The Quantitative Haemodynamic Effect of Levosimendan, Dobutamine and Milrinone in Heart Failure Patients: a Meta-Analysis

Aims: Inotropic therapy is a cornerstone of medical treatment for patients with low-output heart failure (HF). We aimed to investigate the quantitative effect of specific inotropic drugs on invasive haemodynamics. Methods: This meta-analysis assessed the haemodynamic effects of dobutamine, levosimendan, and milrinone in patients with low-output HF. Only studies using invasive haemodynamic assessment were included. The primary outcome was the quantitative change in variables such as cardiac index (CI), pulmonary artery wedge pressure (PAWP), mean pulmonary artery pressure (mPAP), mean arterial pressure (MAP), pulmonary and systemic vascular resistance (PVR and SVR) before and after administration of each drug. Quality was assessed using the National Institutes of Health Quality Assessment Tool (NIH-QAT). A sensitivity analysis compared the effect on acute versus chronic HF populations. Results: Twenty-six studies (n=1,888 patients) were included in the analyses. Based on the NIH-QAT checklist, 11 studies were at low risk of bias, 14 at moderate risk, and 1 at high risk. Meta-analysis showed that all the study drugs improved the haemodynamic variables assessed, without significant differences amongst them, except for MAP (p = 0.0486). Dobutamine and levosimendan caused a non-significant increase in MAP, while milrinone showed a trend toward a reduction in MAP (-3.46 (-7.27 to +0.35)). The heterogeneity across studies was high. In the sensitivity analysis, dobutamine improved CI more than levosimendan in patients with chronic HF. Conclusions: The use of inotropes improves haemodynamic status in patients with low-output HF, with no consistent superiority of one agent over the others. These findings support the current clinical practice of agent selection based on individual patient characteristics. Head-to-head trials in well-phenotyped HF populations are warranted to guide personalised inotrope use.