State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews.

Objectives: To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy.

Study Design And Setting: Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease.

Results: After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11), effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%]), and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]). No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P = 0.008) and showed more pronounced effect estimates (P = 0.002). Higher citations were associated with journal impact factor (P = 0.007), corresponding author from North America/Europe (P = 0.022), and inclusion of nonrandomized trials (P = 0.046).

Conclusions: Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.