The long-awaited results of the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study, a multicenter trial led by the University of Pittsburgh Graduate School of Public Health, were reported at a symposium at the American Diabetes Association's 69th Scientific Sessions and published simultaneously in the New England Journal of Medicine.

"In combining the two revascularization approaches, we found that prompt revascularization did not hold any advantage over intensive medical therapy alone with regard to total mortality," said Trevor Orchard, M.D., Professor of Epidemiology, University of Pittsburgh Graduate School of Public Health and Director of the Lipid Management Center of BARI 2D. And yet, he added, "Prompt coronary artery bypass surgery, compared to intensive medical therapy alone, had significantly better outcomes when cardiovascular events were considered in addition to death." A large part of this benefit consisted of a reduction in non-fatal myocardial infarction, never before shown with bypass surgery.

The landmark study evaluated both a cardiovascular treatment approach as well as a diabetes control approach in 2,368 persons with type 2 diabetes and stable coronary artery disease (CAD) to reduce deaths or deaths and cardiovascular events (myocardial infarction and stroke) combined. The first component compared intensive medical treatment with prompt coronary revascularization by either bypass surgery or angioplasty to intensive medical treatment alone. The two coronary revascularization procedures were not compared to each other; rather, each treatment group was independently compared to its own control group receiving intensive medical therapy alone. The second component compared whether controlling diabetes with drugs to make insulin work better (insulin sensitization) had an advantage for heart health or survival compared to using a strategy emphasizing drugs increasing insulin itself (insulin provision).

The entry point to BARI 2D was referral for an angiogram due to evidence of ischemia, such as angina or a positive exercise stress test. After an angiogram, a cardiologist reviewed the results and clinical picture and determined the patient's suitability for inclusion in BARI 2D. If the cardiologist recommended either angioplasty or bypass surgery, yet considered intensive medical therapy a suitable option, the patient was deemed a candidate for BARI 2D. If the patient chose to enter the trial, he or she was randomly assigned to the revascularization approach recommended by the cardiologist or to intensive medical therapy.

Overall, researchers found that after an average follow up of five years, there were no differences in mortality rates nor in cardiovascular events between either type of early coronary revascularization compared to medical therapy alone. However, among the subgroup of participants who were pre-identified as candidates for coronary bypass surgery, the group who received prompt surgery had significantly fewer heart attacks or strokes compared to those who initially received intensive medical therapy alone.

Another major question asked was whether the glycemic strategy used would affect outcomes. To address this, the same 2,368 patients were simultaneously randomized to one of two different strategies for glucose control: (1) insulin-providing medications including insulin itself and/or drugs that stimulate the body to produce its own insulin versus (2) insulin-sensitizing drugs that work to lower the body's resistance to its own insulin. These two drug strategies attack two different problems in type 2 diabetes.

Insulin-providing and insulin-sensitizing drugs generally yielded similar results with regard to mortality and cardiovascular events. In contrast to results of some prior studies, no increase in heart attacks was observed in patients receiving rosiglitazone, one of the two major medications used in the insulin-sensitizing treatment arm of BARI 2D. The investigators also noted that the benefit of early bypass surgery was largely seen in patients who were also treated primarily with insulin-sensitizing drugs. "Although this type of interaction was not a major study question and thus should be viewed as preliminary, it strengthens the notion that reducing insulin resistance is a good way to treat type 2 diabetes," said Orchard.

"BARI 2D results further inform the clinical management of type 2 diabetes in patients with stable coronary artery disease and ischemia, and strengthen the choice of early coronary artery bypass surgery over medical therapy alone in those who are appropriate candidates for bypass surgery," said Saul M. Genuth, M.D., Professor of Medicine, Case Western Reserve University and Director of the Diabetes Management Center of BARI 2D. "Some of the observations also support the concurrent use of glycemic management aimed at reducing insulin resistance."

"Until now, we have not known whether any revascularization approach is beneficial above and beyond intensive medical therapy for this type of patient, even if you apply absolutely everything that you can do with such medical therapy," said Genuth. "We have been spending a lot of money and placing patients at some risk with these procedures without knowing whether or not we are actually saving lives compared to medical therapy." Now, five-year follow-up data are available to help answer these questions.

In addition to Dr. Orchard, speakers at the symposium included Sheryl F. Kelsey, Ph.D., Professor of Epidemiology, University of Pittsburgh Graduate School of Public Health, and Principal Investigator of BARI 2D, and Robert L. Frye, M.D., Professor of Cardiovascular Medicine, Mayo Clinic College of Medicine, and BARI 2D study chairman.

The coordinating center for BARI 2D was located in the Epidemiology Data Center at the University of Pittsburgh Graduate School of Public Health. It was responsible for collecting data from 49 clinical sites and centralized reading centers, performing statistical analyses of the data, and reporting on study progress to the Data Safety and Monitoring Board, appointed by the National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which were the sponsors of the study. NHLBI and NIDDK are both components of the National Institutes of Health.