Autologous cell therapy may reduce HF hospitalizations in acute MI
Click Here to Manage Email Alerts
Autologous cell-based therapy in patients with acute MI may decrease HF hospitalization, according to the BAMI trial, which was converted to an observational trial due to low patient recruitment.
“BAMI was the first and largest phase 3 clinical trial of autologous bone marrow mononuclear cell therapy conducted by an academic consortium,” Anthony Mathur, MD, from Barts Heart Centre and lead of the Center for Cardiovascular Medicine and Devices at Queen Mary University of London, said during a presentation at the European Society of Cardiology Congress. “Inadequate recruitment and a 75% reduction in all-cause mortality means that BAMI is underpowered to make any significant conclusions regarding the role of autologous cell therapy in the treatment of acute myocardial infarction.”
In the BAMI trial, researchers analyzed data from 375 patients with acute STEMI who were undergoing revascularization. These patients also had left ventricular ejection fraction less than 45% between 2 and 6 days after reperfusion.
“This was chosen because it identified a much higher-risk group of patients that were likely to have an adverse outcome,” Mathur said during the presentation. “At the time of the trial's conception, that group had an all-cause mortality in the region of 11% to 20%.”
Patients were assigned treatment with bone marrow-derived mononuclear cells (n = 185; mean age, 59 years; 16% women) or optimal medical therapy (n = 190; mean age, 60 years; 23% women). The treatment group received an intracoronary infusion of bone marrow-derived mononuclear cells into the culprit coronary artery that was treated with primary PCI between 2 and 8 days after the procedure.
“These were taken under local anesthetic from the posterior-superior iliac spine 50 mL of bone marrow removed and processed in one of the processing sites, to be returned to the center that conducted the primary angioplasty, where the cells were reinfused in the culprit coronary vessel,” Mathur said during the presentation.
The primary endpoint was time from randomization to all-cause mortality.
“With an 11% event rate at the time, it was estimated that 3,000 patients would be needed to demonstrate a 25% reduction in all-cause mortality,” Mathur said during the presentation.
Follow-up consisted of an onsite visit at 30 days after hospital discharge then telephone calls every 3 months for a minimum of 2 years.
This trial was originally designed as a randomized, open label, multicenter, phase 3 outcome trial, but was changed to an estimation study due to a reduced number of patients with a left ventricular ejection fraction less than 45%, a limitation on the duration of funding and a reduction in mortality in patients with acute MI.
“Unfortunately, what became clear early on in the study is that there was a markedly reduced patient population to recruit from, probably due to the success of primary angioplasty and medical therapy across Europe,” Mathur said during the presentation.
At 2 years, all-cause mortality occurred in 3.26% of patients assigned bone marrow-derived mononuclear cells (95% CI, 1.48-7.12) compared with 3.82% assigned optimal medical therapy (95% CI, 1.84-7.84; estimated HR = 0.85; 95% CI, 0.29-2.53). During follow-up, 2.7% of patients in the cell therapy group (95% CI, 1-5.9) were hospitalized for HF vs. 8.1% of those in the control group (95% CI, 4.7-12.5; estimated HR = 0.33; 95% CI, 0.28-0.88).
No differences were observed between the treatment and control groups regarding adverse events at 6 months (62.8% and 54.9%, respectively; estimated HR = 1.2; 95% CI, 0.92-1.55) or serious adverse events at 5 years (41.5% and 60.9%, respectively; estimated HR = 0.96; 95% CI, 0.68-1.36).
No patients assigned to the control arm were hospitalized for stroke at 2 years compared with 2.2% of those assigned the treatment arm (95% CI, 0.7-5.1). However, a case-by-case assessment by the investigators found that they were linked neither to the cell therapy nor the cell infusion procedure.
“BAMI demonstrates the feasibility of standardizing a cell therapy-based approach to the treatments of cardiovascular disease across Europe, but also highlights the challenges of performing future trials of cell therapy in acute myocardial infarction,” Mathur said during the presentation.
The findings were simultaneously published in the European Heart Journal.
Reference:
Collapse
Mathur A, et al. Late-Breaking Science in Acute Coronary Syndromes 1. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).
Click Here to Manage Email Alerts