Comparative safety and efficacy of levosimendan versus dobutamine in acute heart failure: a systematic review, meta-analysis, and meta-regression

Background: Acute heart failure (AHF) remains a major cause of morbidity and mortality, especially in hospitalized patients. Inotropic agents like dobutamine have long been used for hemodynamic support, yet concerns over adverse effects such as arrhythmias and increased myocardial oxygen consumption limit their safety. Levosimendan, a calcium sensitizer with vasodilatory properties, offers a potential alternative. This meta-analysis was conducted to evaluate the comparative safety and efficacy of levosimendan versus dobutamine in patients with AHF. Method: A systematic review and meta-analysis was conducted following PRISMA and AMSTAR 2 guidelines. Major databases including PubMed, Cochrane, Embase, and ScienceDirect were searched up to July 2025 without any language restrictions. Sixteen studies including 15 randomized controlled trials and 1 cohort study were evaluated for this study. Outcomes were pooled using a random effects model. Meta-regression was performed to assess the influence of baseline covariates. Result: In the pooled analysis of 16 studies, levosimendan showed a statistically significant reduction in mortality (RR: 0.59; P = 0.0009) compared to dobutamine. While systolic blood pressure and diastolic blood pressure remained comparable, levosimendan led to a marked reduction in pulmonary capillary wedge pressure and improved cardiac index, left ventricular ejection fraction, and mixed venous oxygen saturation. B-type natriuretic peptide and IL-6 levels also declined significantly in the levosimendan group. Adverse events such as hypotension and atrial fibrillation were slightly more frequent with levosimendan, while tachycardia and ischemic events were more common with dobutamine. Overall adverse event rates were similar. Conclusion: Levosimendan demonstrates favorable effects on mortality and key hemodynamic parameters in patients with AHF, especially those on β-blockers or with impaired left ventricular function. Although certain adverse effects like hypotension were more frequent, the overall safety profile remained comparable to dobutamine. These findings suggest levosimendan as a safer and more effective alternative in selected high-risk heart failure populations.