February 26, 1999

Trial set to probe effects of coronary devices combined with medical therapy

Trial set to probe effects of coronary devices combined with medical therapy

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Dr. David Maron is studying the effectiveness of combining interventional coronary devices with aggressive medical therapy. (Photo by Donna Jones Bailey)

Vanderbilt University Medical Center and the Nashville Veterans Administration Medical Center will be among 39 centers in the United States and Canada to participate in the first-ever clinical trial examining the effectiveness of combining interventional coronary devices with aggressive medical therapy.

Researchers will examine the value of using percutaneous coronary intervention, such as angioplasty and stenting, in combination with an aggressive lifestyle change and medical therapy vs. the strategy of solely using intensive medical therapy in the treatment of coronary heart disease.

The primary endpoint for the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) is all causes of mortality and nonfatal heart attack. The secondary end points include quality of life and economic analysis.

"The study hypothesis is that the addition of percutaneous interventions will be superior to medical therapy and lifestyle change alone," said Dr. David J. Maron, assistant professor of Medicine, medical director of the Dayani Center and director of the Vanderbilt Heart Disease Prevention Program. "We spend a lot of money on procedures in relatively stable patients, but we don¹t really know the value of the procedures for the outcomes we are studying. On the other hand, we know that certain medications and lifestyle changes reduce heart attacks and death.

"This is a landmark trial. The implications are profound."

Whenever there is a narrowing of the arteries, it has been customary to treat the condition with balloon therapies, but there is not enough evidence to show that treatment prevents heart attacks.

The use of aspirin, beta-blockers, statins, and ACE inhibitors can lower the risks of heart attack, Maron said, but the question is whether the same can be said for angioplasty.

"We are in search of the optimal therapy," Maron said. "It is my hypothesis that a tailored approach may turn out to be optimal. Narrowing that causes symptoms that can be treated with an intervention and the underlying disease process can be treated with medications. But we honestly don¹t know all the answers."

The study, which Maron spent the last five years helping design, is expected to see a March launch date. Subjects eligible for cardiac catheterization procedures will be randomly selected and placed in two test groups. One group will receive percutaneous interventions plus medications, while the other will receive medications only.

"We now have drugs that directly influence the biology of the atherosclerotic plaque," said Dr. Douglas E. Vaughan, C. Sidney Burwell Professor of Medicine and chief of the division of Cardiovascular Medicine. "These agents, such as statins, dramatically reduce the incidence of coronary events.

"The COURAGE study, which is aptly named, is designed to compare modern aggressive medical therapy with angioplasty and stenting in preventing future coronary events. This study has important ramifications, and we anxiously await the results," Vaughan said.

Over the next three years, more than 3,200 subjects with moderate to severe heart disease will be studied. Each of the 39 sites will enroll approximately 90 patients who will be followed for an average of four years. The $30 million trial is funded primarily by the Department of Veterans Affairs, with significant additional funding from the Canadian government Medical Research Council and several pharmaceutical companies.

Locally, other investigators involved in the study along with Maron include Dr. David E. Hansen, associate professor of Medicine; Dr. Andres G. Digenio, assistant professor of Medicine; Dr. Raphael Smith, professor of Medicine; and Dr. Dominic L. Raco, assistant professor of Medicine.

Despite a decline in the death rate linked to heart disease, it continues to be the single most important cause of morbidity and mortality in the Western world.