Abstract
Background-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 (-0.64%; 95% confidence interval,-1.46 to 0.17; P=0.12). The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide (-5.1 mm3; 95% confidence interval,-10.0 to-0.3; P=0.04); however, no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment (-1.7 mm3; 95% confidence interval,-3.9 to 0.5; P=0.13). 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1176-1187 |
| Number of pages | 12 |
| Journal | Circulation |
| Volume | 121 |
| Issue number | 10 |
| DOIs | |
| State | Published - Mar 16 2010 |
Funding
This study was supported by GlaxoSmithKline. The sponsor participated in the design of the study and provided logistical support during the trial. Monitoring of the study was performed by the sponsor, which also maintained the trial database. Statistical analyses of the primary and secondary end points were independently performed by both the sponsor and an independent academic statistician, and the results were cross-checked. Manuscript development was led by the corresponding author in collaboration with the other authors. Authors employed by the sponsor reviewed the manuscript and suggested changes, but the final decision on content was retained by the academic authors. Dr Gerstein has received honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Lilly, Merck, Novo Nordisk, and Sanofi-Aventis and grants from GlaxoSmithKline, King, Merck, Novo Nordisk, and Sanofi-Aventis. Dr Ratner has received grants from AstraZeneca, Bayhill Therapeutics, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novo Nordisk, Pfizer, Takeda, and Ver-alight; served as an advisor to Amylin, AstraZeneca, Eli Lilly, GlaxoSmithKline, Lifescan, Novo Nordisk, Roche, Sanofi-Aventis, Sirtris, Takeda, and Tethys; and holds stock (>$10 000 value) in Abbott, Johnson and Johnson, and Merck. Dr Cannon has received grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Merck, and the Merck/Schering
Keywords
- Atherosclerosis
- Intravascular
- Rosiglitazone
- Type 2 diabetes mellitus
- Ultrasonography
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
