Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI2D)

Inclusion Criteria:

• Diagnosis of Type 2 diabetes mellitus
• Coronary arteriogram showing one or more vessels amenable to revascularization (greater than or equal to 50% stenosis)
• Objective documentation of ischemia OR subjectively documented typical angina with greater than or equal to 70% stenosis in at least one artery
• Suitability for coronary revascularization by at least one of the available methods (does not require the ability to achieve complete revascularization)
• Ability to perform all tasks related to glycemic control and risk factor management

Exclusion Criteria:

• Definite need for invasive intervention as determined by the attending cardiologist
• Prior bypass surgery (CABG) or prior catheter-based intervention within the 12 months before study entry
• Planned intervention for disease in bypass graft(s) if the patient is randomly assigned to a strategy of initial revascularization
• Class III or IV CHF
• Creatinine greater than 2.0 mg/dL
• HbA1c greater than 13%
• Need for major vascular surgery concomitant with revascularization (e.g., carotid endarterectomy)
• Left main stenosis greater than or equal to 50%
• Non-cardiac illness expected to limit survival
• Hepatic disease (ALT greater than 2 times the ULN)
• Fasting triglycerides greater than 1000 mg/dL in the presence of moderate glycemic control (HbA1c less than 9.0%)
• Current alcohol abuse
• Chronic steroid use judged to interfere with the control of diabetes, exceeding 10 mg of Prednisone per day or the equivalent
• Pregnancy, known, suspected, or planned in 5 years after study entry
• Geographically inaccessible or unable to return for follow-up
• Enrolled in a competing randomized trial or clinical study
• Unable to understand or cooperate with protocol requirements

Patients with Type 2 diabetes mellitus and CAD documented by coronary arteriography will be eligible for the trial if revascularization is not required for prompt control of severe or unstable angina. Diabetic patients who are being treated with insulin or oral hypoglycemic drugs will be eligible as well as diabetic patients treated with diet and exercise alone provided that a diagnosis of diabetes can be confirmed by record review or that a fasting plasma glucose (FPG) greater than 125/mg/dL (7.0 mmol/L) can be obtained. The determination of suitability for BARI 2D will be made by a physician-investigator at each participating institution on clinical grounds at the time of coronary angiography.

Significant CAD will be defined as at least one stenosis greater than 50%. Angina and ischemia will be assessed by use of patient self-report, physician examination, and appropriate diagnostic measures including exercise myocardial perfusion imaging, exercise echocardiography, exercise electrocardiography, and IV dipyridamole or adenosine myocardial perfusion imaging or invasively by doppler or pressure wire. Objective documentation of myocardial ischemia includes any of the following:

1. Exercise or pharmacologically-induced:

   1. Greater than or equal to 1 mm of horizontal or downsloping ST depression or elevation for greater than or equal to 60-80 milliseconds after the end of the QRS complex
   2. Myocardial perfusion defect
   3. Myocardial wall motion abnormality
2. Stabilized, prior acute coronary syndrome with CK-MB or troponin elevation or with new, greater than or equal to 0.5 mm ST depression or elevation, or T wave inversion of greater than or equal to 3 mm in 2 contiguous ECG leads
3. Doppler or pressure wire showing coronary flow reserve (CFR) less than 2.0 or fractional flow reserve (FFR) less than 0.75

Among patients without documented ischemia, only patients with stenosis greater than or equal to 70% presenting with classic anginal symptoms will be eligible for randomization.