The effect of rigorous study design in the research of autologous bone marrow-derived mononuclear cell transfer in patients with acute myocardial infarction.

Introduction: Although blinding is a methodologic safeguard to ensure obtaining comparability of groups in a clinical trial, it is very difficult to maintain blinding from the beginning to the end of a study. The aim of the study was to see how proper blinding of both participants and treatment providers from the planning phase of the study to during the study affected the study outcomes.

Methods: We searched Medline, EMBASE, and Cochrane databases from inception to November 2011. The studies included in this review were randomized controlled trials, with acute myocardial infarction (AMI) patients who received percutaneous coronary intervention (PCI), intracoronary (IC) infusion of autologous bone marrow stem cells (BMSCs), unselected BMSCs, 10(8) or more cell dose, and up to 6-month follow-up periods.

Results: The initial search identified 881 references, of which 17 references were eligible for inclusion. Six of 17 trials isolated cells directly from bone marrow by aspiration in the control group as well as in the BMSC group. Nine of 17 trials underwent both cardiac catheterization and an identical injection procedure on the control group as well as the BMSC group. Compared with the control group, BMSC transplantation improved left ventricular ejection fraction (LVEF) by 2.51 (95% CI, 1.20 to 3.83; P = 0.0002; I(2) = 75%) at 6 months. In the present results, the studies that did not perform bone marrow aspiration in the control group showed significant improvement in LVEF by 3.81% (95% CI, 2.44 to 5.17), whereas no significant treatment effect was found in the studies in which the control group underwent bone marrow aspiration, as indicated the LVEF change of -1.29% (95% CI, 4.15 to 1.58). The trials that did not conduct catheterization on control subjects showed significant LVEF changes (4.45%; 95% CI, 2.48 to 6.43); however, those with cardiac catheterization as a sham procedure on the control group did not show significant changes in LVEF at 6 months (0.92%; 95% CI, -0.61 to 2.44).

Conclusions: Unblinding might be overestimating the treatment effect. These findings suggest that randomized controlled trials testing the efficacy of BMSC therapy should be appropriately designed and rigorously applied to avoid bias.