Rosiglitazone Reduces Restenosis Risk in Diabetic Patients
Rosiglitazone helps to prevent restenosis after angioplasty, according to a presentation at the American Diabetes Association 63rd Scientific Sessions.

In a six-month study of 73 diabetic patients in whom 97 stents were implanted, the arteries restenosed in 11.4% of those given rosiglitazone compared with 44.7% of those who received placebo, reported Sung Hee Choi, MD, a fellow in the Division of Endocrinology in the Department of Internal Medicine at Yonsei University College of Medicine in Seoul, Korea.

The findings are "extremely important," given that two thirds of people with diabetes develop cardiovascular disease, most of whom require an intervention that can include stent placement, said Scott Campbell, PhD, national vice president of research and programs at the American Diabetes Association (ADA).

Adding insult to injury, an acceleration of neointimal proliferation in diabetic patients makes them more prone to artery reblockage, said Dr. Campbell, at a press conference at the ADA's annual meeting at which the findings were discussed. The in-stent restenosis rate in diabetic patients is more than 50%, at least twice that of nondiabetic patients, he said.

"As healthcare providers, we better be thinking about what we should do to lower this elevated restenosis rate in diabetic patients, which increases the chance of a second heart attack and/or another intervention and all of its associated risks," he said.

In vitro and animal studies provided a hint that rosiglitazone might do the trick, Dr. Choi said. A peroxisomal proliferator-activated receptor gamma agonist, rosiglitazone inhibits vascular smooth muscle cell growth and migration, the processes implicated in restenosis, she said.

To find out if these anti-inflammatory effects would translate into a clinical benefit in humans, the researchers conducted a prospective trial of 73 patients with type 2 diabetes undergoing stent placement.
The patients, whose average age was 60 years, were randomized to either a loading dose of 8 mg of rosiglitazone before stent placement, followed by 4 mg of rosiglitazone a day for six months, or placebo on the same schedule. Coronary angiography was performed at baseline and at six months. Throughout the trial, the patients continued their standard diabetes therapy with sulfonylureas or biguanides, with doses adjusted to meet standard targets, Dr. Choi said.

At six months' follow-up, four of 35 patients in the rosiglitazone arm had restenosed arteries compared with 17 of 38 patients in the control group, the study showed. When the results were analyzed based on the total number of stents implanted, the results were similar: 10.2% of the 47 stented lesions in the treated patients had blockages of 50% or more compared with 36% of the 50 stented lesions in the control patients (P < .001), Dr. Choi reported. There was also more patent lumen in the treated group, with the six-month median minimal lumen diameter being 1.7 mm in the placebo arm compared with 2.25 mm in the rosiglitazone group, she said.
C-reactive protein levels were significantly lower in the rosiglitazone group than in the placebo arm: 1.4 mg/L vs. 0.6 mg/L (P < .01), the study showed. Since CRP is a well-known marker of inflammation that has been linked to heart disease risk, "the findings suggest that rosiglitazone perhaps modifies, in some shape or form, the inflammatory processes that can lead to restenosis," Dr. Campbell said.

Triglyceride levels were also significantly reduced in the rosiglitazone group: Six-month levels were 96 mg/dL vs. 83 mg/dL in the placebo group, the study showed. Levels of free fatty acids also dropped significantly in the treated patients.
"Treatment with rosiglitazone not only helps to regulate the diabetic patient's glucose levels but at the same time appears to minimize the likelihood of restenosis and associated cardiovascular problems," Dr. Campbell said.

While acknowledging that the findings need to be confirmed in larger, longer trials, Dr. Choi said, "Given the results, I would offer rosiglitazone over, or in conjunction with, other antidiabetic agents as first-line therapy to my patients with diabetes."
Whether rosiglitazone could safely be given to nondiabetic patients undergoing stent placement is an unanswered question, she said. ADA 63rd Scientific Sessions: Abstract 82. Presented June 14, 2003.

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FACT: An experimental vaccine may be able to stop the progression of type 1 diabetes, according to results from a mid-stage clinical trial presented at ADA in New Orleans at the 63rd Annual Scientific Sessions. "The vaccine prolonged what little ability people with advanced diabetes had to make insulin. The study shows that it is possible to inhibit the autoimmune attack on the cells that make insulin, thereby slowing the progression of type 1 diabetes.

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