Periscope trial

Introduction

Study characteristics: ,

prospective, randomized, multicenter, double-blind trial of 543

patients with diabetes mellitus type 2 & coronary artery disease

Inclusion criteria:

• 35-85 years
• baseline hemoglobin A1c of 6-9%
• undergoing coronary angioplasty

Exclusion criteria:

• diabetes mellitus type 1
• those taking 3 or more hypoglycemic agents
• patients who had received a thiazolidinedione within the previous 12 weeks
• serum creatinine > 2 mg/dL
• serum triglyceride level greater than 500 mg/dL
• blood pressure greater than 160/100 mm Hg
• active liver disease
• left main coronary artery stenosis > 50%

Baseline characteristics:

• vital signs & laboratory values (fasting blood glucose, hemoglobin A1c, fasting serum insulin, lipid profiles, serum C-reactive protein, & serum BNP) were similar

Study:

Depending on prior therapy for diabetes, patients were randomized to either:

• glimepiride (Amaryl) 1-4 mg PO QD, ave: 2.9 mg QD
• pioglitazone (Actos) 15-45 mg PO QD, ave: 37.5 mg

Patients were allowed to receive insulin & other medications for diabetes, except a sulfonylurea or a thiazolidinedione.

> 80% of patients receiving an ACE inhibitor or ARB

~ 90% receiving lipid lowering therapy

During initial coronary angiography, intravascular ultrasound of one coronary vessel was performed. Subsequently, a follow-up intravascular ultrasound on the same coronary vessel was performed 12-18 months later, if cardiac catheterization was clinically necessary prior to the 18 month visit

Primary outcome: % percent change in atheroma volume

Secondary outcomes:

• change in average maximum atheroma thickness
• normalized total atheroma volume
• change in atheroma volume in the most diseased 10-mm subsegment of the coronary vessel

Results:

• baseline & follow-up intravascular ultrasound on a coronary vessel were only available for2/3 of the patient
• mean % atheroma volume increased by 0.73% in glimepiride group, yet decreased by 0.16% pioglitazone group
• maximum atheroma thickness increased in the glimepiride group & decreased in the pioglitazone group
• no differences for normalized total atheroma volume & change in atheroma volume in the most diseased 10-mm subsegment of the coronary vessel
• hemoglobin A1c values were lower in the pioglitazone group (6.9% vs. 7.0% for glimepiride, p = 0.04)
• mean HDL cholesterol levels increased more in the pioglitazone group (5.7 mg/dL vs 0.9 mg/dL, p < 0.001)
• serum triglyceride & C-reactive protein concentrations declined more in the pioglitazone group than the glimepiride group
• fasting insulin levels increased from baseline in patients in glimepiride group, but decreased in pioglitazone group (anticipated result based upon mechanisms of action)
• mean systolic blood pressure increased in both groups, but was smaller in pioglitazone group (0.1 vs 2.3 mmHg)
• pioglitazone group had greater mean weight gain than glimepiride group (3.6 kg vs. 1.6 kg, P < 0.001)
• pioglitazone group had % greater change in serum BNP (8.0 pg/mL vs. 0.58 pg/mL, p=0.001)
• rate of major cardiovascular adverse events was similar in the 2 groups, but the trial was not powered to detect a difference in morbidity & mortality

Conclusions:

• in patients with type 2 diabetes & coronary artery disease, treatment with pioglitazone significantly reduced the rate of coronary atherosclerosis progression compared with glimepiride

Confounders:

• although baseline blood pressure values were similar between the two groups, more patients who received glimepiride reported a history of hypertension, & more of these patients reported that they were current smokers
• in contrast, patients who received pioglitazone were more likely to have a prior history of smoking

More general terms

• clinical trial

Additional terms

• glimepiride (Amaryl)
• pioglitazone (Actos)