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CLINICAL RESEARCH: CLINICAL TRIAL

Effect of Ramipril and of Rosiglitazone on Carotid Intima-Media Thickness in People With Impaired Glucose Tolerance or Impaired Fasting Glucose

STARR (STudy of Atherosclerosis with Ramipril and Rosiglitazone)

Eva M. Lonn, MD, MSc^_*,,_*, Hertzel C. Gerstein, MD, MSc^_*,, Patrick Sheridan, MSc, Sandra Smith, RDMS, Rafael Diaz, MD, Viswanathan Mohan, MD, PhD, Jackie Bosch, MSc, Salim Yusuf, DPhil^_*,, Gilles R. Dagenais, MD^|| DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) and STARR Investigators

^_* Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
Estudios Cardiologicos Latinoamerica, Rosario, Argentina
Madras Diabetes Research Foundation, Gopalapuram, Chennai, India
^|| Quebec Heart Institute/Laval Hospital, Laval University, Quebec City, Quebec, Canada

Manuscript received August 25, 2008; revised manuscript received December 19, 2008, accepted December 22, 2008.

^_* Reprint requests and correspondence: Dr. Eva M. Lonn, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada (Email: lonnem{at}mcmaster.ca).

Objectives: The aim of this study was to evaluate effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril and the thiazolidinedione (TZD) rosiglitazone on carotid intima-media thickness (CIMT) in people with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG).

Background: People with IGT and/or IFG are at increased long-term risk for cardiovascular disease. Effects of ACE inhibitors and of TZDs on vascular disease in this population are unknown.

Methods: One thousand four hundred twenty-five people with IGT and/or IFG but without cardiovascular disease or diabetes were randomized to ramipril 15 mg/day or its placebo and to rosiglitazone 8 mg/day or its placebo with a 2 x 2 factorial design. The primary study outcome was the annualized change of the aggregate maximum CIMT, computed as the average of the maximum CIMTs across 12 carotid arterial segments. The secondary study outcome was the annualized change of the mean far wall left and right common CIMT. Median follow-up was 3 years and carotid ultrasound examinations were obtained at baseline and yearly thereafter.

Results: There were no differences in the primary and secondary outcomes between the ramipril and placebo groups. Compared with placebo, rosiglitazone reduced the primary CIMT outcome, but the difference was not statistically significant (difference = 0.0027 ± 0.0015 mm/year; p = 0.08) and significantly reduced the secondary CIMT outcome (difference = 0.0043 ± 0.0017 mm/year; p = 0.01).

Conclusions: In people with IGT and/or IFG without cardiovascular disease and diabetes, treatment with ramipril had a neutral effect on CIMT, whereas rosiglitazone modestly reduced CIMT progression. (The Study of Atherosclerosis With Ramipril and Rosiglitazone; NCT00140647).

Key Words: ACE inhibitors • atherosclerosis • carotid intima-media thickness • pre-diabetes • thiazolidinediones

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CIMT = carotid intima-media thickness   CUS = carotid ultrasound   CV = cardiovascular   IFG = impaired fasting glucose   IGT = impaired glucose tolerance   TZD = thiazolidinedione

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