Among the 20 or so Cochrane reviews of treatments for myocardial infarction is one that reached its third update in August 2024. It looks at the effects of stem cells, and we asked new lead author, Peter-Paul Zwetsloot from University Medical Centre Utrecht in the Netherlands to tell us about the importance of the review and the latest findings.
Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Among the 20 or so Cochrane reviews of treatments for myocardial infarction is one that reached its third update in August 2024. It looks at the effects of stem cells, and we asked new lead author, Peter-Paul Zwetsloot from University Medical Centre Utrecht in the Netherlands to tell us about the importance of the review and the latest findings.
Peter-Paul: Acute myocardial infarction and subsequent heart disease is an important healthcare problem. Percutaneous interventions and other new medical therapies have led to improved survival, but patients still often have reduced cardiac function, subsequent heart failure and decreased life expectancy. Alongside this, though, the increased survival rates after myocardial infarction, mean that this patient population is growing.
Cell therapy is a therapy with the potential to partially restore cardiac function and provide additional benefits and our review investigates the use of autologous bone marrow mononuclear cells. These are bone marrow cells harvested from the patient themself, which are then transferred to their heart.
The last version of this review was published in 2015 and, for the first time in this update, we are able to provide high certainty evidence. This shows that although the therapy seems safe, there is no evidence to support its use in the current clinical setting of acute myocardial infarction.
For this update, we have added data from 12 randomized trials, including two large Phase III studies. This gives us a final analysis of 53 trials and more than 4100 participants over a period of 20 years of research.
Overall, this provides high quality evidence that autologous bone marrow cell therapy for acute myocardial infarction is safe, but has no beneficial effects on short or long term all-cause mortality or on short or long term cardiovascular mortality. There is moderate quality evidence that autologous bone marrow cell therapy does not influence the composite endpoint of death, reinfarction and rehospitalization; and there were no important differences between different subgroups of patients for these major outcomes.
There remains moderate evidence for a small but significant improvement in left ventricular ejection fraction and this update now shows that this was not only the case for echocardiographic and SPECT measurements, but also for the long-term results when using MRI.
In summary, our review shows that autologous bone marrow cell therapy adds no additional benefit for the current treatment of patients who have had a myocardial infarction. Looking at results and mortality rates over time, the populations in these myocardial infarction trials has likely changed, with improved and timely primary interventions and more supportive medical therapy thereafter leading to better care and reduced mortality and morbidity. In line with this, the effect of bone marrow cell therapy seems to have declined over the last 20 years, with two large well-conducted phase III trials failing to show an undisputable effect of this therapy when it is added to current treatments.
Although the therapy seems safe, these data support advice to not use it for the acute myocardial infarction population as a whole, nor in any subpopulation. Due to the quality of the evidence that has already accumulated and the large number of patients included in the studies, we do not expect there to be any further large scale studies of autologous cell therapy in acute myocardial infarction and feel that the conclusions of this review will remain relevant for the foreseeable future.
Mike: If you would like to read those conclusions and look in more detail at the evidence base, the review is available online. If you go to CochraneLibrary.com and search ‘stem cells for myocardial infarction’, you’ll see a link to it.