Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies: Controversies in Meta-Analyses Results on Cardiac Cell-Based Regenerative Studies

Abstract

In contrast to multiple publication-based meta-analyses involving clinical cardiac regeneration therapy in patients with recent myocardial infarction, a recently published meta-analysis based on individual patient data reported no effect of cell therapy on left ventricular function or clinical outcome. A comprehensive review of the data collection, statistics, and the overall principles of meta-analyses provides further clarification and explanation for this controversy. The advantages and pitfalls of different types of meta-analyses are reviewed here. Each meta-analysis approach has a place when pivotal clinical trials are lacking and sheds light on the magnitude of the treatment in a complex healthcare field.

Keywords: heart failure; meta-analysis; myocardial infarction; outcome measures; stem cells.

Figure 1. Association between the number of patients (sample size) and weighted mean difference in the left ventricular ejection fraction (EF) between cell-based treatment and controls in meta-analyses of intracoronary cell therapy in patients with recent acute myocardial infarction

A, Sample size (blue columns) and changes in EF from baseline to follow-up (differences between cell-treated and controls) (red columns). B, Correlation between sample size and mean difference in EF between cell-based treatment and control groups.

Figure 2. Increased ejection fraction (EF) under standard medical treatment for acute myocardial infarction (AMI)

Note that the lower the baseline EF at randomization/cell treatment, the higher the increase in EF at the 1-year follow-up. (Adapted from Engblom et al.)

Figure 3. Schematic of a forest plot statistic for calculation of the mean difference in a continuous parameter between the treated and control groups

Note that a 10-fold larger study has less weight in the final results due to a larger standard deviation (SD).