Adult Bone Marrow Cell Therapy for Ischemic Heart Disease Evidence and Insights From Randomized Controlled Trials

and tended to reduce LV end-diastolic volume (−2.26 mL; 95% confidence interval, −4.59 to 0.07; P =0.06). Similar effects were noted when data were analyzed after excluding studies with discrepancies in reporting of outcomes. The benefits also persisted when cardiac catheterization was performed in control patients as well. Although imaging modalities partly influenced the outcomes, LV ejection fraction improved in BMC-treated patients when assessed by magnetic resonance imaging. Early (<48 hours) BMC injection after myocardial Infarction was more effective in reducing infarct size, whereas BMC injection between 3 and 10 days proved superior toward improving systolic function. A minimum of 50 million BMCs seemed to be necessary, with limited additional benefits seen with increasing cell numbers. BMC therapy was safe and improved clinical outcomes, including all-cause mortality, recurrent myocardial Infarction, ventricular arrhythmia, and cerebrovascular accident during follow-up, albeit with differences between acute myocardial Infarction and chronic ischemic heart disease subgroups. Conclusions: Transplantation of adult BMCs improves LV ejection fraction, reduces infarct size, and ameliorates remodeling in patients with ischemic heart disease. These effects are upheld in the analyses of studies using magnetic resonance imaging and also after excluding studies with discrepant reporting of outcomes. BMC transplantation may also reduce the incidence of death, recurrent myocardial Infarction, ventricular arrhythmia, and cerebrovascular accident during follow-up. ( Circ Res . 2015;117:558-575. DOI: 10.1161/CIRCRESAHA.114.304792.) and results. 8 However, discrepancies in reporting of design and methods 8 may only have limited potential to influence the overall conclusions of these studies. Therefore, to delineate the effect of discrepancies on collective outcomes of cell therapy trials, we performed separate me-ta-analysis after excluding studies with discrepancies in reporting of primary outcomes, such as LVEF. Discrepancies in reporting results included incorrect calculation of effects (LVEF, infarct size, LVESV, and LVEDV) or discrepant reporting of results in different published reports in clinical trials. The results from early studies of BMC therapy as well as meta-analyses of diverse subsets of clinical trials have been discordant. We performed a systematic review and meta-analysis of pooled data from 48 randomized controlled trials of BMC therapy that enrolled 2602 patients with ischemic heart disease. Our results show that BMC injection in patients with ischemic heart disease is associated with modest yet significant improvements in left ventricular structure and function. This analysis also suggests significant improvement in left ventricular ejection fraction when magnetic resonance imaging was used to assess cardiac function. Importantly, the benefits of BMC therapy were also noted in meta-analysis performed after exclusion of studies with discrepancies in reporting of outcomes and when cardiac catheterization was performed in control patients. BMC-treated patients experienced substantive reduction in all-cause mortality, recurrent myocardial infarction, ventricular arrhythmia, and cerebrovascular accident, in-dicating significantly favorable clinical outcomes despite numerically small improvements in cardiac parameters. These results provide a robust basis for the conduct of large randomized controlled trials using patient-important clinical outcomes as primary end points.