ORLANDO, FL—Delivery of autologous bone marrow mononuclear cells 2 to 3 weeks after primary percutaneous coronary intervention (PCI) does not improve global or regional left ventricular (LV) function at 6 months, according to results of the randomized, placebo-controlled LateTIME trial presented November 14, 2011, at the American Heart Association Scientific Sessions.

The data, presented by Jay H. Traverse, MD, of the Minneapolis Heart Institute at Abbott Northwestern Hospital (Minneapolis, MN), were published online simultaneously ahead of print in the Journal of the American Medical Association.

Most previous cell therapy trials administered bone marrow stem cells 7 days or earlier following AMI, Dr. Traverse noted. But the optimal timing for cell delivery post-AMI is unknown. Moreover, many AMI patients are initially too sick for cell therapy or present to hospitals without stem cell infusion capabilities, making the efficacy of later cell delivery an important issue.

For the trial, investigators randomized 87 patients with significant LV dysfunction (LVEF ≤ 45%) following successful PCI in a 2:1 ratio to intracoronary infusion of autologous bone marrow stem cells (median 150 x 10⁶ cells; n = 58) or a cell-free placebo (n = 29) within 12 hours of bone marrow aspiration. Stem cells were harvested and processed a median of 17.4 days after intervention in the treatment group and 16.8 days in the placebo group.

Primary Endpoints Not Met

Among the 55 stem cell patients and 26 placebo patients who had paired MRI data at baseline and 6 months, no differences were seen between the groups for the primary endpoints of changes in global or regional LV function. In addition, despite small but nonsignificant increases in end diastolic and systolic volumes in the stem cell group, neither endpoint was different from the placebo group. Infarct volume decreased to a similar degree in both groups (table 1).

Table 1. Changes in Global and Regional LV Function from Baseline to 6 Months

Contrary to some previous studies, no significant improvement was observed in patients with the most depressed LVEF at baseline. Likewise, global and regional LV function were similar when patients were stratified by ischemic time or age older than 65 years.

Despite the high-risk cohort, safety events were few and lower in the stem cell arm compared with the placebo arm (5% vs. 17%), with 1 reinfarction, 1 repeat revascularization, and 1 case of heart failure among bone marrow stem cell patients.

Dr. Traverse concluded that while the stem cell procedure is safe, it demonstrated no improvement in LV function at 6 months.

Evidence Tipping Against Cell Therapy?

Discussant Thomas Eschenhagen, MD, of University Medical Center Hamburg-Eppendorf (Hamburg, Germany), reviewed 10 prior randomized bone marrow stem cell trials evaluating changes in LVEF by cardiac MRI after 4 to 6 months. He noted a pattern of positive findings in the earlier trials and negative findings in later ones, but an overall mean weighted difference favoring stem cells (+0.9%; range -0.7 to +2.4). “[However], if one adds the LateTIME results, the benefit approaches zero,” he observed.

The late timing of the stem cell infusion and low patient numbers may help explain the lack of efficacy of cell therapy in LateTIME, Dr. Eschenhagen said. On the other hand, “LateTIME adds to a number of recent [bone marrow stem cell] trials with neutral outcome, arguing against the therapeutic efficacy of stem cell therapy in acute or subacute MI,” he concluded.

Study Details

There were no differences in the baseline characteristics of the treatment groups except for a higher heart rate in the placebo group on initial presentation. Mean age was 57 years; 83% were men. The infarct artery was the LAD in about 92% of patients. In-hospital LVEF following PCI was 36.4% in the stem cell group and 35.0% in the placebo group.

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