Key messages
- Stem cell treatment does not lead to an improvement in clinical outcomes in people that have had a heart attack.
- The therapy leads to few unwanted or harmful (adverse) effects around the time of treatment.
What is the health problem?
Heart attacks are caused by a blockage in an artery supplying blood to the heart muscle. Although new therapies are advancing, many people who have had a heart attack have a reduction in cardiac function and decreased life expectancy.
How is the condition treated?
Currently, the standard treatment for people who suffer a heart attack is the re-opening of the blocked artery with a tiny balloon in a procedure called primary angioplasty, and the introduction of a small tube (called a stent) into the artery to keep it open.
What is the treatment under study?
Bone marrow-derived cells have been investigated as an additional treatment for heart attacks based on their ability to repair damaged heart muscle. This has shown a beneficial effect on outcomes such as chemicals in the blood that correlate to heart damage and imaging tests that measure heart function. However, it has not been proven to affect important clinical outcomes like death, repeat readmissions to hospital or the chance of having another major heart problem (e.g. a stroke or another heart attack).
What did we want to find out?
We wanted to know if stem cell treatment results in a reduction in death and improvement in measures of heart function when the data from all studies performed are combined.
What did we do?
This review identified clinical trials that randomised people diagnosed with a heart attack to either cell treatment, a placebo (a 'dummy' treatment) or to continue on standard medical therapy alone. In order to identify these trials, we searched databases for relevant clinical trials up to February 2022. After the inclusion of these trials, we analysed the data to find common trends. We also analysed the risk of bias (including the possibility that people in the studies were aware of which treatment they were getting).
What did we find?
In this review we selected and analysed data from 53 trials that recruited 4159 people. We are confident that this review shows that stem cell treatment does not lead to an improvement in clinical outcomes in people that have had a heart attack. The therapy led to few unwanted or harmful (adverse) effects around the time of treatment.
What are the limitations of the evidence?
It is possible that people in some of the studies were unintentionally aware of which treatment they were getting. Not all studies provided data about everything that we wished to include in our analysis.
How up-to-date is this evidence?
The evidence in this review is up-to-date to February 2022.
There is evidence that when autologous bone marrow-derived cells are administered to patients who have undergone primary angioplasty following AMI, mortality is not reduced. However, the number of events is very low, so any difference observed between treatments would be small. We do not expect that future trials in line with this review will change the outcomes, therefore new clinical trials may wish to focus on other strategies or patient populations.
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-derived stem cells as a treatment for AMI, focusing on clinical outcomes.
This Cochrane review is an update of a previous version (published in 2015). We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 2), MEDLINE, EMBASE, CINAHL, LILACS and CPCI-S to February 2022. In addition, we searched the ClinicalTrials.gov and World Health Organization (WHO) ICTRP databases in January 2023. We also searched the references of relevant recent reviews and meta-analyses.
RCTs that compared autologous bone marrow-derived cells to no cells (either placebo or optimal standard of care) in patients diagnosed with AMI were eligible.
Two review authors independently screened all references, assessed the risk of bias in the included trials and extracted data. We conducted meta-analyses using random-effects models throughout. We analysed the outcomes at short-term (less than 12 months) and long-term (12 months or more) follow-up. Dichotomous outcomes are reported as a risk ratio (RR) and continuous outcomes are reported as a 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), cell dose, cell type and timing of administration, as well as the use of heparin in the final cell solution.
Fifty-three RCTs that recruited 4159 participants (2297 cell therapy, 1862 controls) were eligible for inclusion.
Cell treatment was not associated with any change in the risk of all-cause mortality at short-term follow-up (24/1145 versus 18/779; RR 0.79, 95% confidence interval (CI) 0.44 to 1.40; 21 studies, 1924 participants; high-certainty evidence) or long-term follow-up (49/998 versus 51/912; RR 0.88, 95% CI 0.60 to 1.31; 22 studies, 1910 participants; high-certainty evidence).
Cell treatment was not associated with any change in the risk of cardiovascular mortality at short-term follow-up (8/348 versus 9/329; RR 0.73, 95% CI 0.31 to 1.71; 9 studies, 677 participants; moderate-certainty evidence) or long-term follow-up (29/641 versus 29/602; RR 0.91, 95% CI 0.55 to 1.53; 14 studies, 1243 participants; high-certainty evidence).
Cell treatment was not associated with any change in the risk of the composite measure of mortality, reinfarction and re-hospitalisation for heart failure at short-term follow-up (5/198 versus 12/181; RR 0.36, 95% CI 0.12 to 1.14; 3 studies, 379 participants; moderate-certainty evidence) or long-term follow-up (24/262 versus 33/235; RR 0.63, 95% CI 0.36 to 1.10; 6 studies, 497 participants; moderate-certainty evidence).
Serious periprocedural adverse events, which were reported as an outcome in 33 trials, were rare (in total, 138 events were reported; high-certainty evidence) and were generally unlikely to be related to cell therapy.
Additionally, no effect on morbidity or quality of life/performance after cell therapy was detected.
In the combined analysis, LVEF, as measured by magnetic resonance imaging, demonstrated an improvement at long-term follow-up (+1.85%, 95% CI 0.13 to 3.56; P = 0.04; 12 studies, 968 participants). In subgroup analyses, baseline LVEF < 45% on MRI was a predictor for LVEF improvement on MRI, but not for overall mortality. There remains an improvement in LVEF as measured by echocardiography and SPECT at both the short- and long-term time points.
Results were robust to the risk of selection, performance and attrition bias from individual studies.