Systematic Review and Meta-Analysis of Stem Cell Therapy in Myocardial Infarction: Effects on Left Ventricular Ejection Fraction and Major Adverse Cardiovascular Events

Introduction Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide, often progressing to heart failure (HF) despite advances in treatment. Stem cell therapy has emerged as a promising approach to repair myocardial tissue, improve cardiac function, and reduce the progression to HF. However, the long-term efficacy and clinical outcomes remain uncertain. This systematic review and meta-analysis aimed to evaluate the mid-to long-term effects of stem cell therapy on left ventricular ejection fraction (LVEF), infarct size, and major adverse cardiovascular events (MACE) in AMI patients. Methods A comprehensive search was conducted across PubMed, Scopus, Embase, and CENTRAL databases, up to August 2025, following PRISMA guidelines. The study included randomized controlled trials (RCTs) that assessed the effects of stem cell therapy on LVEF and MACE. Data extraction was performed independently by two reviewers, and risk of bias was assessed using Cochrane’s Risk of Bias 2.0 tool. Statistical analyses were performed using Stata 18.0, with heterogeneity quantified using I², and publication bias assessed through funnel plots. Results A total of 83 studies involving 7307 patients were included in the analysis. The average age of the patients was 55.29 ± 12 years, with a follow-up duration of 27.5 days. Significant improvements in LVEF were observed at various time points: 1.83% at 6 months, 2.21% at 12 months, and 2.21% at 24 months. The highest mean difference in LVEF was observed in Wang et al. (2014) with a mean difference (MD) of 17.60%, while the lowest was −4.20% in Wohrle et al. (2010). MACE analysis showed a favorable trend at 6 months with an odds ratio of −0.89 (95% CI: −1.14; −0.63), but no significant improvement at 12, 24, or 36 months. A reduction in infarct size was noted at 6 months (MD: 1.80%, 95% CI: 0.58; 3.02), but this was minimal at 12 months (MD: 0.70%, 95% CI: 0.48; 0.91). Conclusion Stem cell therapy shows promise for improving LVEF and reducing infarct size in the short to mid-term after AMI. However, long-term benefits remain inconclusive, with minimal effects observed at 24 and 36 months. Further studies are required to determine the optimal timing, dosage, and stem cell source to maximize therapeutic efficacy. Additionally, the use of major adverse cardiovascular events (MACE) as a primary endpoint may provide a more comprehensive assessment of the long-term impact of stem cell therapy in AMI patients.