Avandia® May Reduce Risk of Cardiovascular Disease

PHILADELPHIA -- The oral anti-diabetes drug Avandia® (rosiglitazone maleate) may decrease the risk of cardiovascular disease, the leading cause of death in the United States, according to data presented here today (June 26, 2001) at the American Diabetes Association's 61st Scientific Sessions.

Results from a study conducted at the University at Buffalo show that Avandia may have a positive effect on blood-vessel abnormalities in people at risk for cardiovascular disease and atherosclerosis, or hardening of the arteries.

Cardiovascular disease affects more than 60 million Americans, with atherosclerosis accounting for 75 percent of deaths from cardiovascular disease. People at risk for these conditions show an inability of the blood vessels to dilate properly (known as vascular reactivity) and increased arterial inflammation, based on mediators for that condition. In the UB study, Avandia was shown to improve vascular reactivity and decrease levels of mediators associated with blood-vessel inflammation.

"Avandia's effect on the prevention of atherosclerosis and its anti-inflammatory properties, as shown in this study, is an extremely important finding that may change the way we look at cardiovascular-disease prevention in the future," said Paresh Dandona, M.D., UB professor of medicine, head of the Division of Endocrinology in the UB School of Medicine and Biomedical Sciences and at Kaleida Health, and lead study investigator. "These data show Avandia has potential beyond the treatment of type 2 diabetes and may prove effective in preventing heart attack or stroke in people without diabetes."

In the UB trial, researchers studied the effects of a six-week course of therapy with Avandia on non-diabetic, obese patients at risk for cardiovascular disease. Avandia is part of a class of drugs called thiazolidinediones (TZDs, or glitazones) that treat insulin resistance, an underlying cause of type 2 diabetes and a key contributor to the development of cardiovascular disease.

Obesity often occurs in conjunction with insulin resistance. People who are insulin resistant cannot effectively use the insulin the body produces and therefore have higher than normal amounts of sugar in the blood. People with insulin resistance may also suffer several different abnormalities that contribute to their increased risk of cardiovascular disease. In addition to obesity, these metabolic abnormalities can include high blood pressure, increased blood clotting, and increased levels of proteins associated with inflammation and atherosclerosis.

The study involved 11 non-diabetic obese patients who were given 4 mg of rosiglitazone daily for a period of six weeks. Fasting blood samples were obtained at 0, 1, 2, 4, 6 and 12 weeks (6 weeks after cessation of the drug). The study measured the effectiveness of Avandia in decreasing the levels of monocyte chemoattractant protein-1 (MCP-1), reactive oxygen species (ROS) and C-reactive protein (CRP), mediators of inflammatory activity associated with the development of atherosclerosis. Study endpoints included the amount of ROS generation, serum CRP and MCP-1 at the start and end of the trial. In addition, researchers measured the effect of Avandia on improving vascular reactivity.

The results showed that there was a significant fall in ROS generation by 40 percent from baseline level. There also was a fall in serum CRP by 30 percent and MCP-1 by 15 percent.

Brachial arterial reactivity (dilation of the artery in the arm) increased 2.5 fold. This change implies that Avandia restores regulation of vessel responsiveness, which is frequently lost in obese insulin resistant patients and patients with type 2 diabetes. Further, this change contributes to the accelerated rates of cardiovascular illness.

"A number of studies have indicated that insulin resistance is an independent risk factor for cardiovascular disease and may actually underlie many of the metabolic risk factors predisposing patients to heart disease," said Dandona. "This research shows that we may be able to prevent the onset of atherosclerosis by targeting insulin resistance directly with Avandia in patients at high risk."

The study was funded by GlaxoSmithKline, manufacturer of Avandia.