Dapagliflozin in acute heart failure management: a systematic review and meta-analysis of safety and effectiveness

Abstract

Background: Acute Heart Failure (AHF) presents as a serious pathophysiological disease with significant morbidity and mortality rates, requiring immediate medical intervention. Traditional treatment involves diuretics and vasodilators, but a subset of patients develop resistance due to acute cardiorenal syndrome. Dapagliflozin, categorized as a sodium-glucose cotransporter-2 inhibitor (SGLT2i), has emerged as a promising therapy for AHF, demonstrating substantial benefits in reducing both mortality and morbidity among patients. The purpose of this meta-analysis and systematic review is to determine dapagliflozin's safety and efficacy in AHF patients.

Methods: In accordance with PRISMA guidelines, we conducted a systematic search across several databases (PubMed, Science Direct, and Cochrane Library) up to June 2024 to identify randomized controlled trials (RCTs) that compared dapagliflozin with control treatments in patients with AHF. Key outcomes of interest included In-Hospital Cardiovascular mortality rates, duration of hospitalization, and instances of in-hospital worsening. Data extraction and quality assessment adhered to established protocols and the results were evaluated using Review Manager (RevMan Version 5.4.1) The assessment of bias risk follows the principles established in the Cochrane Handbook for Systematic Reviews and Meta-Analysis.

Results: Five RCTs comprising 912 patients met the inclusion criteria. Dapagliflozin significantly reduced In-Hospital Cardiovascular mortality (RR 0.56, 95% CI 0.36-0.88, p = 0.01, I²=26%) and 30-day hospital readmissions (RR 0.73, CI 0.54-0.99, p = 0.05, I²=7%). However, dapagliflozin did not significantly affect the length of hospital stay (MD -0.11, CI -0.73-0.51, p = 0.72, I²=60%) or the incidence of hypotension (RR 0.82, CI 0.36-1.84, p = 0.63, I²=0%). A significant weight change was observed (MD 0.93, CI 0.03-1.83, p = 0.04, I²=95%), which was resolved upon sensitivity analysis (MD 1.34, CI 1.02-1.66, p < 0.0001, I²=0%). No significant effects were found for worsening renal failure or changes in GFR in this study.

Conclusion: Dapagliflozin appears to be beneficial in reducing In-Hospital Cardiovascular mortality and 30-day hospital readmissions in AHF patients. Although it demonstrates potential, additional research is needed to establish its significance in AHF management. Further investigation with larger sample sizes, different doses, and comprehensive safety and cost-effectiveness is imperative to thoroughly evaluate the safety and clinical efficacy of Dapagliflozin, underscoring the necessity for additional data to substantiate its role in managing patients with AHF.

Clinical trial number: Not applicable.

Keywords: Acute heart failure; Dapagliflozin; In-hospital cardiovascular mortality; Meta analysis; SGLT2i.

Fig. 1

Prisma flow chart

Fig. 2

A risk of bias graph. B. risk of bias summary

Fig. 3

Forest plot of In-hospital cardiovascular mortality

Fig. 4

Forest plot of length of hospital stay in days

Fig. 5

Forest plot of 30 days hospital readmission

Fig. 6

Forest plot of change in weight from baseline in kg

Fig. 7

Forest plot of hypotension

Fig. 8

Forest plot of In hospital worsening heart failure and renal failure

Fig. 9

Forest plot of change in GFR at end of study, mL/min/1.73 m2