Diabetes Drug Reduces Development of Heart Stent Blockage

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NEW ORLEANS, June 14 /PRNewswire/ -- Groundbreaking research has shown that rosiglitazone, a drug widely used by diabetes patients to lower blood sugar levels, can also prevent or dramatically reduce the development of new blockages -- restenoses -- in stents placed in atherosclerotic coronary arteries to prop them open after angioplasty, according to a report here today at the American Diabetes Association's 63rd Annual Scientific Sessions.

"Up to one-half of patients receiving stents normally restenose, with the artery blocked again within six months, as did 47% of our control group, but only 12% of those who received daily rosiglitazone restenosed," reported Sunghee Choi, M.D., a Fellow in the Division of Endocrinology, Department of Internal Medicine, at Yonsei University College of Medicine, Seoul, Korea, in a recent interview. "A key marker of inflammation -- hsCRP -- was also reduced, supporting the theory that inflammation plays an important underlying role in cardiovascular disease."

This is the first demonstration that rosiglitazone, a drug with anti- inflammatory action, can prevent in-stent restenosis in humans.

More than 17 million Americans have diabetes, a group of serious diseases characterized by high blood sugar levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease and amputations. Diabetes is the fifth-leading cause of death by disease in the U.S.

Cardiovascular disease is the leading cause of death in people with diabetes. The Yonsei University research was based on the theory that inflammation plays a role in the development of heart disease and that rosiglitazone, one of a class of drugs also known as thiazolidenediones or PPAR-g agonists, could suppress some of that inflammation. The researchers believe that inflammatory proteins (cytokines) and platelet-derived factors influence the migration of smooth muscle cells into the stent, leading to restenosis.

"Aside from its insulin sensitizing benefits, rosiglitazone has been shown to inhibit vascular smooth muscle cell growth and migration in animal models," said Dr. Choi. "The study was conducted to see if this anti-inflammatory benefit would reduce restenosis."

The researchers conducted a double-blind, placebo-controlled, prospective study. A total of 101 diabetes patients, average age 60, in whom angiography had revealed coronary artery blockages, received one or more stents. Then they were randomized to either placebo or 4 mg rosiglitazone for six months, at which time angiography was repeated.

Restenosis was defined as a passageway in the stent that was blocked at least 50% or more. After six months, in-stent restenosis was reduced to only 12% in patients taking rosiglitazone vs. 47% of control patients who did not take the drug. Since some of the patients had more than one stent implanted, the dramatic reduction can also be seen in the total number of restenoses (new lesions) -- 9% in the rosiglitazone group vs. 38% in the control group.

hsCRP -- a highly sensitive C-reactive protein test -- was lower in the rosiglitazone group (1.4+0.3 vs. 0.6+0.2 mg/L, p<0.01). CRP is a well-known marker of inflammation and is under investigation by many groups as a potential indicator of heart disease risk. Triglycerides and free fatty acids also declined in the rosiglitazone group. However, the medication did not reduce all of the known inflammatory markers.

"While we have not proven the mechanism by which the restenoses were reduced, we believe it to be due to the anti-inflammatory action of rosiglitazone in reducing smooth muscle cell migration," said Dr. Choi.

Neither body weight nor blood glucose levels differed in the two groups, with all patients also continuing on conventional diabetes therapy, such as sulfonylureas or biguanides, with doses adjusted to meet standard targets.

The authors concluded that the use of a PPAR-gamma agonist such as rosiglitazone should be strongly considered in people with type 2 diabetes -- not only for glucose lowering and insulin sensitizing but also for its anti- inflammatory effects.

The principal investigator on the study was Bong Su Cha, M.D., professor of endocrinology in that division within the Department of Internal Medicine at Yonsei University College of Medicine.

The American Diabetes Association launched a major educational campaign in 2001 to help physicians Make the Link! between diabetes and cardiovascular disease. The goal is to assure regular monitoring and prompt treatment for such risks as hypertension and high cholesterol levels, in addition to traditional diabetes care to lower blood glucose levels. The Make the Link! Diabetes, Heart Disease and Stroke initiative also includes a component to educate patients about the importance of these issues, as well as lifestyle modifications and medications to lower their risks.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities.

Source: American Diabetes Association
CONTACT: Diane Tuncer, +1-703-299-5510, or Mark Overbay,
+1-703-549-1500, ext. 2290, both of the American Diabetes Association;
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