About BARI 2D
Type 2 diabetes mellitus is one of the strongest risk factors for heart disease, lesser quality of life, and death.
In addition to the enormous toll in human suffering, diabetes places an economic burden approaching 100 billion dollars annually on the U.S. health care system. Despite the well known poorer outcomes for patients who have both diabetes and heart disease, the best treatment for this large group of people is not evident.
Coronary revascularization, such as bypass surgery or inserting stents, has not been directly shown to be better than intensive medical management of heart disease if blood sugars, blood pressure, and lipids are well controlled. Moreover, while efforts to lower HbA1c, a measure of how well blood sugar is in control in patients with Type 2 diabetes mellitus in terms of fewer microvascular complications, the best treatment with regard to macrovascular outcome (such as heart attacks) is not known.
BARI 2D, a multicenter randomized trial was designed to determine in patients with Type 2 diabetes and stable heart disease whether:
1) elective coronary revascularization combined with aggressive medical therapy is better for patients compared to aggressive medical therapy with revascularization only if symptoms get worse; and whether
2) providing more insulin (through giving insulin or medication that allows the body to make more insulin), is better for patients than giving medications that increase patients’ ability to better use the insulin their bodies already make (reducing insulin resistance) with a target HbA1c level of less than 7.0% for each group.
BARI 2D was funded largely by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes, Digestive and Kidney Diseases with major financial support from GlaxoSmithKline and significant donations from other pharmaceutical sponsors. To see a complete list of the sponsors, click here. The trial was directed by the BARI 2D Coordinating Center at the University of Pittsburgh and an Operations Committee.
BARI 2D enrolled 2368 patients at 49 sites in 6 countries. Each patient was assigned to either a prompt revascularization with intensive medical management or to start on medications alone, with the chance to receive a revascularization at any time during the trial if symptoms got worse. Each patient was also assigned to either insulin providing or insulin sensitizing drugs to manage their diabetes.
Only patients with known type 2 diabetes and heart disease that could be treated appropriately with a revascularization OR medical therapy alone were eligible for the trial. Patients entered the study between January 2001 – March 2005 and were followed for an average of five years. When a patient entered the study, physicians first decided whether that patient should receive stenting or bypass surgery. The patient then received their randomization assignment. Follow-up ended November 2008. BARI 2D is a standard-of-care study, meaning that any of the treatments or medications given might be prescribed by physicians around the world for a patient with these same health issues. New products approved by the FDA and new research findings that would not interfere with the treatments were added during the study (for example, drug-eluting stents) so that BARI 2D could provide the best state-of-the-art treatment to patients in the “real world”.
All patients were treated in BARI 2D for both their diabetes and heart disease, as well as other risk factors that might effect those diseases, regardess of which group they were in.
“Diabetes-specific” complications including retinopathy, nephropathy, neuropathy, and peripheral vascular disease were monitored regularly. Tests, blood samples, urine samples, and treatment cost data were obtained periodically through the trial and examined by experts at 7 central laboratories and other research partners. Experts on risk factors routinely oversaw treatments of all patients at 4 central management centers. A panel of independent experts reviewed data every six months to make sure that all patients were receiving safe care.
Every clinical trial must decide on conditions or events, known as endpoints, that can be counted when the study is over that will identify which treatments are the best. In BARI 2D, the primary endpoint was death. Other events were tracked including heart attacks, strokes, and chest pain.
In 2009, BARI 2D began analyzing and publishing outcomes of the trial. In addition to clinical outcomes, total medical costs were analyzed.