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months of follow-up, the absolute improvement in LVEF in the BMC-treated group
was significantly greater compared with the placebo group [ 15 ]. Importantly, they
also reported a significant decrease in the combined endpoint of death, recurrent MI
or necessity for any revascularization in the BMC group compared with controls at
1 year [ 15 ]. This indicated that administration of BMCs was safe and provided clini-
cal benefits to patients. Contrary to these findings, the ASTAMI trial, which ran-
domized 100 patients to receive either BMC injection or standard therapy after PCI
for acute MI reported no significant benefit of BMC therapy [ 25 ]. In ASTAMI,
change in cardiac function was assessed using SPECT, echocardiography and MRI
at 6 months, which did not show any difference between cell-treated and control
patients. After 3 years, only a small difference in exercise time was noted in the
BMC group, however, without significant differences in LV functional change [ 26 ].
The differences in findings of the Repair-AMI and ASTAMI trials were attributed to
the differences in cell processing and storage [ 27 , 28 ].
Irrespective of the possible underlying reasons for differences among results
from various trials, the outcomes of cardiac repair with BMCs have been clearly
disparate. Although a large number of trials have shown multifaceted benefits with
BMC injection in patients with ischemic heart disease, several trials have failed to
show any significant improvement in cardiac parameters [ 16 , 19 , 29 ]. For example,
the FOCUS-CCTRN trial, which included 92 patients, did not find any significant
difference between the effects of BMC therapy and standard therapy on LVESV
index (LVESVI), maximal oxygen consumption, reversible defect, percentage myo-
cardial defect, total defect size, regional wall motion and clinical improvement at 6
months [ 30 ]. Similarly, the TIME trial failed to show any functional improvement
as a result of BMC injection [ 31 , 32 ]. Therefore, the efficacy of BMC therapy for
cardiac repair continues to remain somewhat uncertain in view of differences in
outcomes from small trials.
9.3 Meta-Analyses of Pooled Data from Clinical Trials
of BMC Therapy
It is estimated that nearly 80 randomized controlled trials (RCTs) of BMC therapy
for heart repair have already been completed and more than 30 are currently ongo-
ing [ 33 ]. However, each of these clinical trials has been relatively unique with
regard of cell type, cell number, cell processing technique, injection route, patient
population, follow-up duration and other trial design considerations. The interplay
of these variables makes it a challenging task to compare the results of any two
apparently similar trials. In view of these facts, we performed the first comprehen-
sive synthesis of clinical evidence in this nascent field in a systematic review and
meta-analysis in 2007 [ 16 ]. In this meta-analysis, we analyzed cumulative data from
18 clinical trials enrolling 999 patients. The results showed modest yet significant
improvements in LVEF, infarct size and LV end-systolic volume in BMC-treated
A. Samanta et al.