Effect of Rosiglitazone on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Abstract

the APPROACH Study GroupBackground-Rosiglitazone has several properties that may affect progression of atherosclerosis. The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History (APPROACH) study was undertaken to determine the effect of the thiazolidinedione rosiglitazone on coronary atherosclerosis as assessed by intravascular ultrasound compared with the sulfonylurea glipizide. Methods and Results-This was a randomized, double-blind, controlled 18-month study in 672 patients aged 30 to 80 years with established type 2 diabetes mellitus treated by lifestyle, 1 oral agent, or submaximal doses of 2 oral agents who had at least 1 atherosclerotic plaque with 10% to 50% luminal narrowing in a coronary artery that had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention. The primary outcome was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention. Secondary outcomes included change in normalized total atheroma volume and change in total atheroma volume in the most diseased baseline 10-mm segment. Rosiglitazone did not significantly reduce the primary outcome of percent atheroma volume compared with glipizide (Ϫ0.64%; 95% confidence interval, Ϫ1.46 to 0.17; Pϭ0.12). The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide (Ϫ5.1 mm 3 ; 95% confidence interval, Ϫ10.0 to Ϫ0.3; Pϭ0.04); however, no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment (Ϫ1.7 mm 3 ; 95% confidence interval, Ϫ3.9 to 0.5; Pϭ0.13). Conclusions-Rosiglitazone did not significantly decrease the primary end point of progression of coronary atherosclerosis more than glipizide in patients with type 2 diabetes mellitus and coronary atherosclerosis. Clinical Trial Registration-http://www.clinicaltrials.gov.

Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: Rationale for the active-comparator CAROLINA trial

“…14,15 The other 14 longterm RCTs (Table 1), including A Diabetes Outcome Progression trial (ADOPT, n = 4360), 32,33 also indicate that SUs were not associated with an increase in CVD risk when compared head-to-head trial with thiazolidinediones (glitazones), DPP-4 inhibitors, metformin or glucagon-like peptide-1 (GLP-1) analogues. [26][27][28][32][33][34][35][36][37][38] The same lack of an adverse outcome was observed when SUs were used as part of a treatment strategy to obtain different glycaemic targets, [14][15][16][17][18][19][39][40][41][42] including the ADVANCE (n = 11,140). 17 However, it must be noted that none of the studies targeting 'similar level' of glycaemic control in the treatment arms were powered to demonstrate CV safety/benefits, and there were inconsistencies in how the CVD events were reported and adjudicated.…”

“…23,24 To date, the large CV outcome trials have essentially assessed the impact of multiple combinations of glucose-lowering agents as part of an overall treatment regimen (e.g. UKPDS, ACCORD 28 ]. Thus, a comparative understanding of the CV impact of the most widely used diabetes drugs is for the most part lacking.…”

Rosiglitazone improves endothelial function in patients with type 2 diabetes treated with insulin

“…18 In these patients, impaired endothelial function may be attributed to a combination of factors, such as long duration of T2DM with poor glycaemic control and insulin resistance, uncontrolled dyslipidaemia and hypertension, 21 but also to the role of exogenous insulin administration, which has been suggested to exert controversial actions on vessels. [21][22][23] In addition, most studies on carotid intima-media thickness, an index of subclinical structural atherosclerosis, [24][25][26] and a recent study on coronary atherosclerosis assessed by intravascular ultrasound 27 have not shown encouraging results with rosiglitazone in T2DM patients. Thus, a relatively small improvement in severely affected FMD, induced by a low-dose regime of rosiglitazone, without a parallel control of other cardiovascular risk factors and a demonstrable benefit on structural indices of atherosclerosis, may not be sufficient to cause a concomitant improvement in cardiovascular prognosis in patients with advanced T2DM.…”

Severe HDL-c reduction during rosiglitazone therapy in an obese woman with type 2 diabetes

“…Recently the APPROACH Study (19) was released, a trial designed to assess the effect of rosiglitazone on coronary atherosclerosis progression compared to glipizide. The primary endpoint was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention in patients with an established cardiovascular history.…”