Intracoronary Bone Marrow-derived Progenitor Cells Improved Contractility
Cell infusion should follow revascularization after acute MI in patients with large infarctions.
A number of studies have shown no change in global contractility after bone marrow-derived progenitor cell transplant for acute myocardial infarction (MI), but results published in a recent article in the New England Journal of Medicine have shown increased contractility.
Andreas M. Zeiher, MD, Senior Researcher of the REPAIR-AMI trial, yesterday reconciled these promising data against previous, less optimistic results.
In Zeiher’s preliminary 12-month analysis of REPAIR-AMI, published in the New England Journal of Medicine (2006;355:1210-1221), Zeiher, of the division of cardiology at the University of Frankfurt, Germany, and colleagues showed that there were no myocardial reinfarctions in the group that received bone marrow-derived cells compared with five events in the placebo group (P = .06). Additionally, there were 35 revascularizations in the placebo group compared with 21 revascularizations in the bone marrow-derived progenitor cell group.
Zeiher said that the primary trial endpoint, a combination of all these factors, showed that bone marrow-derived progenitor cell therapy is safe (Figure). The REPAIR-AMI results agree with previous trials in this regard.
Zeiher’s study was a double-blind, placebo-controlled, randomized, multicenter trial of 204 patients with acute MI who were randomly assigned to receive intracoronary infusion of bone marrow-derived progenitor cells or placebo medium. The transplant or infusion into the coronary artery occurred three to seven days after successful reperfusion therapy.
Trial comparisons
The clinical question now is how to select patients for future trials, he said. In a pilot trial, the patients with the lowest ejection fraction at baseline had the most significant improvement.
“Those patients with well-preserved ejection fractions will need an additional treatment because reperfusion has shown no significant benefit,” Zeiher said.
The time to treatment also seemed to make a difference when examining data from recent transplant trials. In some studies, physicians performed transplant within 24 hours of reperfusion therapy. This led to a moderate improvement in global left ventricular function, which did not reach statistical significance.
In the REPAIR-AMI trial, patients were treated at day 5 or 6 after reperfusion therapy and saw a benefit in contractility recovery over time. This could mean two things: “The environment for the transplant itself could be less hostile over time if you let the reperfusion injury heal and let the tissue edema disappear,” Zeiher said. “Or we may harvest different bone marrow progenitor cells at day 4 or 5.”
Zeiher and colleagues determined that based on prior trial data and new results from REPAIR-AMI, intracoronary infusion of bone marrow-derived progenitor cells should follow revascularization after acute MI, but only in patients with large MIs.
“We need to prove these in a large-scale clinical endpoint trial to document the effects on mortality and morbidity,” Zeiher said. “And we need to exercise the utmost care to ascertain functionality of the cells prior to application.”