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Background: A promising approach to the treatment of chronic ischaemic heart disease (IHD) and heart failure is the use of stem cells. The last decade has seen a plethora of randomised controlled trials (RCTs) developed worldwide which have generated conflicting results., Objectives: The critical evaluation of clinical evidence on the safety and efficacy of autologous adult bone marrow-derived stem cells (BMSC) as a treatment for chronic ischaemic heart disease (IHD) and heart failure., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 3), MEDLINE (from 1950), EMBASE (from 1974), CINAHL (from 1982) and the Transfusion Evidence Library (from 1980), together with ongoing trial databases, for relevant trials up to 31st March 2013., Selection Criteria: Eligible studies included RCTs comparing autologous adult stem/progenitor cells with no autologous stem/progenitor cells in participants with chronic IHD and heart failure. Co-interventions such as primary angioplasty, surgery or administration of stem cell mobilising agents, were included where administered to treatment and control arms equally., Data Collection and Analysis: Two review authors independently screened all references for eligibility, assessed trial quality and extracted data. We undertook a quantitative evaluation of data using fixed-effect meta-analyses. We evaluated heterogeneity using the I² statistic; we explored considerable heterogeneity (I² > 75%) using a random-effects model and subgroup analyses., Main Results: We include 23 RCTs involving 1255 participants in this review. Risk of bias was generally low, with the majority of studies reporting appropriate methods of randomisation and blinding, Autologous bone marrow stem cell treatment reduced the incidence of mortality (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.14 to 0.53, P = 0.0001, 8 studies, 494 participants, low quality evidence) and rehospitalisation due to heart failure (RR 0.26, 95% CI 0.07 to 0.94, P = 0.04, 2 studies, 198 participants, low quality evidence) in the long term (≥12 months). The treatment had no clear effect on mortality (RR 0.68, 95% CI 0.32 to 1.41, P = 0.30, 21 studies, 1138 participants, low quality evidence) or rehospitalisation due to heart failure (RR 0.36, 95% CI 0.12 to 1.06, P = 0.06, 4 studies, 236 participants, low quality evidence) in the short term (< 12 months), which is compatible with benefit, no difference or harm. The treatment was also associated with a reduction in left ventricular end systolic volume (LVESV) (mean difference (MD) -14.64 ml, 95% CI -20.88 ml to -8.39 ml, P < 0.00001, 3 studies, 153 participants, moderate quality evidence) and stroke volume index (MD 6.52, 95% CI 1.51 to 11.54, P = 0.01, 2 studies, 62 participants, moderate quality evidence), and an improvement in left ventricular ejection fraction (LVEF) (MD 2.62%, 95% CI 0.50% to 4.73%, P = 0.02, 6 studies, 254 participants, moderate quality evidence), all at long-term follow-up. Overall, we observed a reduction in functional class (New York Heart Association (NYHA) class) in favour of BMSC treatment during short-term follow-up (MD -0.63, 95% CI -1.08 to -0.19, P = 0.005, 11 studies, 486 participants, moderate quality evidence) and long-term follow-up (MD -0.91, 95% CI -1.38 to -0.44, P = 0.0002, 4 studies, 196 participants, moderate quality evidence), as well as a difference in Canadian Cardiovascular Society score in favour of BMSC (MD -0.81, 95% CI -1.55 to -0.07, P = 0.03, 8 studies, 379 participants, moderate quality evidence). Of 19 trials in which adverse events were reported, adverse events relating to the BMSC treatment or procedure occurred in only four individuals. No long-term adverse events were reported. Subgroup analyses conducted for outcomes such as LVEF and NYHA class revealed that (i) route of administration, (ii) baseline LVEF, (iii) cell type, and (iv) clinical condition are important factors that may influence treatment effect., Authors' Conclusions: This systematic review and meta-analysis found moderate quality evidence that BMSC treatment improves LVEF. Unlike in trials where BMSC were administered following acute myocardial infarction (AMI), we found some evidence for a potential beneficial clinical effect in terms of mortality and performance status in the long term (after at least one year) in people who suffer from chronic IHD and heart failure, although the quality of evidence was low.

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 Methods: 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., 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.