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).
OBJECTIVE
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).
Lonn
Eva M
EM
Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada. lonnem@mcmaster.ca
Gerstein
Hertzel C
HC
Sheridan
Patrick
P
Smith
Sandra
S
Diaz
Rafael
R
Mohan
Viswanathan
V
Bosch
Jackie
J
Yusuf
Salim
S
Dagenais
Gilles R
GR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000473:pathology / Q000517:prevention & control; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000627:therapeutic use*; D000077154:Rosiglitazone; D016037:Single-Blind Method; D045162:Thiazolidinediones / Q000627:therapeutic use*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D017257:Ramipril