Whether administered early or late after an acute ST-segment elevation myocardial infarction (STEMI), an intracoronary infusion of mononuclear cells derived from bone marrow did not improve left ventricular function, the randomized SWISS-AMI trial showed, an article by Todd Neale, MedPage Today Senior Staff Writer, explained.
Four months after the infusion, global left ventricular ejection fraction (LVEF) had not changed significantly either in the patients treated 5 to 7 days after the MI or those treated 3 to 4 weeks after the MI, according to Roberto Corti, MD, of University Hospital Zurich, and colleagues.
And neither group had a significant advantage over a control group that received best medical therapy alone, the researchers reported recently. The findings were first reported at the American Heart Association meeting last year.
"The results of the SWISS-AMI trial may further cool down the euphoria, which initially accompanied the clinical application of progenitor cell-based research," the authors wrote.
"The question whether the measurement of left ventricular ejection fraction is the proper endpoint to assess the clinical utility of cell-based therapy remains open and will await the results of upcoming large outcome trials," they wrote.
Some studies -- but not all -- have suggested that infusing bone marrow-derived mononuclear cells can improve left ventricular function following an acute MI, but a direct comparison of early versus late administration had not been performed.
The SWISS-AMI trial was performed at four Swiss centers and was designed to answer that question, with 200 patients who had a STEMI successfully reperfused within 24 hours of symptom onset and an ejection fraction of less than 45%.
The patients were randomized in equal proportions to receive best medical management alone, an early infusion of bone marrow-derived mononuclear cells, or a late infusion. Both of the treatment groups received best medical therapy.
Cardiac MRI was performed a median of 6 days after the STEMI and at 4 months.
The primary endpoint was the change after 4 months in global LVEF, which was a median of 37% at baseline. The absolute change in the measure was -0.4% in the control group, 1.8% in the early-infusion group, and 0.8% in the late-infusion group; none of the changes were statistically significant.
There were no between-group differences on nearly all of the secondary endpoints, although there was less negative remodeling -- assessed using the left ventricular end-diastolic volume -- in the late-infusion group than in the control group (P=0.04).
The authors reported that "there was no significant difference in the frequency of isolated serious adverse events at 4 months between the three groups, neither of the prespecified, combined clinical endpoint of death, recurrence of MI, repeated coronary revascularization, nor of rehospitalization for heart failure."
Overall mortality at 4 months was 2% even though high-risk patients with large acute MIs were enrolled. No deaths have been reported in the control group.
In an accompanying editorial, Jalees Rehman, MD, of the University of Illinois at Chicago, pointed out some important limitations to the trial, including the use of a surrogate measure (ejection fraction) as the primary endpoint, the short duration of follow-up, and the fact that most of the patients had mild New York Heart Association class I symptoms at follow-up.
But "despite these limitations, the SWISS-AMI trial once again casts doubt on the idea that bone marrow mononuclear cell infusions are beneficial for MI patients," he wrote.
Although a large-scale trial is planned to definitively assess the effects of such infusions on mortality after an MI, "one needs to ask the question whether conducting such a large-scale ... trial in light of the recent negative results and newer scientific advances in the field of cardiovascular regeneration is even appropriate," Rehman wrote.
He pointed out that early studies using cardiac stem cells or mesenchymal stem cells have yielded promising results.
"Each of these cell types requires a more cumbersome isolation and culture procedure than the convenience of extracting bone marrow mononuclear cells and re-infusing them into coronary arteries, but the use of these newer, defined cell types has a stronger scientific footing than the use of bone marrow mononuclear cells," he wrote.
"For regenerative therapies to succeed, we need to ensure that large-scale cell therapy trials are based on the latest and best scientific data and methodology available," he added.
Illustration: Microsoft clipart.
MedPage Today (04/24/13)
Abstract (Circulation; (04/17/13))
Abstract (Circulation; (04/17/13))