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Pioglitazone prevents progression of coronary atherosclerosis in patients with CAD, diabetes

Tuesday, April 08 2008 | Comments

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What's This? By Nancy Stanley

Treatment with pioglitazone appears to result in a significantly lower rate of progression of coronary atherosclerosis relative to treatment with glimepiride in patients with coronary artery disease and type 2 diabetes, results of a new study show.

The double-blind PERISCOPE trial included 543 patients with coronary artery disease and type 2 diabetes who were randomized to receive glimepiride 1 mg to 4 mg or pioglitazone 15 mg to 45 mg. The drugs were titrated to the maximum tolerated dose by 16 weeks. In all, 360 participants underwent intravascular ultrasonography at baseline to determine atheroma volume and again after 18 months of treatment.

The patients who received pioglitazone had a nonsignificant reduction of 0.16% in percent atheroma volume. However, the patients who received glimepiride had a significant increase of 0.73% in percent atheroma volume relative to baseline (P<.001). The difference between the groups was also significant (P=.002).

"These data demonstrate that, after 18 months of treatment, patients assigned to glimepiride had unequivocal progression of coronary atherosclerosis, whereas pioglitazone-treated patients had no progression," Dr. Steven Nissen, lead researcher, said.

"To our knowledge, this is the first study in which a diabetes therapy has been shown to slow or prevent progression of coronary atherosclerosis," he added.

Additionally, mean maximum atheroma thickness increased by 0.011 mm in the glimepiride group and decreased by 0.011 mm in the pioglitazone group. The difference between the groups was significant (P=.006). For the secondary endpoints of total atheroma volume and atheroma volume in the most diseased 10 mm subsegment, there were no statistical differences between the treatment groups.

Mean hemoglobin A1C levels decreased from 7.4% at baseline in both treatment groups. The initial reduction in A1C was greater in the glimepiride group; however, the patients who received pioglitazone had a more sustained benefit. Averaged for the duration of the trial, the mean difference in A1C was 0.19% (P=.03), favoring pioglitazone.

Further, the differences in blood pressure favored pioglitazone. Specifically, mean systolic BP increased 2.3 mm Hg in the glimepiride group and increased 0.1 mm Hg in the pioglitazone group, which resulted in a significant between-group difference (P=.03). Mean diastolic BP increased 0.9 mm Hg in the glimepiride group and decreased 0.9 mm Hg in the pioglitazone group. This between-group difference was also significant (P=.003).

LDL cholesterol increased slightly in both groups (6.9% with glimepiride vs 6.6% with pioglitazone), but there were no statistically significant differences between the groups (P=.69). However, HDL cholesterol, C-reactive protein (CRP), and triglyceride levels improved significantly in the pioglitazone group relative to the glimepiride group (P<.001 for all). HDL cholesterol increased 16.0% with pioglitazone compared with 4.1% for glimepiride. The respective decreases in CRP were 44.9% and 18.0%, whereas triglycerides decreased 15.3% with pioglitazone and increased 0.6% with glimepiride.

The composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke occurred in 2.2% of the patients who received glimepiride and in 1.9% of the patients who received pioglitazone. Dr. Nissen noted that the study was small and was not powered to assess major cardiovascular events.

Hypoglycemia and angina were more common with glimepiride treatment. Edema, fractures, and weight gain were more frequent with pioglitazone treatment, as were blood urea nitrogen levels that exceeded 30 mg/dL.

Dr. Nissen noted that there are few trials that examine endpoints other than glycemic control for diabetes drugs.

"Given the recent controversy about the effects of diabetes treatments on cardiovascular disease, we urgently must close this knowledge gap," he added. (Presentation 407-5.)

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