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Change in percent atheroma volume similar following treatment with rosiglitazone, glipizide in patients with type 2 diabetes, APPROACH data show

Sunday, November 16 2008 | Comments
Evidence Grade 7 What's This?
By Selma Kaszczuk

The effect of the insulin sensitizer rosiglitazone versus that of the insulin secretagogue glipizide on intravascular ultrasound (IVUS) measures of atherosclerosis in native coronary arteries among patients with type 2 diabetes do not appear to significantly differ, according to Dr. Richard Nesto, chairman of cardiovascular medicine at Lahey Clinic in Burlington, MA, who presented findings of the APPROACH trial.

He explained that in the past few years, there has been considerable interest in not only whether glycemic control reduces cardiovascular events, but also whether specific agents directed at glucose lowering can reduce cardiovascular events. Dr. Nesto noted that thiazolidinediones, the class of drugs to which rosiglitazone belongs, have been shown to improve glycemic control, lower blood pressure (BP) to a small degree, have a beneficial effect on certain inflammatory biomarkers, improve lipid profiles, and influence the direction of carotid intima-media thickness in both patients with and without type 2 diabetes.

"It is reasonable that thiazolidinediones may therefore reduce the progression of coronary atherosclerosis compared to other drugs to treat diabetes," Dr. Nesto said.

APPROACH included 672 patients with type 2 diabetes who were taking <=2 oral agents and whose hemoglobin A1C levels were between 6.6% and 8.5%. All had a clinical indication for angiography or percutaneous coronary intervention and had >=1 plaque with narrowing of 10% to 50% in a nonintervened artery. Ejection fractions were >=40%, and none of the participants had undergone coronary artery bypass grafting or had renal or liver disease or uncontrolled BP.

The patients were randomized to either rosiglitazone titrated to 8 mg/day or glipizide titrated to 15 mg/d. To achieve a target A1C <=7%, Dr. Nesto indicated that metformin or insulin could be added after 3 months. BP was lower in the rosiglitazone group (128/75 mm Hg) as compared with the glipizide group (131/76 mm Hg; P<.05), and creatinine was higher in the rosiglitazone group (1.02 mg/dL) as compared with the glipizide group (0.98 mg/dL; P<.05).

The study's primary endpoint was change from baseline to 18 months in percent atheroma volume, which was assessed using IVUS in a 40 mm segment (analyzed longitudinally). The analysis included 462 patients (69% of cohort) who had evaluable IVUS assessments at both time points.

Dr. Nesto said the results showed that change in percent atheroma volume decreased 0.21% in the rosiglitazone group and increased 0.43% in the glipizide group, neither of which were statistically significant relative to their respective baseline values. The absolute difference between the 2 groups was a decrease of 0.64% (95% CI, -1.46% to 0.17%) favoring rosiglitazone, but this result also did not reach statistical significance.

However, normalized total atheroma volume, a secondary endpoint, decreased 3.9 mm3 in the rosiglitazone group, which was a significant reduction from baseline (P<.05). In the glipizide group it increased 1.2 mm3, not a significant increase from baseline, although the treatment difference between the 2 groups (decrease 5.12 mm3; 95% CI, -9.98 to -0.26 mm3) favored rosiglitazone and was statistically significant (P=.04).

There was no significant treatment difference between the 2 groups in change in atheroma volume in the most diseased 10-mm segment (both treatment groups experienced a similar decline). There also were no significant differences in major cardiovascular events. The most pronounced between-group difference in terms of adverse events was the incidence of hypoglycemia, which occurred in 8% of rosiglitazone-treated patients as compared with 28% of those treated with glipizide (P<.0001).

"When one looks at the change in percent atheroma volume across prespecified subgroups in the heterogeneity analysis, there are some interesting findings that are hypothesis-generating," Dr. Nesto said, with the analysis suggesting that rosiglitazone may have a greater anti-atherosclerotic effect in patients with more advanced diabetes. (Abstract Oral Session 5221.)

The study was supported by GlaxoSmithKline Plc.

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