Frailty Interferes with the Guideline-Directed Medical Therapy in Heart Failure Patients with Reduced Ejection Fraction

AIMS: Guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) is recommended in clinical guidelines, but elderly patients have not fully received GDMT in the clinical situation. The aim of this study was to determine the clinical characteristics of patients who have not received GDMT and the association between implementation of GDMT at discharge and physical frailty in patients with HFrEF who were hospitalized for acute decompensated heart failure (ADHF). METHODS AND RESULTS: This study was a cross-sectional study with a retrospective analysis of the Kochi YOSACOI study, a prospective multicentre observational study that enrolled 1061 patients hospitalized for ADHF from May 2017 to December 2019 in Japan. Of 339 patients (32.0%) with HFrEF, 268 patients who were assessed for physical frailty by the Japanese version of the Cardiovascular Health Study criteria were divided into two groups: those with GDMT (135 patients, 50.4%) and those without GDMT (133 patients, 49.6%). GDMT was defined as the prescription of a combination of renin-angiotensin system (RAS) inhibitors (angiotensin-converting inhibitors or angiotensin receptor blockers) and beta-blockers. The median age of patients with HFrEF was 76 years (interquartile range, 67-83 years). Patients without GDMT were older than patients with GDMT (73 years vs. 78 years, P < 0.001). Patients without GDMT tended to have more prior HF admission than did patients with GDMT (P = 0.004), and patients without GDMT had lower levels of estimated glomerular filtration rate (P < 0.001) than those in patients with GDMT. Physical frailty was observed in 54.1% of the patients without GDMT and in 38.5% of the patients with GDMT (P = 0.014). Patients without GDMT had a higher rate of cognitive impairment than that in patients with GDMT (P = 0.009). RAS inhibitors only, beta-blockers only, and both RAS inhibitors and beta-blockers were less frequently prescribed in patients with physical frailty than in patients with physical non-frailty (52.0% vs. 86.7%, P < 0.05; 70.1% vs. 100.0%, P < 0.05; 42.5% vs. 86.7%, P < 0.01, respectively). In logistic regression analysis, compared with physical non-frailty, physical frailty was significantly associated with no implementation of GDMT (odds ratio: 6.900, 95% confidence interval: 1.420-33.600; P = 0.017), independent of older age and severe renal dysfunction. CONCLUSIONS: The results of this study suggest that physical frailty is one of the factors that may withhold GDMT in patients with HFrEF.