Cell therapy for heart disease: Trial sequential analyses of two Cochrane reviews.
Fisher SA., Doree C., Taggart DP., Mathur A., Martin-Rendon E.
Meta-analyses of cell therapy trials for heart disease have yielded discrepant results. To resolve limitations associated with meta-analyses, such as imprecision and accumulation of random errors, we conducted trial sequential analysis (TSA). Randomized controlled trials that administered autologous bone marrow-derived cells to patients who suffered acute myocardial infarction (AMI) or heart failure (HF) were included. TSA has been applied to two clinical outcomes, all-cause mortality and hospitalization for HF, and to left ventricular ejection fraction (LVEF), as a surrogate of heart function. The results suggest that there is evidence of reduction of the risk of mortality and hospitalization in HF, but insufficient evidence to determine treatment effect in AMI. Moreover, the treatment does not improve LVEF by more than a mean difference of 4% when administered to either AMI or HF patients. The required number of participants to include in a meta-analysis to detect treatment effect was also estimated.