During a heart attack, every minute counts, especially when the type of heart attack is a STEMI (ST segment elevation myocardial infarction). STEMI is the most fatal type of heart attack and is caused by a prolonged blockage of blood supply in the heart, which weakens or deadens the heart muscle.
In a recent clinical trial named PreSERVE AMI, research investigators from 60 different sites conducted one of the largest studies using bone marrow cell therapy for heart attack in the United States. The study treated 161 patients following a STEMI heart attack using their own bone marrow cells in hopes of improving their recovery process.
“For cardiologists, our key goal is to keep patients from progressing to worsening heart muscle function and death after a major heart attack,” said Dr. Arshed A. Quyyumi, professor of medicine at Emory University School of Medicine, co-director of the Emory Clinical Cardiovascular Research Institute and lead principal investigator of the PreSERVE AMI study. Heart attack patients are usually at high risk of downstream adverse events, including chronic heart failure, recurrent heart attack, significant arrhythmias, premature death or acute coronary syndrome.
About the PreSERVE AMI Clinical Trial
The PreSERVE AMI study, sponsored by NeoStem, Inc., produced promising results that will allow stem cell researchers to continue making progress in determining the cell type and dose that benefit patients. After receiving the standard of care following a heart attack, which is stenting, participating patients were enrolled if their ejection fraction, a measure of the heart’s pumping capacity and indicator of the severity of the attack, was less than 48 percent.
After trial enrollment, patients had bone marrow cells extracted, sorted and then re-injected into the heart. Bone marrow contains rare cells which are believed to promote healing and recovery of blood flow. In this study, extracted bone marrow cells were shipped to NeoStem’s facility where sophisticated stem cell technology sorted and selected the rare cells called CD34+ cells before they were returned for re-injection into the patient.
The stem cell study was randomized and not all patients received the same dose of cells — some received the minimum of 10 million cells while others received up to 40 million — and a half of participants received placebo.
Discovery and Results of the PreSERVE AMI Clinical Trial
Recovery and outcomes of PreSERVE AMI were assessed in several ways: MACE (major adverse cardiac events, ranging from hospitalization for chest pain to death), ejection fraction and blood flow in the heart. Cardiac imaging was performed six months after treatment and MACE reported from an average of twelve months of follow-up.
Highlights of initial trial results include:
- A statistically significant mortality benefit in patients treated with CD34+ as compared to the placebo group. Mortality was 3.6 percent in the control group, and zero in the treatment group.
- A statistically significant dose-dependent reduction in serious adverse events.
- MACE occurred in 14% of control participants, in 17% of subjects of who received less than 14 million CD34+ cells, in 10% of subjects who received greater than 14 million CD34+ cells, and in 7% of subjects who received greater than 20 million CD34+ cells. Therefore, it appears that the numerical decrease in MACE is dependent on cell dose size.
- Patients treated with a dose of greater than 20 million CD34+ cells were seen to have a statistically significant improvement in their ejection fraction compared to the placebo group.
- No significant effects on improvement in blood flow, measured by SPECT imaging, between the treatment and the control group based on 6 months of data.**
According to Dr. Quyyumi, the U.S. Food and Drug Administration (FDA) officials have told stem cell researchers using cell therapy that MACE (clinical outcomes) are the important measure of success and SPECT imaging is not, although imaging provides insightful information on the heart and therapy being issued.
Summary of PreSERVE AMI phase II Clinical Trial
In the treatment group that received the largest dose of CD34+ cells, the MACE rate was half that of control group, which is a good indicator that cell dose impacts MACE outcomes. But comparing that measure to the placebo group (versus the entire treatment group), bone marrow cell therapy did not have a significant effect on MACE.
One positive, NeoStem has reported that because of this phase II trial, they are now able to standardize their procedures so that in the future, every patient should be able to receive 20 million CD34+ cells.
“It is encouraging to see clinically meaningful results this early in the study, and I look forward to future data readouts,” says Dr. Quyyumi. He is hopeful that additional follow-up trials should continue to make the effect of cell therapy treatment on clinical outcomes more clear.
“Research and discovery are important components to delivering exceptional patient care,” states Dr. Quyyumi. “Clinical trials are an iterative process that allows us to gain answers to the many questions we have about disease and treatment therapies, regardless of whether the clinical trial produces the outcome we want or expect.”
**Worthy to note, some patients who received cell therapy treatment had delays in getting stents (average 931 vs. 569 minutes), which puts the treated group at a disadvantage in terms of the heart’s recovery. This happened by chance resulting from the randomization of participants to placebo vs. treatment and not because of the treatment process since all bone marrow-related treatment procedures occurred after stenting.
About Emory Heart & Vascular Center
The Emory Heart & Vascular Center is comprised of four major areas of cardiovascular care– cardiology, vascular surgery, cardiothoracic surgery, and cardiac imaging. Each area is committed to providing superior cardiac and vascular patient care, promoting overall heart health, pioneering innovative clinical cardiovascular research, and training the best heart specialists and cardiologists in the world.
About Arshed Quyyumi, MD
Dr. Arshed A. Quyyumi has been involved in clinical translational research in cardiovascular diseases for over 30 years. Dr. Quyyumi received his undergraduate degree in Pharmacology and medical degree from the University of London, England. He completed his residency at Guy’s and Royal Free Hospitals in London, and cardiology fellowships at National Heart Hospital, London; Massachusetts General Hospital, Boston; and the National Institutes of Health. After completion of his residency and fellowship, he served in several capacities in the Cardiology Branch of National Heart Lung and Blood Institute, NIH in Bethesda, MD, including Senior Investigator and Director of the Cardiac Catheterization Laboratory. In 2001 he was appointed Professor of Medicine in the Division of Cardiology at Emory University School of Medicine, and in 2010 he was named Co-Director of the Emory Clinical Cardiovascular Research Institute (ECCRI). Since 2005, Dr. Quyyumi has been awarded more than $9 million in research funding. He serves on the Editorial Boards of several national journals, is a member on several Scientific Advisory Boards, and is a reviewer for the NIH-NHLBI Study Sections. Dr. Quyyumi has authored more than 250 peer-reviewed publications and has been an invited speaker and session chair at numerous National and International scientific meetings and conferences.
Dr. Quyyumi’s research focus includes vascular biology, angiogenesis, progenitor cell biology, mechanisms of myocardial ischemia, the role of genetic and environmental risks on vascular disease, genomics, and metabolomics. Other interests have spanned the fields of personalized medicine and disparities in cardiovascular diseases. During his academic career, Dr. Quyyumi has carried out more than 50 NIH, industry-funded, or investigator-initiated projects, including numerous clinical trials. Dr. Quyyumi is a member of NeoStem’s advisory board. This relationship has been reviewed and approved by Emory University School of Medicine.