TCT: One-Year Data Confirm Benefit of Stem Cell Therapy After MI

WASHINGTON, Oct. 26 -- Infusion of bone marrow-derived progenitor cells directly into a coronary infarct reduced by about half the risk of death, MI, or another revascularization procedure at 12 months, compared with patients getting sham infusions.

That was the latest analysis of data from the REPAIR-AMI (Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute MI) trial, reported by Andreas M. Zeiher, M.D. of Johann Wolfgang Goethe University in Frankfurt, Germany, at the Transcatheter Cardiovascular Therapeutics meeting here.

The four-month results of REPAIR-AMI were published last month in the New England Journal of Medicine. In that paper Dr. Zeiher and colleagues reported a statistically significant 2.5% improvement in global left-ventricular ejection fraction at four months for patients randomized to the bone marrow injection (P=0.01).

After adjusting for age, diabetes, time to infusion, baseline left ventricular ejections fraction, end systolic volume and aldosterone antagonist use at hospital discharge, the odds ratio for a combined endpoint of death, MI, or revascularization was 0.56 among patients who received the progenitor cell infusions (95% confidence interval 0.32-0.95, P=0.033), he said.

Dr. Zeiher said the results confirm the safety of intracoronary infusion of bone-marrow-derived mononuclear cells and the treatment improved functional recovery with a significant reduction of the combined end point of death, acute MI, or rehospitalization, and the predefined endpoint of death, acute MI, or revascularization.

REPAIR-AMI randomized 204 revascularized acute MI patients. Dr. Zeiher cautioned that despite the encouraging results, the trial was not powered to assess hard clinical endpoints. Nonetheless, he said that based on the results the REPAIR-AMI investigators are moving forward with plans for a 1,200-patient trial.

Dr. Zeiher said that the positive results for REPAIR-AMI were due in part to the timing of the infusion at four to six days after reperfusion.

He speculated that tissue edema may be present earlier than day four so that "you have release of toxic products into the reperfused area, and this may be very hostile for the cells that have to home there and stay alive for a couple of days."

In addition, this point post infarction may be the best time to harvest cells, because infarction appears to trigger activation of potentially more potent progenitor cells. Finally, he said that by four days, one can "identify patients in whom reperfusion has failed to produce ventricular functional recovery."

These patients with a poor prognosis have the most to gain from the intracoronary infusion, he said.

Discussant Cindy Grines, M.D., of William Beaumont Hospital in Royal Oak, Mich., pointed out that the clinical outcomes are not explained by the very modest improvement in LVEF-an increase of 5.5% from baseline but only 2.5% better than the average increase in the placebo arm.

Dr. Zeiher agreed and conceded that he and his colleagues have not yet identified the true mechanism behind the observed improvement.

REPAIR-AMI was supported by a grant from Guidant, which also provided the balloon catheters. Eli Lilly supplied ReoPro (abciximab). Dr. Zeiher received consulting fees from Guidant and is a shareholder of t2cure.