Efficacy and safety of empagliflozin in acute heart failure: a systematic review and meta-analysis

Acute heart failure (AHF) is leading cause of hospitalization and mortality. Empagliflozin, a Sodium Glucose Co-transporter 2 inhibitor (SGLT-2i), has demonstrated benefits in HFrEF and HFpEF, but its role in AHF remains under-explored. Assess safety and efficacy of empagliflozin in AHF. A systematic review and meta-analysis adhering to PRISMA 2020 guidelines was conducted. A search on 25 February 2025, identified Phase IIb and III randomized controlled trials (RCTs) involving adults with AHF from databases like Medline®, Cochrane CENTRAL, Embase, and ClinicalTrials.gov. Outcomes included all-cause mortality, HF rehospitalization, cardiovascular deaths, and serious adverse events. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with I2 and Cochrane Q-statistic. Three RCTs (<i>n</i> = 824) were included. Empagliflozin reduced all-cause mortality (OR: 0.47, 95% CI: 0.29–0.78, <i>p</i> = 0.004) and cardiovascular death (OR: 0.56, 95% CI: 0.38–0.82, <i>p</i> = 0.003) compared to placebo. It also lowered serious adverse events risk (OR: 0.62, 95% CI: 0.44–0.87, <i>p</i> = 0.005) without significantly increasing adverse effects such as acute kidney injury, diabetic ketoacidosis, hypotension, or urinary tract infections. Sensitivity analyses confirmed these findings. Empagliflozin reduces mortality in AHF with a favorable safety profile, highlighting need for further trials. Acute heart failure (AHF) is a serious condition that causes sudden worsening of heart function, leading to hospitalizations and a high risk of death. Doctors are looking for better treatments to help patients recover safely. Empagliflozin is a medication originally used to treat diabetes, but research has shown it can help people with chronic heart failure. However, its benefits for people with acute heart failure were not clear. To find out more, we reviewed three clinical studies involving 824 patients with AHF. Our study found that patients who took empagliflozin had a lower risk of death and fewer serious health problems compared to those who did not take the medication. Importantly, empagliflozin did not cause more side effects like kidney problems, low blood pressure, or infections. These results suggest that empagliflozin could be a safe and helpful treatment for people with AHF. However, more studies are needed to confirm these findings and see how well the medication works over the long term.