Objectives To 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.

Design Systematic review and meta-analysis.

Data sources PubMed, Embase, the Cochrane Library and Web of Science were systematically searched from inception to January 2025.

Eligibility criteria Studies 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 synthesis Two 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.

Results Involving 2083 patients across 16 studies, levosimendan significantly improved VA-ECMO weaning success (OR=2.44, 95% CI: 1.72 to 3.48; p<0.00001; I²=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; p<0.00001; I²=60%) and extended ICU stay (days; n=629; WMD: 5.69, 95% CI: 2.19 to 9.20; p=0.001; I²=61%).

Conclusions Levosimendan 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.