Meta-analysis: Cell Therapy Improves LV Function in Majority of STEMI Patients

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Intracoronary bone marrow stem cell therapy leads to improved left ventricular (LV) function in most patients with ST-segment elevation myocardial infarction (STEMI), particularly younger patients (under age 55) and those with baseline left ventricular ejection fraction (LVEF) under 40%, according to a meta-analysis published online September 11, 2013, ahead of print in the European Heart Journal.

Researchers led by Ronak Delewi, MD, of the University of Amsterdam (Amsterdam, The Netherlands), looked at 16 trials including 1,641 STEMI patients who were randomized to primary PCI with (n = 984) or without (n = 657) intracoronary stem cell therapy. In 1 trial, patients were treated with thrombolysis first and later with PCI and cell infusion.

The overall treatment effect favored stem cell therapy for LVEF as well as LV end diastolic volume index (LVEDVI) and LV end systolic volume index (LVESVI; table 1).

Table 1. Treatment Effect of Intracoronary Stem Cells on LV Function

P < 0.001 for all.

With regard to LVEF improvement, younger patients (age < 55 years) showed more benefit from intracoronary stem cell therapy (3.38%; 95% CI 2.36-4.39) than older patients (1.77%; 95% CI 0.80-2.74; P = 0.03).

There was also a more pronounced decrease in LVEDVI in younger patients receiving stem cell therapy (-5.70 mL/m²; 95% CI -9.18 to -2.21) compared with older patients (-1.13 mL/m²; 95% CI -4.58 to 2.32; P = 0.001). The same was true for decrease in LVESVI in younger (-4.47 mL/m²; 95% CI -7.32 to -1.62) vs. older patients receiving bone marrow stem cell therapy (-0.82 mL/m²; 95% CI -3.31 to 1.67; P = 0.002).

This pattern was repeated for stem cell therapy in patients with baseline LVEF less than 40%, though the effect for LVEDVI did not reach significance (table 2).

Table 2. Treatment Effect in Patients with Baseline LVEF < 40% vs. ≥ 40%

There was no difference in LVEF improvement by time from primary PCI to cell infusion (< 7 days vs. ≥ 7 days). There was also no difference in LVEF improvement comparing patients with number of injected mononuclear bone marrow cells of < 10⁸ vs. ≥ 10⁸. In addition, no association was found between the presence of microvascular obstruction or infarct size and the effects of bone marrow stem cell infusion. Studies using MRI as LV function assessment did have a smaller treatment effect on LVEF when compared with non-MRI studies (0.16%; 95% CI -0.88 to 1.20 vs. 4.67%; 95% CI 3.69-5.66; P < 0.001).

“In this collaborative meta-analysis, we found that autologous [bone marrow stem cell] infusion is associated with a moderate but statistically significant improvement of LV systolic function and remodeling in patients after STEMI,” the researchers conclude. “This is reflected by a larger increase in LVEF and a greater decrease in LVESVI and LVEDVI in the treated population. In additional subgroup analyses, younger patients and patients with more depressed LVEF at baseline had the largest benefit from [bone marrow stem cell] infusion.”

They note that ageing seems to have a very strong influence on stem cell function, and that both experimental and clinical studies have shown lower absolute numbers as well as functionality of stem cells with increasing age.

Future Trials Awaited

Regardless, the authors add, trials powered to determine the effects of bone marrow stem cell infusion on clinical endpoints are eagerly awaited. One such trial (BAMI), funded by the European Union, will investigate bone marrow stem cell therapy in 3,000 randomized STEMI patients.

In an e-mail communication with TCTMD, Warren Sherman, MD, of Columbia University Medical Center (New York, NY), noted that some of the subgroup definitions seemed rather arbitrary. “Interestingly, patients > 55 years appeared to benefit from the administration of cells in terms of effects on LVEF, although not on LVEDVI or LVESVI,” Dr. Sherman said. “Patients enrolled in these studies were young and the effect of age on stem cell function is an important one, as the authors point out. We can expect clarification of age-related effects from BAMI, which has placed no upper limit on age to qualify.”

A major strength of the paper, he added, is its collaborative design, including investigators from all the studies included in the meta-analysis. “In doing so,” Dr. Sherman said, “they have strengthened the perception of a positive treatment effect from [bone marrow stem cells] and highlighted the parameters that are key in the design of future trials.”

 

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Source:
Delewi R, Hirsch A, Tijssen JG, et al. Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: A collaborative meta-analysis. Eur Heart J. 2013;Epub ahead of print.

 

 

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