Effect of Inotropes in Patients with Advanced Heart Failure: A Meta-Analysis of Randomized Trials

Advanced heart failure (AHF) is associated with high morbidity and mortality. Inotropic agents such as dobutamine, levosimendan, and milrinone are commonly used to improve cardiac output, but their impact on mortality remains controversial due to limited head-to-head comparisons.

To compare the effectiveness of inotropes (dobutamine, levosimendan, milrinone) versus placebo or each other in reducing mortality in patients with AHF.

This systematic review and meta-analysis followed PRISMA guidelines and was registered with PROSPERO (CRD42024584389). We searched Scopus, CENTRAL, Google Scholar, PubMed, and clinical trial registries up to December 2024 for randomized controlled trials (RCTs) published from 2000 onward. Eligible studies included adults (≥18 years) with AHF and cardiorenal syndrome. Risk differences (RD) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with the Cochrane Q-test, Tau², and I². Subgroup analyses and meta-regression were performed. Publication bias was evaluated using funnel plots and Duval and Tweedie's trim-and-fill method.

Twenty-four RCTs involving 2,862 participants were included. The pooled RD for mortality was -0.023 (95% CI: -0.046 to 0.000; p=0.055), indicating no significant difference. Subgroup analysis by control (inotropes vs. placebo) showed similar non-significant results. Meta-regression for moderators (age, LVEF, systolic blood pressure) did not explain heterogeneity. The funnel plot suggested asymmetry, indicating potential publication bias.

Inotropic agents showed a non-significant trend toward reduced mortality in AHF patients. Heterogeneity limits firm conclusions. Larger RCTs are needed to identify subgroups that may benefit.