Pioglitazone Prevents Progression of Coronary Atherosclerosis in Diabetic Patients With Coronary Artery Disease: Results of the PERISCOPE Trial

March 31, 2008 By Alexandra M. Palmer [mailto:apalmer@perfuse.org]

ACC 08-Chicago, IL: Results of the PERISCOPE trial reveal that pioglitazone slows progression of plaque in type 2 diabetic patients with coronary artery disease in comparison to glimepiride. The results were presented by Dr. Steven E. Nissen at today’s American College of Cardiology Annual Scientific Sessions in Chicago.

The goal of the Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation (PERISCOPE) trial was to compare the effects of two oral glucose-lowering agents (Pioglitazone and Glimepiride) on the rate of plaque formation in diabetic patients with coronary artery disease. The primary endpoint was the change in percent atheroma volume as measured by intravascular ultrasound (IVUS).

The PERISCOPE trial was a prospective, randomized, double-blind, multicenter trial with 543 patients enrolled at 97 hospitals in North and South America. Patients presenting with type 2 diabetes and coronary artery disease for 18 months were randomized to 1-4 mg glimepiride or 15-45 mg pioglitazone after having undergone IVUS to obtain a baseline measurement of atheroma volume. Patients were receiving the maximally tolerated dose by 16 weeks. IVUS follow-up was at 18 months and was performed in 360 patients.

Results of the trial favor pioglitazone over glimepiride in the primary endpoint. Whereas patients treated with glimepiride demonstrated a 0.73% increase in percent atheroma volume (n=181, p<0.001), pioglitazone administration was associated with no significant change in the endpoint (n=179, p=0.44), p=0.002 between groups.

Pre-specified IVUS secondary endpoints included the mean maximum atheroma thickness, total atheroma volume, and atheroma volume in the most-diseased 10 mm sub-segment. Pioglitazone treatment demonstrated a lower mean maximum atheroma thickness (-0.011 mm vs. 0.011 mm, p = 0.006). There was no significant difference in the latter two endpoints between the two drugs.

Other endpoints consisted of changes in the following biological parameters. Pioglitazone was associated with a 0.9 mm Hg decrease in diastolic blood pressure (n=360, p=0.003), while systolic and diastolic blood pressure increased by 2.3 mm Hg and 0.9 mm Hg, respectively, in the glimepiride arm. HDL-cholesterol level increase was greater in the pioglitazone group than in the glimepiride one (16.0% vs. 4.1%, p<0.001). LDL-cholesterol levels rose a bit more with glimepiride use (6.9% vs. 6.6%), but the difference was not statistically significant (p=0.69). In addition, triglyceride levels were reduced by 15.3% with pioglitazone and increased by 0.6% with glimepiride (p<0.001).

Major adverse cardiovascular events occurred in both groups. A greater percentage of glimepiride-receiving patients (n=273) suffered a non-fatal myocardial infarction (1.5% vs. 0.7%), nonfatal stroke (0.4% vs. 0%), non-cardiovascular death (0.4% vs. 0%), coronary revascularization (11.0% vs. 10.7%) and hospitalization for CHF (1.8% vs. 1.5%) than did those under pioglitazone (n=270). Cardiovascular death and hospitalization for unstable angina were more prevalent among patients being administered pioglitazone (1.1% vs. 0.4% and 1.5% vs. 0.7%). However, none of the differences were statistically significant.

These findings are very important clinically, as the population of diabetic patients is increasing.