Combination diuretic therapy in acute heart failure: A systematic review and meta‐analysis

Aims Current guideline recommendation to use escalating doses of loop diuretics in acute heart failure (AHF) is limited by worsening renal function and by diuretic resistance. There is an unmet need for novel therapeutic strategies to treat these patients. The aim of this study was to evaluate efficacy and safety of different combination diuretic strategies in patients with AHF. Methods and results A systematic search identified 11 eligible randomized controlled trials involving 7517 patients. A combination diuretic strategy was not associated with reduction of all‐cause death (relative risk [RR] 0.97, 95% confidence interval [CI] 0.89–1.07, p = 0.55) or heart failure (HF) events (RR 0.83, 95% CI 0.64–1.08, p = 0.16), but was associated with more weight loss (mean difference [MD]: −0.96, 95% CI −1.37 to −0.54, p < 0.0001) and diuretic efficiency (weight changes per mean daily loop diuretic dose) (MD: −0.56, 95% CI −1.11 to −0.02, p = 0.04), higher daily urinary output (MD 266.26, 95% CI 47.20–485.32, p = 0.02). Sodium–glucose co‐transporter 2 inhibitor (SGLT2i) administration during hospitalization reduced HF events (RR 0.66, 95% CI 0.58–0.76, p < 0.0001) and the risk of worsening renal function (defined as an increase >0.3 mg/dl of serum creatinine and/or a reduction >50% of the estimated glomerular filtration rate compared with baseline levels) (RR 0.69, 95% CI 0.50–0.96, p = 0.03). Conclusions In patients with AHF, a combination diuretic strategy improved early decongestion without affecting prognosis. The use of SGLT2i during index hospitalization was associated with an improvement in all‐cause mortality and HF events.