Stem cell treatment following a heart attack

Currently the standard treatment for people suffering a heart attack (due to a blockage in the artery supplying blood to the heart) is to directly open the artery with a tiny balloon in a procedure called primary angioplasty and to introduce a small tube into the artery to keep it open called a stent. The use of primary angioplasty and stents to reopen the blocked artery can lead to a 33% reduction in the mortality (death rate) associated with this condition. Recently, bone marrow stem/progenitor cells have been investigated as a new treatment that may prevent the damage to heart muscle caused by a heart attack in addition to the treatment offered by primary angioplasty. Analysis of randomised controlled trials to 2011 indicates that this new treatment may lead to some improvements over standard treatment as measured by tests of heart function in the short and long term. Over 1,700 patients have participated so far in the 33 trials included in this systematic review.

Authors' conclusions: 

Despite the high degree of heterogeneity observed, the results of this systematic review suggest that moderate improvement in global heart function is significant and sustained long-term. However, because mortality rates after successful revascularization of the culprit arteries are very low, larger number of participants would be required to assess the full clinical effect of this treatment. Standardisation of methodology, cell dosing and cell product formulation, timing of cell transplantation and patient selection may also be required in order to reduce the substantial heterogeneity observed among the included studies.

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Background: 

Stem cell therapy offers a promising approach to the regeneration of damaged vascular and cardiac tissue after acute myocardial infarction (AMI). This has resulted in multiple randomised controlled trials (RCTs) worldwide.

Objectives: 

To critically evaluate evidence from RCTs on the effectiveness of adult bone marrow-derived stem cells (BMSC) to treat acute myocardial infarction (AMI).

Search strategy: 

This Cochrane review is an update of a previous one (published in 2008). MEDLINE (1950 to January 2011), EMBASE (1974 to January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), CINAHL (1982 to January 2011) and the Transfusion Evidence Library (1980 to January 2011) were searched. In addition, several international and ongoing trial databases were searched and handsearching of relevant conference proceedings undertaken to January 2011.

Selection criteria: 

RCTs comparing autologous stem/progenitor cells with no autologous stem/progenitor cells in patients diagnosed with AMI were eligible.

Data collection and analysis: 

Two authors independently screened all references, assessed trial quality and extracted data. Meta-analyses using a random-effects model were conducted and heterogeneity was explored for the primary outcome using sub-group analyses.

Main results: 

Thirty-three RCTs (1765 participants) were eligible for inclusion. Stem/progenitor cell treatment was not associated with statistically significant changes in the incidence of mortality (RR 0.70, 95% CI 0.40 to 1.21) or morbidity (the latter measured by re-infarction, hospital re-admission, restenosis and target vessel revascularisation). A considerably high degree of heterogeneity has been observed among the included trials. In short-term follow up, stem cell treatment was observed to improve left ventricular ejection fraction (LVEF) significantly (WMD 2.87, 95% CI 2.00 to 3.73). This improvement in LVEF was maintained over long-term follow up of 12 to 61 months (WMD 3.75, 95% CI 2.57 to 4.93). With certain measurements and at certain times, stem cell treatment was observed to reduce left ventricular end systolic and end diastolic volumes (LVESV & LVEDV) and infarct size significantly in long-term follow up. There was a positive correlation between mononuclear cell dose infused and the effect on LVEF measured by magnetic resonance imaging. A correlation between timing of stem cell treatment and effect on LVEF measured by left ventricular angiography was also observed.