The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: the BAMI trial

Abstract

Aims Bone marrow-derived mononuclear cell (BM-MNC) therapy may improve myocardial recovery in patients following acute myocardial infarction (AMI), though existing trial results are inconsistent. Methods and results Originally an open-label, multicentre Phase III trial, BAMI was designed to demonstrate the safety and efficacy of intracoronary infusion of BM-MNCs in reducing the time to all-cause mortality in patients with reduced left ventricular ejection fraction (LVEF, ≤45%) after primary angioplasty (PPCI) for ST-elevation AMI. Unexpectedly low recruitment means the trial no longer qualifies as a hypothesis-testing trial, but is instead an observational study with no definitive conclusions possible from statistical analysis. In total, 375 patients were recruited: 185 patients were randomized to the treatment arm (intracoronary infusion of BM-MNCs 2–8 days after PPCI) and 190 patients to the control arm (optimal medical therapy). All-cause mortality at 2 years was 3.26% [6 deaths; 95% confidence interval (CI): 1.48–7.12%] in the BM-MNC group and 3.82% (7 deaths; 95% CI: 1.84–7.84%) in the control group. Five patients (2.7%, 95% CI: 1.0–5.9%) in the BM-MNC group and 15 patients (8.1%, CI : 4.7–12.5%) in the control group were hospitalized for heart failure during 2 years of follow-up. Neither adverse events nor serious adverse events differed between the two groups. There were no patients hospitalized for stroke in the control group and 4 (2.2%) patients hospitalized for stroke in the BM-MNC group. Conclusions Although BAMI is the largest trial of autologous cell-based therapy in the treatment of AMI, unexpectedly low recruitment and event rates preclude any meaningful group comparisons and interpretation of the observed results.

Injectable Hydrogels for Improving Cardiac Cell Therapy—In Vivo Evidence and Translational Challenges

“…So far, cell therapy has been shown to have little effect in patients with acute myocardial infarction (AMI), despite a body of preclinical evidence showing the opposite [ 23 , 24 ]. This has most recently been shown in the Phase III autologous bone marrow cell therapy in acute myocardial infarction trial (BAMI) [ 25 ]. The investigators concluded that the improvement in the standard of care for AMI patients is simply so good that it requires too many patients, close to 10,000, to demonstrate a potential effect of cell therapy on hard end-points such as death.…”

“…The investigators concluded that the improvement in the standard of care for AMI patients is simply so good that it requires too many patients, close to 10,000, to demonstrate a potential effect of cell therapy on hard end-points such as death. As an important note, this trial did not meet the number of recruited patients and ended up including 375 out of the planned 3000 [ 25 ]. Since this is caused by the control group, the results will most likely be the same across all cell therapies for AMI.…”

Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

“…Large-scale, randomized, placebo-controlled trials show only minor benefits, as confirmed by a meta-analysis published in 2015 [ 61 , 62 ]. In addition, the phase III BAMI trial announced in 2020, suffered slow enrollment and failed to demonstrate mortality benefit with BMMNCs [ 63 ].…”

Highlights from the European society of cardiology congress 2020

“…BAMI trial compared intracoronary infusion of bone marrow-derived mononuclear cells with standard therapy in patients with acute ST elevation myocardial infarction (STEMI) who underwent successful reperfusion therapy [ 11 ]. This randomized, open-label trial enrolled 375 eligible patients and did not show any statistically significant difference in all-cause mortality at 2 years (primary outcomes) and cardiovascular death or hospitalization due to heart failure (secondary endpoint) between the study groups [ 12 ].…”