Does initiating SGLT2 inhibitors at an early stage of heart failure admission really reduce cardiovascular mortality and first rehospitalization? A meta-analysis of randomized controlled trials

Background Acute heart failure (HF) patients are at high risk, especially in the first three months following discharge, when rehospitalizations are 30% common and mortality can be close to 10%. Although sodium-glucose cotransporter-2 (SGLT2) inhibitors are essential for treating heart failure, their benefit when initiated during acute decompensation remains uncertain. Purpose To evaluate the effect of early administration of SGLT2 inhibitors in hospitalized patients for cardiovascular (CV) death and HF rehospitalization, we conducted a meta-analysis of six randomized controlled trials. Methods We conducted a systematic search of PubMed, Embase, Scopus, and the Cochrane Library through May 2025 to identify randomized controlled trials comparing initiation of SGLT2 inhibitors during or immediately following an acute HF admission versus placebo. Three trials (SOLOIST WHF, DICTATE AHF, EMPULSE) with a total of 1,986 patients met inclusion criteria. The primary composite endpoint was CV death or first HF rehospitalization. Using RevMan 5.4, we pooled risk ratios (RRs) and 95% confidence intervals (CIs) via Mantel-Haenszel methods. Heterogeneity was evaluated by Higgins’ I, with a random or fixed effects model applied accordingly. Statistical significance was defined as p < 0.05. Risk of bias was assessed using the RoB 2.0 tool. Results Pooled results demonstrated suggestive but borderline benefits for mortality and composite outcomes while showing no statistically significant reductions in rehospitalization or worsening heart failure alone: worsening heart failure events yielded a risk ratio (RR) of 0.89 (95% CI 0.71–1.13; p=0.34), all-cause 30/60-day readmission an RR of 0.83 (95% CI 0.46–1.49; p=0.54), heart failure events an RR of 0.72 (95% CI 0.48–1.09; p=0.12), and overall hospital readmission an RR of 0.86 (95% CI 0.65–1.12; p=0.26). In contrast, the composite of cardiovascular death or hospitalizations showed a borderline significant reduction (RR 0.48, 95% CI 0.23–0.99; p=0.05), albeit with high heterogeneity (I²=95%), and the composite of heart failure–related or cardiovascular death demonstrated a consistent borderline benefit (RR 0.77, 95% CI 0.60–1.00; p=0.05; I²=0%). These findings collectively address the 20–30% early-event risk highlighted in the introduction, supporting the potential clinical value of early SGLT2 inhibition for reducing cardiovascular death and combined death/hospitalization risks despite modest or non-significant effects on rehospitalization alone, with low-to-moderate heterogeneity in most non-composite endpoints. Conclusions Initiating SGLT2 inhibitors during or immediately after acute HF admission confers a significant reduction in CV death or first HF rehospitalization. These findings support early post-decompensation initiation ideally before or at discharge as a strategy to improve outcomes and inform future AHA performance measures for acute HF care.