Survival benefit of guideline-directed medical therapy in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

Heart failure is a major cause of mortality in the elderly and heart failure-related mortality in elderly patients has increased since 2012. The evidence of guideline-directed medical therapy (GDMT), the four pillars of treatment of heart failure with reduced ejection fraction (HFrEF), remains insufficient in this population.

The objective of this study was to assess the survival benefit of the four pillars of GDMT in elderly patients aged ≥ 65-years-old with HFrEF.

MEDLINE, EMBASE and the Cochrane Library were searched from inception to 21 July 2023. The inclusion criteria were studies comparing survival between patients ≥ 65-years-old with left ventricular systolic dysfunction receiving and not receiving GDMT. Pooled prevalence, hazard ratio (HR) and risk ratio (RR) were calculated with 95% confidence interval (CI). Heterogeneity was explored through subgroup analyses based on the number of GDMT, age cut-off, sample size, ejection fraction cut-off, study type and study publication date.

Thirty studies with 86,941 patients from 1994 to 2019 were included. The GDMT group received three drug classes in three studies, two drug classes in four studies, and at least one class in the remaining studies. There were no reported studies on elderly patients receiving four classes of GDMT. Over 5% of the elderly HFrEF patients were frail (Pooled prevelance 7%, 95%CI 2.0–14.0, I2 98%). Frail elderly patients were less likely to receive GDMT (RR 0.63, 95%CI 0.45–0.89, I2 50%, p = 0.009). There was a survival benefit of GDMT in elderly patients with HFrEF (HR 0.70, 95%CI 0.65-0.76, I2 75%, p < 0.001). Elderly patients receiving BB were more likely to develop bradycardia (RR 3.96, 95%CI 2.71-5.80, p < 0.001, I2 0%). There was no difference in the incidence of hypotension, acute renal impairment, and hypoglycemia between the GDMT and control group. The funnel plot appeared asymmetrical which suggests possible publication bias.

The use of GDMT in elderly HFrEF patients was associated with a survival benefit. Frailty may interfere with the implementation of GDMT. High quality studies are needed to guide the safety and efficacy of GDMT, and the development of guidelines on HFrEF management the in elderly according to frailty status.

Forrest plot of overall survival