Consistently Inconsistent—Bone Marrow Mononuclear Stem Cell Therapy Following Acute Myocardial Infarction
A Decade Later
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A decade ago, 3 potentially groundbreaking trials were published that ushered in a new era of cardiovascular regenerative medicine.1–3 Using autologous bone marrow mononuclear cells (BMCs) in patients with acute ST-segment–elevation myocardial infarction (STEMI), the trials were notable for their clear signal of safety, but discordant in their findings of benefit. Unfortunately, the 1-year results of the SWISS-AMI trial (Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction)4 reported in this issue of Circulation Research again remind us about the inability of BMC therapy in patients with STEMI to demonstrate consistent benefit. Why are there such disparate results in trials using a similar cell product in a similar patient population?
Article, see p 481
REPAIR-AMI (Reinfusion of Enriched Progenitor cells and Infarct Remodeling in Acute Myocardial Infarction),1 remains the largest (n=204) and landmark trial to demonstrate that BMCs improve left ventricular (LV) function in patients after STEMI. Patients were randomized to intracoronary delivery (using stop-flow technique) of BMC versus placebo 3 to 7 days after successful percutaneous coronary intervention (PCI). At 4 months, BMC-treated patients had a significant improvement in ejection fraction (EF) measured by left ventriculography at 4 months compared with placebo (5.5±7.3% versus 3.0±6.5%; P=0.01). In subgroup analyses, the improvement in LVEF was most significant in patients with a baseline LVEF below the median value of 48.9% and in patients treated ≥4 days post MI. At 1 year, there was a significant reduction in the prespecified combined clinical end point of death, recurrent MI, and any revascularization procedure (5.8% versus 1.9%; P=0.01). This trial generated excitement for the potential of cardiovascular stem cell therapy for AMI (as well as other cardiovascular diseases), but this excitement was tempered by the results of a second study, ASTAMI (Autologous Stem cell Transplantation in …