Cardiometabolic effects of rosiglitazone in patients with type 2 diabetes and coronary artery bypass grafts: A randomized placebo-controlled clinical trial.
OBJECTIVE
To assess the efficacy and safety of rosiglitazone on saphenous vein graft (SVG) atherosclerosis prevention and on modification of the global cardiometabolic risk profile.


RESULTS
This was a double-blind, randomized, placebo-controlled, multicenter trial which enrolled 193 post-CABG patients with type 2 diabetes. Atherosclerosis changes in one SVG were assessed with intravascular ultrasound at baseline and at 12 months. Serial cardiometabolic assessments were performed. At baseline, both groups had mean HbA(1C)<7%, LDL-cholesterol (LDL-C)<2.3 mmol/l, HDL-cholesterol (HDL-C)>1.0 mmol/l and blood pressure<130/75 mmHg. After 12 months, plaque volume in SVG had increased (median [interquartile range]) by 7.7 mm(3) (-17.2 to 37.9) in the placebo group and decreased by 0.3mm(3) (-19.1 to 22.3) in the rosiglitazone group (P=0.22). Compared to placebo, rosiglitazone treated patients had a higher (mean + or - SD) body weight (89 + or - 15 kg vs. 84 + or - 15 kg, P=0.02) at the end of the study, mostly related to an increment in subcutaneous adipose tissue. Rosiglitazone treated patients also displayed further improvements in glycemic control compared to placebo (HbA(1C): 6.4 + or - 0.7% vs. 7.0 + or - 0.9%, P<0.001) as well as in several cardiometabolic parameters such as lipids (HDL-C: 1.16 + or - 0.28 mmol/l vs. 1.06 + or - 0.23 mmol/l, P=0.003), inflammatory profile (C-reactive protein: 0.92 mg/l [0.51-1.56] vs. 1.37 mg/l [0.79-3.08], P=0.02), and adiponectin levels (11.1 microg/ml [8.19-17.9] vs. 4.65 microg/ml [3.27-7.15], P<0.001). There was no significant difference in the incidence of serious adverse cardiovascular events. However, more patients in the rosiglitazone group had peripheral oedema (33% vs. 18%, P=0.0019).


CONCLUSIONS
After a 12-month follow-up, we found no evidence for a statistically significant effect of rosiglitazone on SVG atherosclerosis whereas significant effects on glycemic control and on the cardiometabolic risk profile appeared to be modulated in part by changes in subcutaneous adiposity.
Bertrand
Olivier F
OF
Quebec Heart-Lung Institute, Québec, Canada. Olivier.bertrand@crhl.ulaval.ca
Poirier
Paul
P
Rodés-Cabau
Josep
J
Rinfret
Stéphane
S
Title
Lawrence M
LM
Dzavik
Vladimir
V
Natarajan
Madhu
M
Angel
Juan
J
Batalla
Nuria
N
Alméras
Natalie
N
Costerousse
Olivier
O
De Larochellière
Robert
R
Roy
Louis
L
Després
Jean-Pierre
JP
D000368:Aged; D050197:Atherosclerosis / Q000473:pathology*; D002097:C-Reactive Protein; D008078:Cholesterol, LDL / Q000378:metabolism; D001026:Coronary Artery Bypass / Q000379:methods*; D003324:Coronary Artery Disease / Q000150:complications* / Q000628:therapy; D048909:Diabetes Complications / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000096:biosynthesis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012306:Risk; D000077154:Rosiglitazone; D012501:Saphenous Vein / Q000473:pathology / Q000637:transplantation*; D045162:Thiazolidinediones / Q000494:pharmacology*
D002097:C-Reactive Protein; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010919:Placebos; D000077154:Rosiglitazone; D045162:Thiazolidinediones