Levosimendan 12.5mg/5ml solution for infusion vials

ObjectivesTo evaluate the effectiveness of levosimendan in promoting weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with refractory cardiogenic shock through a meta-analysis of clinical trials.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, the Cochrane Library and Web of Science were systematically searched from inception to January 2025.Eligibility criteriaStudies were included if they were clinical trials comparing outcomes between patients receiving levosimendan and those not receiving it during VA-ECMO support. Eligible studies reported on at least one of the predefined outcomes.Data extraction and synthesisTwo independent reviewers extracted data and assessed study quality. The primary outcome was successful VA-ECMO weaning. Secondary outcomes included 30-day mortality, in-hospital mortality, duration of ECMO support and length of stay in the intensive care unit (ICU). A random-effects model was used to synthesise data and estimate pooled effect sizes, with heterogeneity assessed using the I² statistic.ResultsInvolving 2083 patients across 16 studies, levosimendan significantly improved VA-ECMO weaning success (OR=2.44, 95% CI: 1.72 to 3.48; p2=57%) compared with the control group. Additionally, it notably reduced 30-day mortality (OR=0.48, 95% CI: 0.29 to 0.81; p=0.006; I2=56%) and in-hospital mortality (OR=0.47, 95% CI: 0.26 to 0.88; p=0.02; I2=70%). Noteworthy, however, is the association of levosimendan with prolonged VA-ECMO support (days; n=1314; weighted mean difference (WMD): 2.86, 95% CI: 1.73 to 4.00; p2=60%) and extended ICU stay (days; n=629; WMD: 5.69, 95% CI: 2.19 to 9.20; p=0.001; I2=61%).ConclusionsLevosimendan improves VA-ECMO weaning success and reduces mortality. Further high-quality randomised controlled trials (RCTs) are required to confirm its clinical benefits in VA-ECMO patients. While the findings consolidate existing evidence favouring levosimendan, they also highlight residual heterogeneity and moderate-to-high risk of bias in several included studies. Therefore, future investigations, particularly well-powered RCTs with robust methodology, may help further delineate its role in specific patient populations.

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Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: -8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD -1.87; 95% CI: -2.45; -1.2) and serum lactate levels (SMD -1.63; 95% CI: -3.13; -0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection.

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BackgroundInotropes play a significant role in the treatment of cardiogenic shock (CS). Phosphodiesterase 3 inhibitors (PDE3i) are being used with increasing frequency, despite limited supporting evidence.Methods and resultsWe performed a systematic review to assess the clinical importance of PDE3i in CS. The search included studies that compared the effect of 'PDE3i with or without inotropes' with 'No PDE3i with or without inotropes' in patients with cardiogenic shock. Early death, cardiac arrest, and initiation of renal replacement therapy were assessed as outcomes. We identified 2 randomized controlled trials (RCT) with a total of 224 patients who met the eligibility requirements from the PubMed, Web of Science, and CENTRAL databases, up until October 31, 2024. One RCT compared milrinone with dobutamine (DOB), and another compared enoximone with levosimendan. Meta-analysis revealed that PDE3i were neither superior nor inferior for the outcomes in the total cohort (odds ratio [OR] 1.47, 95% confidence interval [CI] 0.35-6.26 for early deaths; OR 1.14, 95% CI 0.42-3.14 for cardiac arrest; OR 1.53, 95% CI 0.80-2.92 for the initiation of renal replacement therapy).ConclusionsThe present systematic review revealed no difference in outcomes, early deaths, cardiac arrest and initiation of renal replacement therapy when using PDE3i in patients with CS treated with or without other inotropes.

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BackgroundThe prophylactic administration of levosimendan in patients undergoing cardiac surgery remains clinically contentious, particularly regarding its efficacy and safety in improving key postoperative outcomes, such as cardiac function, renal protection, and mortality in high-risk surgical populations. Existing randomized controlled trials (RCTs) are heterogeneous in sample size, timing, and dosing of levosimendan and comparator inotropes and have yielded neutral or conflicting results for these endpoints. Moreover, prior meta-analyses have predominantly used pairwise comparisons and have not systematically compared levosimendan with all major inotropic alternatives (e.g., dobutamine, milrinone, and standard therapy) across multiple clinically relevant outcomes. As a result, the relative benefits and harms of levosimendan vs. other perioperative inotropic strategies in cardiac surgery remain unclear. To evaluate the potential benefits and risks of perioperative levosimendan therapy, we conducted a systematic network meta-analysis of available evidence.MethodsA comprehensive literature search was conducted in PubMed, Embase, the Cochrane Library, and other databases for RCTs evaluating perioperative levosimendan vs. placebo or alternative inotropic therapies, published up to 31 December 2024. Primary outcomes included cardiac index, central venous pressure (CVP), mean arterial pressure (MAP), intensive care unit (ICU) length of stay, and creatinine levels. The frequentist surface under the cumulative ranking curve (SUCRA) was calculated for each outcome to rank competing interventions.ResultsA total of 29 RCTs encompassing 4,509 patients were included. Levosimendan was associated with higher postoperative CI [standardized mean difference (SMD) 1.16, 95% CI 0.04-2.29] compared with placebo and lower postoperative MAP (SMD -0.93, 95% CI -1.62 to -0.23) compared with dobutamine. Milrinone had lower CVP compared with dobutamine (SMD -0.66, 95% CI -1.22 to -0.10) and placebo (SMD -0.46, 95% CI -0.83 to -0.09), and levosimendan (SMD 0.40, 95% CI 0.05-0.75) had higher CVP compared with milrinone. Both levosimendan (SMD -0.68, 95% CI -1.13 to -0.24) and milrinone (SMD -0.71, 95% CI -1.25 to -0.17) significantly shortened ICU stays compared with dobutamine. No significant differences in creatinine levels were identified across interventions in the network meta-analysis.ConclusionLevosimendan improved postoperative hemodynamic parameters, showing a higher cardiac index than placebo and shorter ICU stays than dobutamine, but it did not provide significant renal protection as assessed by creatinine levels.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/recorddashboard, identifier CRD42024612151.

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BackgroundAcute 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.MethodA 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.ResultIn 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.ConclusionLevosimendan 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.

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Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [-1.46-2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting.

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