Survival benefit of guideline-directed medical therapy in older patients with heart failure: a systematic review and meta-analysis.

Abstract

Background: Heart failure-related mortality in older patients has increased. Guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF) remains insufficient in this population. This study assessed the survival benefit of GDMT in elderly patients aged ≥65 years old with HFrEF.

Methods: MEDLINE, EMBASE and Cochrane Library were searched from inception to 5 February 2025. Inclusion criteria were age ≥65 years old with HFrEF, GDMT vs no GDMT and reported survival data. Pooled prevalence, HR and risk ratio (RR) with 95% CI were analysed. Heterogeneity was further explored through subgroup analyses. We evaluated potential small-study effects using Begg's rank correlation test, Egger's regression test, funnel plot inspection and trim-and-fill analysis. Publication bias was analysed visually using a funnel plot.

Results: 34 studies with 92 916 patients from 1994 to 2024 were included. The GDMT group received three of the four main drug classes in three studies, two drug classes in four studies and at least one class in the remaining studies. There were no reported data on the survival benefits of older patients receiving four classes of GDMT. Frail older patients were less likely to receive GDMT (RR 0.63 (0.45-0.89), I2 50%, p=0.009). There was a survival benefit of GDMT in older patients with left ventricular (LV) systolic dysfunction (HR 0.69 (0.64-0.74) p<0.001, Tau² 0.03, I² 71%). Older patients receiving beta-blockers were more likely to develop bradycardia (RR 3.98 (2.72-5.82), p<0.001, I2 0%). There was no difference in hypotension, acute renal impairment and hypoglycaemia between the GDMT and control group.

Conclusions: The use of GDMT in older patients with LV systolic dysfunction was associated with a survival benefit. However, the presence of frailty may limit the successful implementation and tolerability of these therapies. High-quality studies are urgently needed to guide the development of novel strategies aimed at optimising the management of older, frail patients with LV systolic function.