29 June 2007
Lancet 2007; 369: 2142-2143
MedWire News: Continued research will hopefully lead to stem cell transfer therapies that can improve outcomes for myocardial infarction (MI) patients, conclude experts in a Lancet comment article.
But Harald Arnesen (Ullevål University Hospital, Oslo, Norway) and co-authors challenge the proposal that studies should now be conducted in large populations based on methods used in the recent REPAIR-AMI study.
The researchers reviewed studies published to date of autologous bone marrow cell (BMC) transfer in patients with acute MI. They say results of a 2002 trial and other small uncontrolled trials using the same method "were encouraging," but that three randomized trials were negative for the primary endpoint of improvement in left ventricular ejection fraction (LVEF).
The larger REPAIR-AMI (Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute MI) study included 204 patients with acute MI who received either an intracoronary infusion of BMC or placebo into the infarct artery after successful revascularization by percutaneous coronary intervention.
Patients who received BMC experienced a "modest" improvement in LV function compared with the placebo group at 4 months, at a mean greater increase in LVEF of 2.5%, and a surprisingly significant reduction in events at 12 months, Arnesen and colleagues write.
But the authors say they are concerned at the REPAIR-AMI investigators' conclusion that large-scale trials based on the methods used are now warranted. They believe the benefits in LV function were based on suboptimal measurements of LVEF and volumes, and that the positive clinical effect seems to be driven by the poor outcome in the placebo group.
They suggest that the apparently worse outcomes in the REPAIR-AMI placebo group compared with control groups in other trials could be due to harmful effects of the cell culture medium used for the placebo infusion.
Although the same medium was used for the BMC infusion, they write, "a metabolizing process had been operating during the incubation period which could have attenuated the possible deleterious effects to the injured coronary vessel wall."
The authors conclude: "While results of ongoing adequately powered clinical trials with satisfactory methods for endpoint assessment are awaited, research should also move 'from bed to bench' and focus on unsolved problems, such as the selection of optimum cell type, dosing, timing, and mode of delivery, which will hopefully bring cell therapies close to clinical application."