Key result
Adding SGLT2 inhibitors to loop diuretics cuts AHF mortality ~40% and reduces worsening heart failure.
Why the study?
Does add-on pharmacotherapy (SGLT2 inhibitors, tolvaptan, or hydrochlorothiazide) to loop diuretics improve outcomes in adults hospitalized with acute heart failure?
Meta-Analysis
Does add-on pharmacotherapy (SGLT2 inhibitors, tolvaptan, or hydrochlorothiazide) to loop diuretics improve outcomes in adults hospitalized with acute heart failure?
Relative Risk: 0.6 (95% CI 0.38–0.94)
In acute heart failure, adding SGLT2 inhibitors to loop diuretics reduces mortality and worsening heart failure, whereas adding hydrochlorothiazide improves decongestion and shortens length of stay at the cost of increased renal dysfunction and hypokalemia.
Supports adding SGLT2 inhibitors to loop diuretics in acute HF; extends chronic HF benefits to hospitalized patients.
Many patients hospitalized with acute heart failure (AHF) do not respond adequately to initial intravenous loop diuretic therapy, and residual congestion at discharge is associated with adverse outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials comparing loop diuretics alone versus loop diuretics in combination with add-on pharmacotherapy in adults hospitalized with AHF. PubMed, Embase, and CENTRAL were searched from inception to May 7, 2025. Efficacy outcomes included mortality, hospital readmission, hospital length of stay (LOS), change in body weight, and urine output (UO). Safety outcomes included worsening renal function, worsening heart failure (WHF), hypokalemia, and serious adverse events. Twenty-four randomized studies were identified, with 22 included in the meta-analysis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduced mortality [risk ratio (RR), 0.60 (95% confidence interval [CI], 0.38–0.94)], WHF [RR, 0.64 (95% CI, 0.43–0.96)], serious adverse events [RR, 0.74 (95% CI, 0.60–0.92)], and body weight [mean difference (MD), −1.05 (95% CI, −1.97 to −0.13) kg]. Tolvaptan was associated with greater weight reduction [MD, −0.98 (95% CI, −1.25 to −0.70) kg] and increased UO [MD, 1.15 (95% CI, 0.16–2.14) L]. Add-on hydrochlorothiazide (HCTZ) increased UO [MD, 0.95 (95% CI, 0.47–1.43) L] and decreased LOS [MD, −1.38 (95% CI, −2.40 to −0.36) days] but increased the risk of worsening renal function [RR, 2.03 (95% CI, 1.10–3.74)] and hypokalemia [RR, 2.31 (95% CI, 1.51–3.52)]. Overall, the combination with SGLT2 inhibitors, tolvaptan, and HCTZ improved surrogate markers of decongestion in AHF. SGLT2 inhibitors were associated with reduced mortality and WHF, whereas HCTZ shortened hospital LOS but increased the risk of renal dysfunction and hypokalemia.
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Leaman et al. (2026) conducted a meta-analysis in Acute heart failure. Add-on pharmacotherapy (SGLT2 inhibitors, tolvaptan, or hydrochlorothiazide) vs. Loop diuretics alone was evaluated on Mortality (with SGLT2 inhibitors) (RR 0.60, 95% CI 0.38-0.94). Adding SGLT2 inhibitors to loop diuretics in acute heart failure significantly reduced mortality (RR 0.60; 95% CI 0.38-0.94) and worsening heart failure.