Protocolized natriuresis-guided diuretic therapy in acute heart failure: a systematic review and meta-analysis.

backgroundVolume overload is the primary pathophysiological mechanism underlying signs and symptoms in acute heart failure (AHF). However, evidence-based strategies for optimal loop diuretic dosing and monitoring remain limited. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of natriuresis-guided protocols for titrating diuretic therapy in patients with AHF.

methodsWe searched Cochrane, PubMed, and Embase databases for studies that compared natriuresis-guided diuretic therapy versus standard management in patients with AHF from their inception until June 2025. We computed pooled risk ratio (RR) for binary outcomes, and for continuous outcomes, we calculated either pooled mean difference (MD) or geometric mean ratio (GMR) derived from differences in log-means, all with 95% confidence intervals (CIs). Data from the studies were pooled using R version 4.4.1. Risk of bias was assessed using RoB 2 and ROBINS-I tools. We also performed a sensitivity analysis restricted to randomized controlled trials (RCTs).

resultsThree RCTs and two observational studies were included, encompassing 933 patients, of which 404 (43%) were in the natriuresis-guided therapy group. Protocolized therapy significantly increased natriuresis (GMR: 1.30; 95% CI: 1.14 to 1.49) and diuresis (GMR: 1.21; 95% CI: 1.09 to 1.35) after 48 h. No significant differences were observed in weight loss, length of hospital stay, heart failure rehospitalization, or all-cause mortality. Protocolized therapy was associated with a lower risk of doubling serum creatinine (RR: 0.52; 95% CI: 0.28 to 0.98), without increasing the risk of hypokalemia or hypotension. Two RCTs were deemed at "low" risk of bias by the RoB 2 tool, while Bayat et al. was rated as having "some concerns." For studies assessed using the ROBINS-I tool, the ENACT-HF study presented a "moderate" risk of bias, and Pellegrino et al. a "serious" risk. Nevertheless, our sensitivity analysis, limited to RCTs, confirmed our findings for all efficacy and safety endpoints.

conclusionIn this meta-analysis of patients with AHF, protocolized natriuresis-guided therapy was safe and associated with improved diuresis and natriuresis after 48 h, as well as a reduced risk of acute kidney injury. While the short-term safety and efficacy are promising, further large RCTs are needed to evaluate the effects on clinical endpoints in diverse healthcare settings and patients worldwide.