Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies

The Meta-Analysis of Cell-Based Cardiac Studies (ACCRUE) consortium recently published the results of the first prospective individual patient data (IPD)–based meta-analysis that included 12 randomized clinical trials investigating 1-year outcomes in patients with recent STsegment–elevation myocardial infarction (STEMI), who received intracoronary autologous stem and progenitor cells. This IPD meta-analysis showed no effect of intracoronary autologous cell-based therapy on left ventricular function and clinical outcome in patients with recent STEMI. This contradicts some data from several smallor medium-sized singleand multicenter studies and multiple publicationbased meta-analyses involving clinical cardiac regeneration in STEMI. Although de Jong et al recently reported no difference between the cell therapy and control groups if the left ventricular parameters were measured by cardiac magnetic resonance imaging (cMRI), and the clinical end points (adverse events) were not significantly different in most of the meta-analyses, the major question is, why publication-based meta-analyses were in agreement, reporting beneficial effects of autologous reparative cell therapy in recent STEMI, but the IPD-based meta-analysis reported a negative outcome. A thorough review of the data collection, statistics, and overall principles of meta-analyses may provide some answers and useful insights to interpret current findings.