 years (51% vs 67.5%, P<0.001), yet reduced HF hospitalization or death across all ages (HR 0.64; 95% CI 0.48-0.84).
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