Diabetes Medication May Help Slow Plaque Build-up In Coronary Arteries

Atherosclerosis (process in which plaque builds up in the inner lining of the arteries) in patients with diabetes is particularly aggressive, characterized by higher cardiovascular event rates. Cardiovascular disease is the cause of death in approximately 75 percent of patients with diabetes. Determining the optimal treatment for coronary artery disease for patients with diabetes has important public health implications, according to information in the article.

There is little evidence to support a preference of one class of glucose-lowering medication over any other as a means to reduce the severity of atherosclerotic disease. Sulfonylureas, such as glimepiride, have been available for decades and represent one of the most commonly-used classes of antidiabetic therapy. Thiazolidinediones (TZDs; such as pioglitazone) are a relatively new class of antidiabetic agents.

Steven E. Nissen, M.D., of the Cleveland Clinic, and colleagues conducted the PERISCOPE trial to directly compare the effectiveness of two alternative approaches for treating hyperglycemia, an insulin-providing strategy (glimepiride) vs. an insulin-sensitizing strategy (pioglitazone), in reducing progression of atherosclerosis in 543 patients with type 2 diabetes and coronary disease. The randomized, multicenter trial included 97 academic and community hospitals in North and South America (enrollment August 2003 - March 2006).

The patients underwent coronary intravascular ultrasonography to measure progression of atherosclerosis and were randomized to receive glimepiride or pioglitazone for 18 months. Atherosclerosis progression was measured by the change in percent atheroma volume (PAV; a measurement of plaque build-up in an artery) with repeat intravascular ultrasonography examination in 360 patients at study completion.

The primary efficacy measure, change in PAV, increased 0.73 percent in the glimepiride group and decreased 0.16 percent in the pioglitazone group. An alternative analysis imputing values for patients who did not have follow-up ultrasound procedures and based on baseline characteristics showed an increase in PAV of 0.64 percent for glimepiride and a decrease of 0.06 percent for pioglitazone. A secondary efficacy measure, change in maximum atheroma thickness increased in the glimepiride group and decreased in the pioglitazone group.

"The observation of a significant benefit for pioglitazone treatment represents, to our knowledge, the first demonstration of the ability of any hypoglycemic agent to slow the progression of coronary atherosclerosis in patients with diabetes. Evidence for a slowing of disease progression has proven a very challenging end point in recent years with the prominent failure of several promising approaches," the authors write.

"Patients randomized to pioglitazone exhibited a lower rate of progression of coronary atherosclerosis across a wide array of prespecified and exploratory subgroups. These finding may have important implications for defining the optimal strategy for management of patients with type 2 diabetes and coronary atherosclerosis," the researchers conclude.

Journal reference: JAMA. 2008;299[13]:1561-1573.  

Editorial: Does PERISCOPE Provide a New Perspective on Diabetic Treatment?

In an accompanying editorial, Philippe Gabriel Steg, M.D., of the Centre Hospitalier Bichat-Claude Bernard, Paris, and Editor, JAMA-français, and Michel Marre, M.D., Université Paris VII Faculté de Médecine X Bichat, Paris, comment on the findings of Dr. Nissen and colleagues.

"The results of the PERISCOPE trial, even though they relate to a surrogate end point, are consistent with the modest clinical benefit demonstrated for the prevention of coronary events with pioglitazone, within PROACTIVE and other trials. However all glitazones share a common adverse effect on heart failure, and other noncardiovascular adverse effects, such as bone fractures. ... Overall, in the current context of concerns regarding the cardiovascular safety of glucose lowering and regardless of the mechanisms involved, PERISCOPE provides a reassuring perspective for patients with type 2 diabetes and high cardiovascular risk."

Reference for editorial: JAMA. 2008;299[13]:1603-1604.