Diagnostics & Imaging Week Associate

Thanks to a new landmark study that has just completed enrollment, physicians may soon have a means to identify, at an earlier stage, patients believed to be at risk for heart attack, through evaluation of what is now believed to be a key contributor to the problem, vulnerable plaque.

Abbott Laboratories (Abbott Park, Illinois) reported completion of enrollment in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study designed to increase clinical understanding of vulnerable plaque — a lipid-rich coronary plaque that suddenly ruptures — believed to be a key culprit in producing myocardial infarction.

The cause of most heart attacks was once believed to be the gradual closing of arteries over time as plaque build-up slowly increased, restricting blood and oxygen flow to the heart. However, the vast majority of heart attacks are now believed to be triggered by the rupture of a lipid-rich vulnerable plaque hidden under a thin fibrous cap on the artery wall, causing blood to clot on the plaque and suddenly blocking the artery, according to a statement from Abbott.

For this reason, heart attacks often occur in apparently healthy people who were unaware they have this type of plaque buildup in the walls of their arteries. It has been found that treadmill stress tests, given to help determine whether blood supply is reduced in the arteries that supply the heart, do not indicate whether vulnerable plaque is present. Additionally, vulnerable plaques are not readily evident in angiograms, either, as the hidden plaque may not yet block the vessel.

The PROSPECT study enrolled 700 acute coronary syndrome patients receiving stents in the U.S. and Europe. Patients will be followed up for at least two years and up to five years.

The study will use novel intravascular imaging technology, including a virtual histology system developed by Volcano Therapeutics (Rancho Cordova, California), to correlate plaque characteristics, patient risk factors and biomarker measurements with subsequent heart attacks and other cardiac events, potentially paving the way for physicians to identify and treat at-risk patients before a heart attack occurs.

The study is being sponsored by Abbott and implemented via the company's Abbott Vascular (Redwood City, California) division. The vulnerable plaque program was acquired through Abbott's $6.4 billion acquisition of the Vascular Intervention and Endovascular Solutions businesses of Guidant (Indianapolis) in April.

"As the first prospective natural history study examining whether novel blood and imaging tests are able to identify patients at risk for future death and heart attack, PROSPECT promises to provide groundbreaking data critical to understanding the progression of coronary artery disease, and represents the first step toward identifying patients at high risk who may benefit from preventative therapies," said Gregg Stone, MD, professor of medicine at Columbia University Medical Center and principal investigator of the PROSPECT study during a conference call sponsored by the company to discuss the completion of the trial enrollment.

"We need then to figure out strategies to captivate the vulnerable plaque, reduce the likelihood of the vulnerable plaque either developing further or rupturing," said Stone. "The PROSPECT trial is really the first step to trying to identify patients and lesions which are vulnerable and are likely to cause sudden death, heart attacks and threaten heart attacks. This is really a brave new world and new territory which has never been explored before," he added.

According to Jeff Ellis, PhD, a research advisor for the company's vulnerable plaque program, the goal of Abbott is "to work with physicians to help them advance from treatment of a patient's symptoms to prevention of future heart attacks."

In a conference call, Ellis used the analogy of the way cancer once was treated in contrast to current therapeutic approach to illustrate how heart attack risk is addressed today versus how far it has to go to become more useful.

He noted that 20 years ago, many people died of cancer because there was no efficient way to detect it at its earliest stages. Now, he said, a variety of diagnostic tests are available to identify cancers at those early stages as well as better ways to treat these patients once diagnosed

"Despite new advances in treatment and new advances in cardiovascular medicine, we still have not yet addressed heart attack prevention successfully," Ellis said, adding: "That's because there still is no prospective method that has been shown to signal the future risk of atherosclerotic plaque or the patient's susceptibility to thrombosis."

"What we're hoping is that we will be able to identify a very enriched type of patient and plaque population that will have a high likelihood when we see those types of plaques of saying 'gosh, there may be a one in five chance that in a year or two that plaque is going to cause a heart attack, and we need to do something about it.'"

Stone said he will present baseline demographic and imaging data from the first group of patients enrolled in PROSPECT in October at the Eighteenth Annual Scientific Symposium, Transcatheter Cardiovascular Therapeutics (TCT 2006) in Washington.