Stem Cell Therapy Moderately Improves Cardiac Function After Acute MI

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In patients revascularized for acute myocardial infarction (MI), cardiac stem-cell therapy appears to provide moderate improvement in heart function that is sustained for up to 5 years, according to a large analysis published online February 15, 2012, in the Cochrane Library. However, the authors note a high degree of heterogeneity among studies and caution that the therapy has not been tested in large enough populations to assess its full potential.

Drawing on virtually all available databases through January 2011, Enca Martin-Rendon, MD, PhD, of John Radcliffe Hospital (Oxford, England), and colleagues analyzed data from 39 trial comparisons (33 randomized, controlled trials), involving a total of 1,765 patients with acute MI who received adult bone marrow-derived stem cells. The patients had already undergone revascularization, typically with percutaneous coronary intervention (PCI). In 26 trials, the stem cells were delivered within 7 days following the acute MI.

The review is an update of a 2008 paper that included only 13 trials.

Overall, mortality was low in all trials. Stem cell therapy resulted in a small, non-significant reductions in the incidence of short-term (15 trials reporting: RR 0.75; 95% CI 0.39-1.46; P = 0.40) or long-term mortality (6 trials reporting: RR 0.59; 95% CI 0.22-1.56; P = 0.29).

For morbidity (a composite of reinfarction, hospital readmission, restenosis, and TVR), the same non-significant result was seen between treatment and control arms for each of the individual components, regardless of short- or long-term follow up.

Cardiac Function Changes Seen

Twenty-three trials reported on left ventricular end-systolic volume. While there was no difference in mean change from baseline when measured by MRI (P = 0.71), a difference in favor of stem-cell therapy was seen when the volume was measured by left ventricular angiography (P = 0.01), SPECT (P = 0.005), and echocardiography (P < 0.0001).

Twenty-one trials reported on left ventricular end-diastolic volume. While none of these trials found a difference from baseline in the short term (< 12 months), analysis of the trials with long-term follow-up data (12 to 61 months) showed a difference in mean change from baseline in favor of stem-cell therapy when measured by left ventricular angiography (P = 0.05), SPECT (P = 0.001), and echocardiography (P = 0.0001) but again not MRI (P = 0.74).

Thirty-six trials measured left ventricular ejection fraction (LVEF). Over short-term follow-up there was a difference in mean change from baseline in favor of stem-cell therapy on MRI (P = 0.02), left ventricular angiography (P = 0.004), and SPECT (P = 0.001), but no difference on radionuclide ventriculography analysis (P = 0.71). For long-term follow-up, there was a difference on MRI, SPECT, and echocardiography.

Nine trials measured wall motion. Over short-term follow-up there was a difference in mean change in wall motion score from baseline when measured by MRI (P = 0.001). Over the long term, however, there was a difference in wall motion score from baseline when measured by echocardiography (P = 0.02) but not by MRI (P = 0.14).

Looking to the Future

Despite the addition of 20 more trials than in the 2008 review, the study authors say the individual trials are still too small to demonstrate whether the therapy has an effect on mortality and morbidity.

According to the authors, more work is needed to establish standardization of cardiac stem cell therapy, including cell dosage, timing of cell transplantation, and methods to measure cardiac function.

"The studies were hard to compare because they used so many different methods," Dr. Martin-Rendon said in a press release. “Larger trials with standardized treatment procedures would help us to know whether this treatment is really effective.”

The study authors say future trials should attempt to:

• Standardize methods and endpoints relevant to the clinical setting
• Define cell composition and standardize cell preparation and delivery
• Include patient selection as a prerequisite to treatment
• Include novel approaches such as cell or tissue engineering

Dr. Martin-Rendon and colleagues add that 13 ongoing randomized, controlled trials fulfill their criteria and will be included in future updates.

One of these is the BAMI (Bone Marrow Cells in Acute Myocardial Infarction) trial, which is expected to be the largest stem-cell therapy trial to date with over 3,000 patients.

 

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Source:
Clifford DM, Fisher SA, Brunskill SJ, et al. Stem cell treatment for acute myocardial infarction. Cochrane Library. 2012;2:CD006536.

 

 

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