Potential Benefits of Sodium-Glucose Transporter-2 Inhibitors in the Symptomatic and Functional Status of Patients With Heart Failure: A Systematic Review and Meta-Analysis

Sushen Bhalla; Yousif AlQabandi; Savitri Aninditha Nandula; Chinmayi Sree Boddepalli; Sai Dheeraj Gutlapalli; Vamsi Krishna Lavu; Rana Abdelwahab Mohamed Abdelwahab; Ruimin Huang; Shanthi Potla; Pousette Hamid

doi:10.7759/cureus.29579

September 25, 2022CureusOpen Access

Potential Benefits of Sodium-Glucose Transporter-2 Inhibitors in the Symptomatic and Functional Status of Patients With Heart Failure: A Systematic Review and Meta-Analysis

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Why the study?

To evaluate the potential benefits of SGLT-2 inhibitors on symptom burden, HRQoL, functional improvement, HHF, CVM, and ACM in patients with HF with reduced or preserved ejection fraction.

Do SGLT-2 inhibitors reduce hospitalization for heart failure or cardiovascular mortality and improve symptoms in patients with heart failure?

Structured PICO

Do SGLT-2 inhibitors reduce hospitalization for heart failure or cardiovascular mortality and improve symptoms in patients with heart failure?

P

Population

23,389 patients with heart failure (reduced or preserved ejection fraction) from 12 RCTs

I

Intervention

SGLT-2 inhibitors (empagliflozin, dapagliflozin, ertugliflozin, sotagliflozin, canagliflozin) added to standard of care

C

Comparator

Placebo added to standard of care

O

Outcome

Composite of hospitalization for heart failure or cardiovascular mortality (HHF/CVM)composite

SGLT-2 inhibitors significantly reduce the risk of hospitalization for heart failure or cardiovascular mortality and improve symptomatic status in patients with heart failure, irrespective of ejection fraction.

Implication

SGLT2 inhibitors improve HRQoL and reduce HHF/CVM/ACM across HF phenotypes; reinforces consensus from 12 pooled RCTs.

Abstract

This review evaluates the potential benefits of sodium-glucose transporter-2 (SGLT-2) inhibitors on symptom burden/health-related quality of life (HRQoL), functional improvement, hospitalization for heart failure (HHF), cardiovascular mortality (CVM), and all-cause mortality (ACM) in patients with heart failure (HF) with reduced or preserved ejection fraction (EF). We analyzed 12 randomized clinical trials (RCTs) accessed through 11 records and three secondary analyses from PubMed and Scopus following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. These studies evaluated 23,389 patients treated with either an SGLT-2 inhibitor or placebo in addition to the standard of care. Four studies recruited diabetic patients, some of whom had HF at the baseline and were evaluated as a subgroup. One study had diabetes and HF present in all patients at the baseline. Ten studies recruited patients with HF at their baseline irrespective of diabetic status. Eight studies evaluated the SGLT-2 inhibitors for a composite of hospitalization for heart failure or cardiovascular mortality (HHF/CVM) and ACM. Five of these studies showed a decreased risk for HHF/CVM, and two showed a reduced risk for ACM. One trial showed benefits in patients with heart failure with reduced ejection fraction (HFrEF) only and not in heart failure with preserved ejection fraction (HFpEF). Other studies revealed benefits but did not reach statistical significance. Ten studies assessed the SGLT-2 inhibitors for improvement in symptoms and HRQoL; four demonstrated a significant improvement, three showed a slight improvement, and three did not find any benefit. Five trials evaluated participants' functional progress by assessing for a six-minute walk test (6MWT). Two studies showed a significant increase in the distance walked by the patient, while three others did not. The SGLT-2 inhibitors reduce the risk of HHF/CVM irrespective of ejection fraction and result in a symptomatic improvement.