Review question: Are bone marrow cells safe and effective as a treatment following a heart attack?
Background: Currently the standard treatment for people suffering a heart attack (due to a blockage in the artery supplying blood to the heart) is direct opening of the artery with a tiny balloon in a procedure called primary angioplasty and introduction of a small tube (called a stent) into the artery to keep it open. The use of primary angioplasty and stents to reopen the blocked artery can lead to a 35% reduction in the mortality (death rate) associated with this condition. In recent years, bone marrow stem/progenitor cells have been investigated as a potential treatment. They may prevent the damage to the heart muscle caused by a heart attack, when used in addition to the treatment offered by primary angioplasty and standard medical therapy.
Study characteristics: Randomised trials comparing bone marrow-derived cells with no cells in patients diagnosed with acute myocardial infarction were eligible for this review. We searched databases to March 2015. This review was supported by the National Institute of Health Research (NIHR) through its Cochrane Incentive Award programme.
Key results: In this updated systematic review we analysed data from a total of 41 trials with over 2700 patients. Evaluation of the currently available evidence indicates that this treatment may not lead to improvement when compared to standard treatment, as measured by the frequency of deaths, heart attacks and/or heart failure requiring re-hospitalisation following treatment, as well as tests of heart function, in the short and long term.
Quality of evidence for primary outcomes: The evidence in this review is of moderate quality due to the small number of events.
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.
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.
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.
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.
RCTs comparing autologous bone marrow-derived cells with no cells in patients diagnosed with AMI were eligible.
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.
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.