Peroxisome Proliferator–Activated Receptor Study - PPAR Study
The goal of the trial was to evaluate treatment with the peroxisome proliferator–activated receptor (PPAR) agonist rosiglitazone compared with placebo in patients with metabolic syndrome undergoing percutaneous coronary intervention (PCI).
Patients Enrolled: 200
Mean Follow Up: 1 year
Mean Patient Age: Mean age, 59 years
Age 21-85 years undergoing elective or urgent PCI with angiographic evidence of coronary artery disease who were obese (BMI >27 kg/m2 or waist circumference >40 inches in men and >35 inches in women) and at least one of the following clinical characteristics: diagnosed or medically treated hypertension, dyslipidemia, treated hyperlipidemia, HbA1c >6.0%, or fasting glucose ≥110 mg/dl
Diabetes requiring pharmacologic treatment within 3 months; PCI within 14 days; primary PCI done for acute revascularization of an MI; clinical heart failure; anemia; current treatment with, or known intolerance to, thiazolidinediones; contraindication or sensitivity to aspirin, clopidogrel, heparin, or intravenous glycoprotein IIb/IIIa inhibitors; or renal insufficiency
CIMT progression rate on Doppler ultrasound during the 12-month follow-up
Patients were randomized in a double-blind manner to rosiglitazone (4 mg orally BID; n = 102) or placebo (n = 98). Doppler ultrasound was performed at baseline and 6 and 12 months to evaluate carotid intimal-media thickness (CIMT).
Mean body mass index (BMI) at baseline was 33 kg/m2. Patients were treated with study drug for a median of 5 minutes pre-PCI in the rosiglitazone group and 7 minutes in the placebo group. Half of the patients had single-vessel disease. Bare-metal stents were used in 87% of patients.
There was no difference in the primary endpoint of CIMT progression between the two groups using maximum CIMT (-0.02 mm/y for rosiglitazone vs. -0.003 mm/y for placebo, p = 0.42) or mean CIMT (-0.001 mm/y vs. 0.013 mm/year, p = 0.49). The composite of death, myocardial infarction (MI), or stroke at 12 months did not differ between groups (6.4% for rosiglitazone vs. 11.9% for placebo, p = 0.19).
At 1 year, increase in high-density lipoprotein (15.5% vs. 4.1%, p = 0.05) and decrease in triglycerides (-13.9% vs. 14.9%, p = 0.004) was greater in the rosiglitazone group compared with placebo. There was no difference between groups in 12-month glucose (median 98 mg/dl in both groups), insulin (13.2 vs. 10.8 micro IU/ml), or HbA1c (6% vs. 5.8%) for rosiglitazone versus placebo, respectively.
New onset diabetes was infrequent; there were no new cases in the rosiglitazone group and 3.3% of the placebo group (p = 0.081). New onset heart failure did not differ between groups (1.2% of the rosiglitazone group vs. none of the placebo group, p = 0.31), nor did change in B-natriuretic peptide at 12 months (16 vs. 44 pg/ml, p = 0.20).
Among patients with metabolic syndrome undergoing PCI, treatment with the PPAR agonist rosiglitazone was not associated with a difference in CIMT progression compared with placebo at 12 months in this pilot trial.
Patients with metabolic syndrome are at increased risk for cardiovascular events. In the PROACTIVE trial of diabetics, a different PPAR agonist, pioglitazone, was associated with a reduction in the secondary endpoint of death, MI, or stroke compared with placebo.
Additionally, in the CHICAGO study of diabetic patients, treatment with pioglitazone for 18 months was associated with a reduction in CIMT progression compared with glimepiride. It was unknown if such a benefit might be extended to nondiabetic patients with metabolic syndrome, who are at high-risk for cardiovascular events and development of new diabetes. Unlike CHICAGO, there was no difference in CIMT progression with rosiglitazone. The difference may be due to the population studied (diabetics vs. metabolic syndrome) or the therapy (pioglitazone/glimepiride vs. rosiglitazone/placebo).
In the DREAM trial, rosiglitazone was associated with a reduction in new onset diabetes in patients without diabetes, but with impaired fasting glucose. New onset diabetes in the present study of metabolic syndrome patients trended lower with rosiglitazone, but the study was small and not powered for clinical endpoints. Unlike earlier studies, no apparent increase in heart failure was observed with rosiglitazone.
Bhatt DL, Chew DP, Grines C, et al. Peroxisome proliferator–activated receptor gamma agonists for the Prevention of Adverse events following percutaneous coronary Revascularization—results of the PPAR Study. Am Heart J 2007;154:137-43.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism, Acute Heart Failure, Interventions and Coronary Artery Disease, Diet, Hypertension
Keywords: Coronary Artery Disease, Hyperlipidemias, Glucose, Sulfonylurea Compounds, Natriuretic Peptides, Waist Circumference, Obesity, Thiazolidinediones, Hypertension, Myocardial Infarction, Insulin, Stroke, Immunosuppressive Agents, Peroxisome Proliferator-Activated Receptors, Stents, Percutaneous Coronary Intervention, Metabolic Syndrome X, Body Mass Index, Metals, Heart Failure, Hypoglycemic Agents, Triglycerides, Fasting, Diabetes Mellitus
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