Stem cell therapy after MI debated
MedWire News: Conflicting evidence has arisen concerning the use of stem cells following myocardial infarction (MI).
A small proof-of-concept study published in The Lancet has shown that autologous cardiosphere-derived cells (CDCs) reduced scar size and increased viable heart mass in patients who experienced a recent MI. However, an updated Cochrane Review has found results that suggest CDC therapy may be of no significant mortality benefit.
The prospective Cardiosphere-Derived Autologous Stem Cells to Reverse Ventricular Dysfunction (CADUCEUS) study was conducted by Eduardo Marbán (Cedars-Sinai Heart Institute, Los Angeles, California, USA) and colleagues. It enrolled 31 patients with a left ventricular ejection fraction (LVEF) of 25-45% who experienced MI in the 2-4 weeks beforehand. Of these patients, 25 were included in a per-protocol analysis.
All patients were randomly allocated in a 2:1 ratio to receive treatment with either CDCs (n=17) or standard care (n=8). Mean baseline LVEF was 39% and scar occupied a mean 24% of left ventricular mass. No complications were reported within 24 hours of CDC infusion.
At the 6-month follow-up, none of the patients in either group had died, developed cardiac tumors, or experienced major adverse cardiovascular events.
In the CDC group, four (24%) patients experienced serious adverse events, including acute MI, coronary revascularization, implantable defibrillator insertion for prophylactic indications, and noncardiac events, compared with one control patient. However, this difference was nonsignificant.
Compared with controls at 6 months, magnetic resonance imaging analysis of patients treated with CDCs showed significantly reduced scar mass (p=0.001), increased viable heart mass (p=0.01), more regional contractility (p=0.02), and more regional systolic wall thickening (p=0.015).
However, changes in end-diastolic wall volume, end-systolic volume, and LVEF did not differ significantly between the groups.
"We show intracoronary infusion of autologous CDCs after MI is safe, warranting the expansion of such therapy to phase 2 study," write the authors.
"The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes."
In a related commentary, editorialists Chung-Wah Siu and Hung-Fat Tse from the University of Hong Kong in China agree that "cardiosphere-derived cell harvesting and intracoronary delivery are feasible," but call for further research involving more patients, a longer follow-up, and a "true placebo arm."
In the updated Cochrane Review of 33 studies, autologous stem/progenitor cell treatment in recent acute MI patients was not associated with statistically significant changes in mortality or morbidity (including reinfarction, hospital readmission, restenosis, and target vessel revascularization) compared with patients who were not treated with autologous stem/progenitor cells.
However, there were significant short- and long-term (12-61 months) improvements in LVEF, at respective weighted mean differences of 2.87 and 3.75, among patients treated with stem cells.
And, "at certain measurements and certain times," stem cell treatment reduced left ventricular end systolic and diastolic volumes, and infarct size significantly in long-term follow-up.
However, there was a high degree of heterogeneity among the included trials, the authors of the review note, calling for further research to be conducted.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012
By Piriya Mahendra