Levosimendan vs. Milrinone in cardiac surgery: A GRADE-assessed systematic review and meta-analysis

BACKGROUND: Levosimendan and Milrinone are commonly used inotropic agents in patients undergoing cardiac surgery; there is a lack of evidence regarding the comparative safety and efficacy of both drugs. We aim to compare the clinical efficacy and safety of levosimendan versus Milrinone in these patients. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, Scopus, Web of Science, and Cochrane Central were searched up to November 30, 2024, for studies comparing levosimendan and Milrinone in adult and pediatric cardiac surgery patients. We used R statistical software to pool dichotomous data using odds ratio (OR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). RESULTS: Seventeen studies (15 RCTs and 2 observational) involving 890 patients were included. Across all efficacy outcomes, including cardiac index (MD 0.02, 95% CI -0.15-0.19), mean arterial pressure (MAP) (MD -0.09, 95% CI -1.97-1.79), and mPAP (mean pulmonary artery pressure) (MD -0.88, 95% CI -2.66, 0.89), no significant differences were found between the two drugs (P > 0.05). Safety outcomes, including all-cause mortality (OR 0.97, 95% CI 0.48-1.93), acute kidney injury (OR 0.89, 95% CI 0.55-1.44), and arrhythmias (OR 0.87, 95% CI 0.41-1.88), showed no statistically significant differences (P > 0.05). CONCLUSION: Levosimendan and Milrinone showed no significant differences in efficacy or safety in cardiac surgery patients. However, wide confidence intervals indicate potential clinically relevant effects. Current evidence does not favor any single agent universally, supporting individualized use based on patient phenotype and institutional practice. Further high-quality trials are needed to confirm.