137patients with acute MI or chronic IHD compared with controls, who received stan-
dard treatment. BMC therapy was not associated with any significant increase in
adverse events. Similar beneficial effects of BMC therapy have since been reported
in numerous meta-analyses examining various different aspects of this novel
approach, thereby improving our understanding about the true potential of cell ther-
apy for heart repair. Indeed, systematic reviews and meta-analyses can be very use-
ful both for deciphering underlying trends that are otherwise inconspicuous, and for
identifying potential biases. However, the findings of meta-analyses may also differ
from each other, depending on the specific search criteria and inclusion and exclu-
sion criteria for each specific study. For example, results from a recent individual
patient data meta-analysis failed to identify any benefit associated with BMC ther-
apy [ 34 ]. However, this particular meta-analysis included data from only 12 trials,
whereas other large meta-analyses published to date have included data from more
than 40 BMC trials [ 19 , 29 ]. Despite these differences, large, well-conducted meta-
analyses are highly valuable toward estimating the efficacy of treatment and gener-
ating hypotheses for future clinical trials.
Our group recently published the largest meta-analysis of RCTs evaluating the
effects of BMC therapy in patients with IHD [ 19 ]. Data from 48 RCTs [ 15 , 21 , 22 ,
24 – 26 , 30 – 32 , 35 – 84 ] enrolling 2602 patients, comparing the effects of BMC injec-
tion in patients with acute MI or chronic ischemic heart disease (CIHD) were
included in this meta-analysis. In these trials, patients received BMC therapy
through intracoronary or intramyocardial routes and were followed up over time to
assess safety, efficacy and clinical outcomes. Table 9.1 summarizes the characteris-
tics of these included trials. Of note, the median sample size was 43 patients (range,
10–204 patients), median follow-up duration was 6 months (range, 3–60 months)
and median number of BMCs injected was 125 × 10^6 (range, 2 × 10^6 –60 × 10^9 ). In
patients with acute MI, the timing of BMC injection varied greatly among studies
(median 7 days after MI; range, 1–18 days). Meta-analysis of pooled data showed
that compared with standard therapy, BMC transplantation improved LVEF by
2.92%, reduced infarct size by 2.25% and reduced LVESV by 6.37 ml. There was a
trend toward reduction in LVEDV (−2.26 ml; 95% CI, −4.59 to 0.007; P = 0.06) in
BMC-treated patients. Subgroup analysis revealed that improvement in LVEF,
infarct size and LVESV persisted beyond 12 months during follow-up. Importantly,
BMC transplantation resulted in significant improvements in LVEF, infarct size and
LVESV in patients with both acute MI and CIHD. Patients benefitted from BMC
therapy regardless of their baseline LVEF, although patients with a lower LVEF at
baseline showed a greater improvement in LVESV. BMC transplantation in doses
less than 50 million was shown to be ineffective. BMC transplantation 3–10 days
after MI led to significant improvements in LVEF, LVESV and LVEDV but infarct
size was reduced only when cells were transplanted within the first 48 h after MI.
Similar findings have been reported in meta-analyses that examined the out-
comes of BMC therapy in different patient subpopulations. Delewi et al. performed
a meta-analysis of 16 trials, enrolling 1641 patients, wherein patients received
intracoronary BMC therapy following acute MI [ 85 ]. BMC therapy led to a 2.55%
increase in LVEF compared with controls. LVESVI and LVEDV index (LVEDVI)
9 Bone Marrow Cell Therapy for Ischemic Heart Disease...