American College of Cardiology

New findings will help doctors optimize care in heart attack treatment
News Conference: 8:15-9 a.m., EST, Monday, March 19

(ORLANDO, FLA.)—Delivering the best possible care to heart attack patients relies on research advances in diagnosis and treatment as well as a commitment by health care organizations to assist individual physicians in adopting the latest treatment guidelines. Four studies being presented at the American College of Cardiology (ACC) 50th Annual Scientific Session in Orlando, Fla., March 18-21, 2001, examine both clinical and systematic approaches to optimizing heart attack treatment.

The first study focused on patients with acute coronary syndromes (ACS)-a limited form of heart attack that is one of the most common disorders seen in emergency rooms-and examined the effect of adding to standard medications a drug that helps prevent blood clots. The randomized study showed that clopidogrel, which inhibits platelets, could significantly benefit patients with ACS.

TThe "Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events" (CURE) trial (#405-09) is the largest study of its kind in patients with ACS. Its finding of an added benefit from clopidogrel "is one of the most significant advances for patients with acute coronary syndromes since aspirin," according to the principal investigator, Dr. Salim Yusuf, Hamilton General Hospital and McMaster University, Hamilton, Ontario, Canada.

To break down the blood clots that slow or block blood flow to the heart and cause chest pain, patients with ACS are typically treated with aspirin, which is a weak antiplatelet drug, along with blood thinning medications such as heparin. In the CURE study, patients who received clopidogrel along with these standard medications were significantly less likely to experience serious heart problems over an average of nine months. Clopidogrel's benefit was similar in patients who, in addition to medication, had balloon angioplasty or stenting.

"The widespread use of clopidogrel in addition to aspirin in ACS could prevent about 50,000-100,000 heart attacks, strokes, or deaths every year in North America," Dr. Yusuf said. (Original presentation on March 19, 10:15 a.m.)

Two separate studies examined the use of highly sensitive new blood tests, troponin I and troponin T, for the evaluation of chest pain. Together they provide perspective on how to use the results of these tests to gauge clinical risk. The first, a study from Brigham and Women's Hospital, Boston (Christopher P. Cannon, #820-1), showed that troponin tests alone are not enough to identify all high-risk patients. The OPUS-TIMI 16 trial enrolled more than 2200 patients with ACS. Researchers found that those with a negative troponin test but a high risk score on the basis on clinical characteristics were 2.6 times as likely to experience a heart attack, need bypass surgery or angioplasty, or die during the subsequent 10 months, when compared to those with a low clinical risk score. (Original presentation on March 19, 11:30-11:45 a.m.)

A separate study demonstrated that including troponin results would increase the diagnosis of heart attack by 16 percent. Unlike in other studies, however, researchers from the University of Michigan, Ann Arbor (Mark A. Meier, #1018-89), found that when paired with a negative CK test—the conventional method of diagnosing a heart attack—a positive troponin test identified lower-risk patients who didn't need to be hospitalized as long, experienced fewer complications, and were less likely to die within six months. (Original presentation on March 18 at a 1-2 p.m. poster session.)

The effectiveness of quality improvement programs in increasing physician adherence heart attack treatment guidelines will be the subject of a report by Dr. Kim Eagle (#703-3), of the University of Michigan Medical Center, Ann Arbor. The Guidelines Applied in Practice (GAP) Project was undertaken by the ACC in partnership with the Southeast Michigan Quality Forum Cardiovascular Subgroup and the Michigan Peer Review Organization (MPRO). Its aim was to develop ways to facilitate the use of the ACC/American Heart Association acute myocardial infarction guideline in practice settings. Ten hospitals were selected to participate in the project, beginning last spring. Data on adherence to treatment standards were collected the following fall and showed major improvements following implementation of the GAP Project. Dr. Eagle will discuss the initial findings, based on data from each of the 10 participating GAP hospitals. (Original presentation on March 19 at an 11 a.m.-noon poster session.)

Moderator: Dr. Robert Califf, Duke University Medical Center, Durham, N.C.

Studies probe new approaches to angiogenesis
News Conference: 10:45-11:30 a.m., EST, Monday, March 19

(ORLANDO, FLA.)—When major arteries fail to deliver enough blood to the heart because of narrowed areas or blockages, the body can naturally develop new blood vessels through a process called angiogenesis. A number of studies have tested whether it is possible to stimulate the growth of new blood vessels with proteins, or growth factors, as a potential treatment for ischemia—pain-producing low blood flow to the heart or leg muscles due to vascular disease—but the results have mostly been disappointing. The growth factors can be administered directly into a patient's bloodstream or indirectly using various gene-therapy techniques.

Four studies being presented at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla., March 18-21, 2001, shed new light on the process of angiogenesis and its possible therapeutic uses. One explores whether it is more effective to deliver growth factors through a genetically altered virus, rather than directly. Another suggests that growth factors can improve blood flow to leg muscles. A third suggests that some people may be naturally resistant to angiogenesis. And a fourth shows that ultrasound can track the development of new blood vessels.

The multicenter "Adenovirus FGF Angiogenic Gene Therapy" (AGENT) trial tested the administration of a virus that had been genetically modified to release one of the major growth factors involved in the development of new blood vessels, fibroblast growth factor-4 (FGF-4). In this study (#405-3), 79 patients with heart disease received injections of the genetically altered virus at five different dosage levels. They were evaluated over the next three months to test the treatment's safety and whether it led to improvements in blood flow to the heart—indirectly measured by exercise testing. The AGENT trial is one of the largest of studies of its kind to use a genetically altered virus as a means to deliver angiogenic growth factors. Preliminary findings will be presented Dr. Cindy L. Grines, of William Beaumont Hospital in Royal Oak, Mich. (Original presentation on March 19, 9:30 a.m.)

Direct administration of growth factor proteins, despite disappointing results in the heart, may work well in patients with reduced blood flow to the leg, according to the results of a large randomized trial (#405-5). The "Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for Intermittent Claudication" (TRAFFIC) study is the first large, phase II study to examine direct infusion of growth factors to stimulate angiogenesis in patients with peripheral artery disease, according to Dr. Robert J. Lederman. "And it's the first angiogenesis trial in either peripheral vessel or coronary artery disease to show a benefit," he said.

In the placebo-controlled TRAFFIC trial, patients who experienced pain in their leg muscles due to reduced blood flow, a condition called intermittent claudication, received infusions of a bioengineered angiogenic protein, recombinant fibroblast growth factor-2 or rFGF-2. After 180 days, the treatment was associated with improvements in symptom-free walking time and other measures of increased blood flow in the leg muscles.

Dr. Lederman, of the National Heart, Lung, and Blood Institute, Bethesda, Md., took part in the TRAFFIC study as a co-principal investigator while at the University of Michigan, Ann Arbor. (Original presentation on March 19, 9:45 a.m.)

An inborn resistance to angiogenic growth factors may prevent some people from developing new blood vessels in the heart, according to a small study led by researchers at St. Thomas' Hospital, KCL, London (Pier D. Lambiase, #878-2). The researchers inflated an angioplasty balloon in a coronary artery of 28 patients with a history of stable heart disease, blocking blood flow to a portion of the heart. They found that some patients had already developed a network of extra blood vessels that were able to supply the heart during the blockage, while others had not. Laboratory tests revealed certain blood characteristics in this second group of patients that suggested they were naturally resistant to angiogenesis. (Original presentation on March 21, 8:45-9 a.m.)

An animal study from the University of Pennsylvania School of Medicine, Philadelphia (Emile Mohler, III, #1074-159), evaluated the ability of ultrasound to detect the development of new blood vessels in tissue deprived of adequate blood flow. To do this, researchers surgically removed a major artery in the right hindleg of 10 pigs, then tracked the return of blood flow to the limb over about one and a half months. They found that ultrasound could detect new blood flow within about one week, was able to visualize angiogenesis, and identified areas still deprived of enough blood. (Original presentation on March 18 at a 3-4 p.m. poster session.)

Moderator: Dr. Valentin Fuster, Mount Sinai Medical Center, New York City

Studies shed light on cardiovascular effects, safety of sildenafil (Viagra®)
News Conference: 12:30-1:15 p.m., EST, Monday, March 19

(ORLANDO, FLA.)—Two studies being presented at the ACC 50th Annual Scientific Session in Orlando, Fla., March 18-21, 2001, suggest that one of the ways sildenafil (Viagra®) improves sexual function may be by enhancing the response of the heart and blood vessels to exercise. A third study offers evidence of the drug's safety.

The first study, from St. Vincent's Hospital and the University of New South Wales, Sydney, Australia (Charalambos Vlachopoulos, #1163-185), involved 27 patients who were randomly assigned to receive sildenafil or a placebo drug. Researchers found that sildenafil made the arteries less stiff and reduced blood pressure, which could be expected to help the heart pump the additional blood needed to meet the physical demands of sexual intercourse. (Original presentation on March 19 at a 3-4 p.m. poster session.)

A separate study from Heart Institute of Sao Paulo (Edimar A. Bocchi, #812-5), evaluated 18 patients with erectile dysfunction and moderate congestive heart failure. Study participants walked for six minutes and, later, exercised as vigorously as possible on a treadmill. Those who were randomly assigned to receive sildenafil had a lower blood pressure and heart rate and were able to exercise longer and harder than those who received a placebo. Sildenafil also appeared to reduce the activity of renin, a protein that can be harmful to heart failure patients when produced in excessive amounts. (Original presentation on March 19, 10:15-10:30 a.m.)

A third study suggests that concerns that sildenafil may increase the risk of a heart attack may be unfounded. Investigators from the Drug Safety Research Unit, Southampton, United Kingdom (Saad A. W. Shakir, # 1302-162), tracked the safety of sildenafil use in more than 5,600 patients as part of the ongoing "Sildenafil Prescription-Event Monitoring Study." They found that the rates of heart attack and other related heart problems were no higher among sildenafil users than the general population. (Original presentation on March 21 at a 9-10 a.m. poster session.)

Moderator: Dr. Adolph Hutter, Massachusetts General Hospital, Boston