American College of Cardiology

Clinical trials examine cardiovascular benefits when treating osteoporosis, reducing inflammatory markers, and administering alternative therapy; cost benefits of aggressive treatment also examined
News Conference: 10:15-11 a.m., EST, Wednesday, March 21

(ORLANDO, FLA.)—Three clinical trials being presented at the American College of Cardiology 50th Annual Scientific Session, March 18-21, 2001, address important issues in reducing the risk of heart disease. One study shows that an estrogen-receptor modulator may improve cardiovascular risk factors in postmenopausal women being treated for osteoporosis, another indicates that a lipid-lowering drug can effectively reduce inflammatory markers in patients with cardiovascular risk factors, and the third is a first-time trial of chelation therapy—a form of complementary or alternative medicine—to measure its effectiveness in improving the well-being of heart disease patients. A fourth trial shows that invasive treatment is more effective and no more costly than a conservative approach in treating heart attacks.

Past studies have found that estrogen replacement therapy can reduce blood cholesterol levels but does not prevent—and may even increase—cardiac risk in postmenopausal women. The possible cardiovascular effects of raloxifene, a selective estrogen-receptor modulator, have not been as widely studied.

Now, a large, placebo-controlled study of raloxifene (#423-1), primarily a test of its effect on osteoporosis, has found that the drug also can improve serum cholesterol and other laboratory markers of cardiovascular risk in postmenopausal women. During the three years of follow up in the "Multiple Outcomes of Raloxifene Evaluation" (MORE) trial, raloxifene therapy was associated with neither an increase nor a decrease in the risk of clinical events, such as heart attack or stroke.

Because the potential for increased event risk with estrogen replacement therapy was observed in earlier studies during the first year of treatment, the encouraging three-year MORE results open the door for further research of raloxifene for the prevention of heart disease in postmenopausal women. The findings will be presented by Dr. Elizabeth Barrett-Connor, professor of epidemiology in the Department of Family and Preventive Medicine, University of California, San Diego. (Original presentation on March 21, 8:30 a.m.)

Statin drugs, now widely given to people with elevated blood cholesterol to reduce their risk of heart attacks and stroke, seem to work by reducing arterial inflammation as well as lowering cholesterol. But most of the evidence suggesting that the anti-inflammatory effects of statins play a role in their benefits has been inconclusive.

Now, for the first time, a randomized trial has shown prospectively that treatment with a statin agent, pravastatin, significantly reduces blood levels of C-reactive protein (CRP), an indicator of inflammation, in persons at risk for cardiovascular disease. The findings, according to Dr. Paul M. Ridker, have immense implications for the treatment of millions of Americans who have elevated CRP levels but apparently normal cholesterol levels.

Elevated CRP levels reflect the presence of ongoing inflammation, which is known to play a role in the development of heart disease. Retrospective analyses have strongly suggested that pravastatin, and perhaps other statin drugs, have an anti-inflammatory effect indicated by reductions in CRP levels.

But the placebo-controlled "Pravastatin Inflammation/CRP Evaluation" (PRINCE) trial (#423-5) was intentionally designed to show whether pravastatin can reduce CRP levels. Not only does the drug have that effect, according to the PRINCE findings, but it does so independently of its well-recognized cholesterol-lowering effects, said Dr. Ridker, of Brigham and Women's Hospital, Boston. (Original presentation on March 21, 9 a.m.)

Chelation therapy, which can help rid the body of toxic heavy metals, is widely used in the alternative-medicine community for the treatment of many illnesses. Although some limited data suggest that the chelating agent EDTA may be effective against coronary artery disease, the treatment has never been tested in a randomized, controlled trial until now.

EDTA, or ethylendiamine tetra acetic acid, has been used for more than 60 years for the treatment of heavy metal poisoning, such as by mercury or lead. Suggestions that it may also increase the body's elimination of calcium and other elements involved in atherosclerosis led to its widespread use as an alternative coronary disease treatment, observed Dr. Merrill L. Knudtson, of Foothills Hospital, Calgary, Canada.

Whether EDTA can improve symptoms and other measures of well-being in patients with documented heart disease was the focus of the placebo-controlled "Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health" (PATCH) trial (#423-9). Outcomes in the 80 randomized patients were assessed by exercise stress testing, various measures of vascular function, and a battery of tests designed to gauge changes in quality of life, said Dr. Knudtson. The PATCH trial will be presented by Dr. D. George Wyse, of the University of Calgary. (Original presentation on March 21, 9:30 a.m.)

Last year the TACTICS-TIMI-18 trial found that routine invasive management of patients with acute coronary syndromes, a limited form of heart attack, was more effective at preventing later cardiac events than a more conservative "wait-and-see" approach. Now, an economic analysis from the same trial has found that invasive care can provide those clinical benefits in a cost-effective way.

Whether acute coronary syndromes should be managed invasively—with early cardiac catheterization, including angioplasty as needed-or more conservatively—with catheterization only if symptoms recur or get worse-has long been debated. Investigators from the TACTICS-TIMI-18 study "Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy" (#423-7) previously reported that the risk of later clinical events, including death, was significantly lower with invasive management. The study was among the first of its kind to be performed using such contemporary treatments as coronary stents and platelet glycoprotein IIb/IIIa receptor inhibitors—drugs that discourage blood platelets from clumping to form clots.

The trial's economic analysis, according to Dr. William Weintraub of Emory University, Atlanta, "shows that the benefits of an invasive strategy in acute coronary syndromes can be achieved at essentially no increase in cost." (Original presentation on March 21, 9:15 a.m.)

Studies shed light on harmful link between diabetes and heart disease
News conference: 11:15 a.m.-noon, EST, Wednesday, March 21

(ORLANDO, FLA.)—Diabetes has become an epidemic in the United States, according to a recent report by the Centers for Disease Control and Prevention. Published last month in Diabetes Care, the report describes this chronic condition as a major public health threat that undermines the well-being of more than 16 million Americans and strikes an additional 800,000 people for the first time each year.

Heart disease and other cardiovascular problems are among the many complications linked to diabetes. Studies being presented at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla., March 18-21, 2001, focus on the interaction between diabetes and heart disease and how this harmful relationship influences clinical outcomes.

A study from LDS Hospital in Salt Lake City found that the long-term survival of patients with both heart disease and diabetes may be influenced by the choice of antidiabetic medication (Farangis Lavasani, #1302-163). An analysis of the medical records of more than 1,400 patients showed that patients who were treated with insulin injections only or with sulfonylurea medications, which stimulate the body to secrete insulin, were about two to three times as likely to die during the following two and a half years as were those treated with metformin, a medication that makes the body's cells more sensitive to insulin. (Original presentation on March 21 at a 9-10 a.m. poster session.)

Diabetes doubles the long-term risk of death among patients with a history of heart attack or unstable angina, according to a study from the Duke Clinical Research Institute (Darren K. McGuire, #1283-80). Investigators analyzed data from more than 9,000 patients in the SYMPHONY trial, 17 percent of whom had diabetes. At 90 days, the death rate among diabetic patients was 3.4 percent, as compared to 1.7 percent among those without diabetes. At one year, the rates were 6 percent and 3.5 percent, respectively—still nearly double among diabetic patients. (Original presentation on March 21 at a 10-11 a.m. poster session.)

In general, women don't fare as well as men following angioplasty and stenting—procedures in which a cardiologist inflates a balloon in a narrowed artery in the heart and inserts a metal tube to keep the artery open. Diabetes may somehow equalize the risk, according to a study from the University of Oklahoma, Oklahoma City, and Emory University Rollins School of Public Health, Atlanta (Aaron Kugelmass, #1223-32). Of 723 diabetic patients whose records were analyzed, 44 percent were women. The clinical success rate in this group was 92.6 percent, significantly higher than the 87.5 percent success rate among men, even though the women were older on average. (Original presentation on March 20 at a noon-1 p.m. poster session.)

Elevated blood glucose, even if only to a mild degree in patients who do not have diabetes, can complicate recovery after angioplasty and related procedures, a study from LDS Hospital in Salt Lake City has found (Chloe Allen Maycock, #1091-9). Researchers analyzed the clinical outcomes of more than 2,200 nondiabetic patients with severe coronary artery disease and found that those whose blood glucose exceeded 100 mg/dL were 1.6 times as likely to experience renarrowing of the coronary artery, twice as likely to die, and 1.7 times as likely to have a heart attack within six months. (Original presentation on March 19 at a 9-10 a.m. poster session.)

Moderator: Dr. George Beller, ACC president (2000-01), University of Virginia, Charlottesville