It’s MAGIC: Cell Therapy Reduces Long-term MACE in MI Patients

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Cell therapy with peripheral blood stem cells mobilized by granulocyte colony stimulating factor (GCSF) reduces long-term adverse clinical outcomes in patients with myocardial infarction (MI) who have been treated with drug-eluting stents (DES). Five-year results of the randomized MAGIC Cell-3-DES trial were published online August 17, 2012, ahead of print in the European Heart Journal.

For the original MAGIC Cell-3-DES trial, Hyo-Soo Kim, MD, PhD, of Seoul National University Hospital (Seoul, South Korea), and colleagues randomized patients treated with DES for acute or nonacute MI (randomized within or after 14 days of onset) to cell infusion (n = 79) or a control group (n = 84). In the cell infusion group, stem cells were mobilized with daily subcutaneous injections of GCSF at 10 µg/kg for 3 consecutive days. Peripheral blood stem cells were then collected and selectively infused into the infarcted myocardium via an over-the-wire balloon catheter at doses of 1 to 2 x 10⁹ mononuclear cells per patient to achieve the minimum target cell dose of 7 x 10⁶ CD34+ cells.

The new results incorporate patients whose short-term findings were previously reported (n = 102) and an additional 61 patients from an extension phase of MAGIC Cell-3-DES.

Baseline characteristics were similar between the cell infusion and control groups. At 6 months, the cell infusion group showed improvement in LVEF compared with baseline (50.6% to 53.4%; P = 0.044); these results were maintained at 2 years (50.6% to 54.1%; P = 0.045). The control group showed no gain in ventricular function from baseline at either time point. However, in looking at absolute change in LVEF, there was no difference between the 2 groups at 6 or 24 months (table 1).

Table 1. Change in LVEF vs. Baseline

At 5-year follow-up, the primary endpoint of MACE (cardiac death, MI, TVR, or hospitalization for heart failure or ischemia) was less frequent in the cell infusion group, driven primarily by a reduction in TVR (table 2).

Table 2. Clinical Outcomes at 5-Year Follow-up

The ability of stem cell therapy to reduce the primary endpoint was more evident at 5 years in diabetics (16.7% vs. 58.3%; P = 0.006) than nondiabetics (24.6% vs. 31.7%; P = 0.311) such that there was a significant interaction between stem cell therapy and diabetes for MACE (interaction P = 0.035).

There were no serious adverse reactions related to GCSF administration and no procedure-related serious adverse reactions during cell infusion.

“Although this study was underpowered to evaluate effects of [peripheral blood stem cell] therapy on clinical outcomes, it suggested that [stem cell] therapy has a potential to reduce cardiovascular events over control, which persisted during the 5-year follow-up,” the researchers conclude, noting that this occurred despite the fact that “improvement of LVEF was not so great.”

LVEF Not a Good Surrogate

The investigators say that LVEF may simply not be a good surrogate to evaluate the efficacy of stem cell therapy in MI patients, especially those “with preserved LV systolic function.”

Proposed mechanisms for why stem cell therapy may reduce long-term cardiovascular outcomes include protection against LV remodeling, reduction of infarct size (evident at 6-month follow-up), and improved myocardial systolic performance, Dr. Kim and colleagues note. Other potential modes of action include angiogenesis, improved myocardial perfusion, and vascular protective effects.

In a telephone interview with TCTMD, Warren Sherman, MD, of Columbia University Medical Center (New York, NY), called the results “very encouraging,” and said that “from the standpoint of safety, it’s not an issue, and from the standpoint of efficacy [of GCSF] in combination with intracoronary infusion, I think it’s a viable strategy.”

He agreed with Dr. Kim and colleagues that LVEF should not be viewed as a surrogate for clinical outcomes. “[It’s] not as predictive as one might have expected based on earlier thinking in this population,” Dr. Sherman said. “So it’s not surprising that small changes or even no change would have [little] impact on clinical events.”

‘Guilt by Association’

In fact, the current trial “substantiates not looking at ejection fraction as a primary endpoint at all,” Dr. Sherman added.

He pointed out that the approach used in the study actually represents a dual therapy, GCSF plus intracoronary infusion, and suggested that previous negative trials of GCSF alone may have caused researchers to shy away from studying the combination.

“It’s almost guilt by association, but it really is not fair because there may be advantages to the dual therapy. GCSF mobilization up front may have some benefits in combination with the more typical approach that people are using for intracoronary administration in this population of patients,” Dr. Sherman said. “On the basis of these results, [this approach] might make a resurgence. Most have given up on GCSF alone, but I think the combination may be worthy of a more careful look.”

 

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Source:
Kang H-J, Kim M-K, Lee H-Y, et al. Five-year results of intracoronary infusion of the mobilized peripheral blood stem cells by granulocyte colony-stimulating factor in patients with myocardial infarction. Eur Heart J. 2012;Epub ahead of print.

 

 

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