Stem cells for treatment of cardiovascular diseases: An umbrella review of randomized controlled trials

Aims: Stem cells are a promising therapy for various medical conditions. The literature regarding their adoption for the clinical care of cardiovascular diseases (CVD) is still conflicting. Therefore, our aim is to assess the strength and credibility of the evidence on clinical outcomes and application of stem cells derived from systematic reviews and meta-analyses of intervention studies in CVD. Methods and results: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For meta-analyses of RCTs, outcomes with a randomeffect p-value <0.05, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment was used, classifying the evidence from very low to high. From 184 abstracts initially identified, 11 meta-analyses (for a total of 34 outcomes) were included. Half of the outcomes were statistically significant (p < 0.05), indicating that stem cells are more useful than placebo. High certainty of evidence supports the associations of the use of stem cells with a better left ventricular end systolic volume and left ventricular ejection fraction (LVEF) in acute myocardial infarction; improved exercise time in refractory angina; a significant lower risk of amputation rate in critical limb ischemia; a higher successful rate in complete healing in case of lower extremities ulcer; and better values of LVEF in systolic heart failure, as compared to placebo. Conclusion and relevance: The adoption of stem cells in clinical practice is supported by a high certainty of strength in different CVD, with the highest strength in acute myocardial infarction and refractory angina.