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Intracoronary delivery of bone marrow mononuclear cells to the infarct zone of patients who have undergone percutaneous coronary intervention following an ST-segment elevation myocardial infarction did not improve left ventricular function at 6 months in the TIME trial.
The trial was designed to examine the difference in effect of infusing the bone marrow mononuclear cells (BMCs) into the infarct-related artery at 7 days after PCI and at 3 days, Dr. Jay H. Traverse said at the American Heart Association meeting.
Unfortunately, neither of these approaches were any better than placebo infusion at improving the recovery of left ventricular function, improving left ventricular volume, or reducing infarct size at 6 months’ follow-up in this double-blind Timing in Myocardial Infarction Evaluation (TIME) clinical trial, reported Dr. Traverse, of the Minneapolis Heart Institute at Abbott Northwestern Hospital.
"However, long-term follow-up of these patients and the development of new composite end points may still reveal a role for this cell type after AMI [acute myocardial infarction]," Dr. Traverse and his associates said in an article published online simultaneously with his presentation (JAMA 2012 Nov. 6 [doi: 10.1001/jama.2012.28726]).
Recent research indicates that the timing of BMC infusion after PCI due to ST-segment elevation myocardial infarction (STEMI) might be critical. In the days following STEMI, there are significant temporal changes in the release of cytokines and growth factors "that may support stem-cell homing and angiogenesis, leading to improved cell survival and engraftment," they noted.
In the TIME trial, a total of 132 high-risk patients were enrolled during a 3-year period after they had experienced STEMI, shown a left ventricular ejection fraction (LVEF) of 45% or less, and were slated for PCI with stenting. These subjects were randomly assigned to have stem cell therapy on either day 3 or day 7 after PCI. After some of these patients were excluded or withdrawn from the study, the remaining 120 patients underwent a second randomization to receive either the autologous BMCs (79 patients) or placebo infusions (41 patients).
The primary end points of TIME were changes in global and regional left ventricular function on MRI scanning at 6 months post PCI. There were no significant differences in these outcomes between subjects who received stem-cell therapy 3 days after PCI and those who received it 7 days after PCI, the investigators reported. There also were no significant differences among the study groups in secondary outcomes such as reduction in infarct volume or change in ventricular volumes.
However, there also were no significant differences in any outcomes between subjects who received active BMCs and those who received placebo infusions.
Dr. Traverse reported no conflicts.
The TIME trial, like two others in the series of studies from the Cardiovascular Cell Therapy Research Network, a consortium funded by the National Institutes of Health, is "well-intentioned, nicely designed, and impeccably executed, but difficult to interpret," said Dr. Eduardo Marban and Dr. Konstantinos Malliaras.
It may be that this treatment is ineffective in this patient population, "in which case the previous positive clinical studies were red herrings." Or it may be that, as Dr. Traverse suggests, the cell product used in TIME was somehow deficient, they said.
Dr. Marban and Dr. Malliaras are at Cedars-Sinai Heart Institute in Los Angeles. Dr. Marban reported being a founder of Capricor, a developer of cardiac stem-cell treatments; both he and Dr. Malliaras reported financial ties to Capricor. These remarks were taken from their editorial accompanying Dr. Traverse’s report (JAMA 2012 Nov. 6 [doi: 10.1001/jama.2012.64751]).
The TIME trial, like two others in the series of studies from the Cardiovascular Cell Therapy Research Network, a consortium funded by the National Institutes of Health, is "well-intentioned, nicely designed, and impeccably executed, but difficult to interpret," said Dr. Eduardo Marban and Dr. Konstantinos Malliaras.
It may be that this treatment is ineffective in this patient population, "in which case the previous positive clinical studies were red herrings." Or it may be that, as Dr. Traverse suggests, the cell product used in TIME was somehow deficient, they said.
Dr. Marban and Dr. Malliaras are at Cedars-Sinai Heart Institute in Los Angeles. Dr. Marban reported being a founder of Capricor, a developer of cardiac stem-cell treatments; both he and Dr. Malliaras reported financial ties to Capricor. These remarks were taken from their editorial accompanying Dr. Traverse’s report (JAMA 2012 Nov. 6 [doi: 10.1001/jama.2012.64751]).
The TIME trial, like two others in the series of studies from the Cardiovascular Cell Therapy Research Network, a consortium funded by the National Institutes of Health, is "well-intentioned, nicely designed, and impeccably executed, but difficult to interpret," said Dr. Eduardo Marban and Dr. Konstantinos Malliaras.
It may be that this treatment is ineffective in this patient population, "in which case the previous positive clinical studies were red herrings." Or it may be that, as Dr. Traverse suggests, the cell product used in TIME was somehow deficient, they said.
Dr. Marban and Dr. Malliaras are at Cedars-Sinai Heart Institute in Los Angeles. Dr. Marban reported being a founder of Capricor, a developer of cardiac stem-cell treatments; both he and Dr. Malliaras reported financial ties to Capricor. These remarks were taken from their editorial accompanying Dr. Traverse’s report (JAMA 2012 Nov. 6 [doi: 10.1001/jama.2012.64751]).
Intracoronary delivery of bone marrow mononuclear cells to the infarct zone of patients who have undergone percutaneous coronary intervention following an ST-segment elevation myocardial infarction did not improve left ventricular function at 6 months in the TIME trial.
The trial was designed to examine the difference in effect of infusing the bone marrow mononuclear cells (BMCs) into the infarct-related artery at 7 days after PCI and at 3 days, Dr. Jay H. Traverse said at the American Heart Association meeting.
Unfortunately, neither of these approaches were any better than placebo infusion at improving the recovery of left ventricular function, improving left ventricular volume, or reducing infarct size at 6 months’ follow-up in this double-blind Timing in Myocardial Infarction Evaluation (TIME) clinical trial, reported Dr. Traverse, of the Minneapolis Heart Institute at Abbott Northwestern Hospital.
"However, long-term follow-up of these patients and the development of new composite end points may still reveal a role for this cell type after AMI [acute myocardial infarction]," Dr. Traverse and his associates said in an article published online simultaneously with his presentation (JAMA 2012 Nov. 6 [doi: 10.1001/jama.2012.28726]).
Recent research indicates that the timing of BMC infusion after PCI due to ST-segment elevation myocardial infarction (STEMI) might be critical. In the days following STEMI, there are significant temporal changes in the release of cytokines and growth factors "that may support stem-cell homing and angiogenesis, leading to improved cell survival and engraftment," they noted.
In the TIME trial, a total of 132 high-risk patients were enrolled during a 3-year period after they had experienced STEMI, shown a left ventricular ejection fraction (LVEF) of 45% or less, and were slated for PCI with stenting. These subjects were randomly assigned to have stem cell therapy on either day 3 or day 7 after PCI. After some of these patients were excluded or withdrawn from the study, the remaining 120 patients underwent a second randomization to receive either the autologous BMCs (79 patients) or placebo infusions (41 patients).
The primary end points of TIME were changes in global and regional left ventricular function on MRI scanning at 6 months post PCI. There were no significant differences in these outcomes between subjects who received stem-cell therapy 3 days after PCI and those who received it 7 days after PCI, the investigators reported. There also were no significant differences among the study groups in secondary outcomes such as reduction in infarct volume or change in ventricular volumes.
However, there also were no significant differences in any outcomes between subjects who received active BMCs and those who received placebo infusions.
Dr. Traverse reported no conflicts.
Intracoronary delivery of bone marrow mononuclear cells to the infarct zone of patients who have undergone percutaneous coronary intervention following an ST-segment elevation myocardial infarction did not improve left ventricular function at 6 months in the TIME trial.
The trial was designed to examine the difference in effect of infusing the bone marrow mononuclear cells (BMCs) into the infarct-related artery at 7 days after PCI and at 3 days, Dr. Jay H. Traverse said at the American Heart Association meeting.
Unfortunately, neither of these approaches were any better than placebo infusion at improving the recovery of left ventricular function, improving left ventricular volume, or reducing infarct size at 6 months’ follow-up in this double-blind Timing in Myocardial Infarction Evaluation (TIME) clinical trial, reported Dr. Traverse, of the Minneapolis Heart Institute at Abbott Northwestern Hospital.
"However, long-term follow-up of these patients and the development of new composite end points may still reveal a role for this cell type after AMI [acute myocardial infarction]," Dr. Traverse and his associates said in an article published online simultaneously with his presentation (JAMA 2012 Nov. 6 [doi: 10.1001/jama.2012.28726]).
Recent research indicates that the timing of BMC infusion after PCI due to ST-segment elevation myocardial infarction (STEMI) might be critical. In the days following STEMI, there are significant temporal changes in the release of cytokines and growth factors "that may support stem-cell homing and angiogenesis, leading to improved cell survival and engraftment," they noted.
In the TIME trial, a total of 132 high-risk patients were enrolled during a 3-year period after they had experienced STEMI, shown a left ventricular ejection fraction (LVEF) of 45% or less, and were slated for PCI with stenting. These subjects were randomly assigned to have stem cell therapy on either day 3 or day 7 after PCI. After some of these patients were excluded or withdrawn from the study, the remaining 120 patients underwent a second randomization to receive either the autologous BMCs (79 patients) or placebo infusions (41 patients).
The primary end points of TIME were changes in global and regional left ventricular function on MRI scanning at 6 months post PCI. There were no significant differences in these outcomes between subjects who received stem-cell therapy 3 days after PCI and those who received it 7 days after PCI, the investigators reported. There also were no significant differences among the study groups in secondary outcomes such as reduction in infarct volume or change in ventricular volumes.
However, there also were no significant differences in any outcomes between subjects who received active BMCs and those who received placebo infusions.
Dr. Traverse reported no conflicts.
Major Finding: The recovery of left ventricular function and volume did not differ between patients who received stem-cell (BMC) therapy in an infarcted artery 3 days after PCI and those who received it 7 days after PCI.
Data Source: This was a randomized, double-blind, placebo-controlled clinical trial involving 120 STEMI patients who underwent PCI with stent placement, received BMC or placebo infusions either 3 or 7 days later, and were followed for 6 months.
Disclosures: This study was funded by the National Heart, Lung, and Blood Institute. Dr. Traverse reported no financial conflicts of interest, but his associates reported numerous ties to industry sources.