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Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction - REPAIR-AMI - Presented at TCT 2006
Description:
The goal of the trial was to evaluate treatment with intracoronary progenitor cell therapy compared with placebo among patients with acute myocardial infarction (MI).
Study Design
Study Design:
Patients Enrolled: 204
Mean Follow Up: 4 months
Mean Patient Age: Mean 56 years
Female: 18
Patient Populations:
Acute ST elevation MI, successful revascularization with either PCI within 24 hours or fibrinolytic within 12 hours followed by PCI, and regional wall motion abnormality
Primary Endpoints:
Absolute improvement in LVEF at 4 months, as assessed by a blinded core lab
Secondary Endpoints:
Primary endpoint in the subgroups of patients with baseline LVEF above and below the median and by time from reperfusion therapy to treatment, change in end-systolic and -diastolic volume, and major adverse cardiac events
Drug/Procedures Used:
Patients were randomized in a double-blind manner to treatment with intracoronary infusion of the infarct-related artery with progenitor cell therapy (progenitor cells derived from bone marrow [BMC] group; n = 101) or matching placebo (n = 103). The progenitor cells were isolated from 50 ml of bone marrow aspirates 3-6 days after MI. Repeat angiography was performed at 4 months.
Principal Findings:
At baseline, 17% of patients were diabetics and 69% had left anterior descending culprit artery as the culprit artery. Primary PCI was the revascularization strategy of choice in 84% of patients. Median time to reperfusion was 4.5 hours. Time from reperfusion therapy to intracoronary infusion was 4 days.
Ejection fraction (EF) at baseline was similar between groups (48% in BMC group and 47% in placebo group). Left ventricular (LV) EF was significantly higher in both groups at 4 months (54% in BMC group and 50% in placebo group); however, the increase in the BMC group was higher than in the placebo group (+5.5% vs. +3.0%, p = 0.01). In subgroup analysis of patients with a baseline EF less than the median (<49%), the improvement in 4-month EF was higher in the BMC group versus placebo (7.5% vs. 2.5%, p < 0.01) with no difference in patients with EF above the median (≥49%) (4.0% vs. 3.7%, p = NS). In the subgroup of patients with treatment initiated ≥5 days from reperfusion therapy, improvement in 4-month EF was higher in the BMC group versus placebo (7.0% vs. 1.9%, p = 0.004) with no difference in patients treated within 4 days (4.5% vs. 3.9%, p = NS).
Change in end-diastolic volume did not differ by treatment group (12 ml for BMC vs. 14 ml for placebo, p = NS), but change in end-systolic volume was lower in the BMC group (-0.6 ml vs. 5.6 ml, p = 0.043). The composite of death, MI, or revascularization at 1 year was lower in the BMC group (n = 23 vs. n = 40, p = 0.01), as was the composite of death, MI, or rehospitalization for heart failure (n = 2 vs. n = 12, p = 0.006).
Interpretation:
Among patients with acute ST elevation MI, treatment with intracoronary progenitor cell therapy was associated with greater improvements in LVEF at 4 months compared with placebo.
Prior small and nonrandomized studies have shown promising results with bone marrow progenitor cell therapy, but the present trial is the first large-scale, randomized, double-blind, and placebo-controlled trial to demonstrate a benefit of progenitor cell therapy in acute MI. Giving these promising mechanistic findings of improved LV function and cardiac remodeling, large-scale trials adequately powered to detect a clinical benefit are warranted. The reduction in reinfarction with BMC therapy is not fully understood, as the mechanism of action was thought to be on LV function, which would presumably have resulted in decreased heart failure, not reinfarction. Conversely, there was no difference between the groups in heart failure.
It should be noted that several of the study authors are shareholders in t2cure, a company attempting to commercially develop regenerative therapy for cardiovascular disease.
References:
Schächinger V, Erbs S, Elsasser A, et al. Intracoronary bone marrow–derived progenitor cells in acute myocardial infarction. N Engl J Med 2006;355:1210-21.
Presented by Dr. Andreas Zeiher at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2006), Washington, DC, October 2006.
Presented by Dr. Volker Schachinger at the American Heart Association Scientific Sessions, Dallas, Texas, November 2005.
Keywords: Coronary Artery Disease, Myocardial Infarction, Bone Marrow, Ventricular Function, Left, Stem Cells, Heart Failure, Diabetes Mellitus
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