title: Stem cell treatment for acute myocardial infarction.
abstract: BACKGROUND
  Cell transplantation offers a potential therapeutic approach to the repair and regeneration of damaged vascular and cardiac tissue after acute myocardial infarction (AMI). This has resulted in multiple randomised controlled trials (RCTs) across the world.
  
  
  OBJECTIVE
  To determine the safety and efficacy of autologous adult bone marrow stem cells as a treatment for acute myocardial infarction (AMI), focusing on clinical outcomes.
  
  
  METHODS
  This Cochrane review is an update of a previous version (published in 2012). We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 2), MEDLINE (1950 to March 2015), EMBASE (1974 to March 2015), CINAHL (1982 to March 2015) and the Transfusion Evidence Library (1980 to March 2015). In addition, we searched several international and ongoing trial databases in March 2015 and handsearched relevant conference proceedings to January 2011.
  
  
  METHODS
  RCTs comparing autologous bone marrow-derived cells with no cells in patients diagnosed with AMI were eligible.
  
  
  METHODS
  Two review authors independently screened all references, assessed the risk of bias of the included trials and extracted data. We conducted meta-analyses using random-effects models throughout. We analysed outcomes at short-term (less than 12 months) and long-term (12 months or more) follow-up. Dichotomous outcomes are reported as risk ratio (RR) and continuous outcomes are reported as mean difference (MD) or standardised MD (SMD). We performed sensitivity analyses to evaluate the results in the context of the risk of selection, performance and attrition bias. Exploratory subgroup analysis investigated the effects of baseline cardiac function (left ventricular ejection fraction, LVEF) and cell dose, type and timing of administration, as well as the use of heparin in the final cell solution.
  
  
  RESULTS
  Forty-one RCTs with a total of 2732 participants (1564 cell therapy, 1168 controls) were eligible for inclusion. Cell treatment was not associated with any changes in the risk of all-cause mortality (34/538 versus 32/458; RR 0.93, 95% CI 0.58 to 1.50; 996 participants; 14 studies; moderate quality evidence), cardiovascular mortality (23/277 versus 18/250; RR 1.04, 95% CI 0.54 to 1.99; 527 participants; nine studies; moderate quality evidence) or a composite measure of mortality, reinfarction and re-hospitalisation for heart failure (24/262 versus 33/235; RR 0.63, 95% CI 0.36 to 1.10; 497 participants; six studies; moderate quality evidence) at long-term follow-up. Statistical heterogeneity was low (I(2) = 0% to 12%). Serious periprocedural adverse events were rare and were generally unlikely to be related to cell therapy. Additionally, cell therapy had no effect on morbidity, quality of life/performance or LVEF measured by magnetic resonance imaging. Meta-analyses of LVEF measured by echocardiography, single photon emission computed tomography and left ventricular angiography showed evidence of differences in mean LVEF between treatment groups although the mean differences ranged between 2% and 5%, which are accepted not to be clinically relevant. Results were robust to the risk of selection, performance and attrition bias from individual studies.
  
  
  CONCLUSIONS
  The results of this review suggest that there is insufficient evidence for a beneficial effect of cell therapy for AMI patients. However, most of the evidence comes from small trials that showed no difference in clinically relevant outcomes. Further adequately powered trials are needed and until then the efficacy of this intervention remains unproven.
authors.affiliation: Systematic Review Initiative, NHS Blood and Transplant, Level 2, John Radcliffe Hospital, Headington, Oxford, Oxon, UK, OX3 9BQ.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Huajun
authors.initials: H
authors.lastname: Zhang
authors.forename: Carolyn
authors.initials: C
authors.lastname: Doree
authors.forename: Anthony
authors.initials: A
authors.lastname: Mathur
authors.forename: Enca
authors.initials: E
authors.lastname: Martin-Rendon
mesh_terms: D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D009203:Myocardial Infarction / Q000401:mortality / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013318:Stroke Volume / Q000502:physiology