BARI 2D Trial Published

June 11, 2009—In the New England Journal of Medicine, Robert L. Frye, MD, et al published findings from the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D), which was sponsored by the National Institutes of Health (2009;360:2503-2515). The BARI 2D findings were also presented at the American Diabetes Association's 69th annual scientific sessions, which were held June 5 to 9 in New Orleans, Louisiana.

According to the BARI 2D group investigators, optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established. In the study, the investigators randomly assigned 2,368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. The primary endpoints were the rate of death and the rate of major cardiovascular events (a composite of death, myocardial infarction, or stroke). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) as the more appropriate intervention.

The investigators reported in the New England Journal of Medicine that at 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical therapy group (87.8%; P = .97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%; P = .89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P = .7); and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P = .13). In the PCI stratum, there was no significant difference in primary endpoints between the revascularization group and the medical therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical therapy group (30.5%; P = .01; P = .002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%; P = .003).

Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision, the investigators concluded.

On June 8, the Society for Cardiology and Angiographic Interventions (SCAI) commented on the BARI 2D trial findings. The complete statement is available on the SCAI Web site, www.scai.org.

SCAI stated that BARI 2D is a useful and focused trial that builds on the body of scientific knowledge physicians use to provide the best possible care for diabetic patients with chronic stable angina and to evaluate their treatment options. The society encourages health care providers to apply the findings of BARI 2D, when appropriate, to their patients, as studied in this trial. BARI 2D specifically applies to those with carefully controlled diabetes, multivessel but stable coronary artery disease (CAD), and few heart disease symptoms. This trial does not answer the question of whether all patients with diabetes and multivessel CAD might be better treated with optimal medical therapy plus either PCI or CABG. Because the BARI 2D study enrolled a very small subset of CAD patients with diabetes, SCAI stated that it looks forward to additional data from the upcoming FREEDOM trial, which may shed more light on revascularization options for this growing patient population.

"Physicians should understand the patients in the BARI 2D study are highly selected and represent only a very small slice of diabetes and heart disease patients. More research is needed on the larger diabetic population," stated SCAI President Steven R. Bailey, MD. "Unfortunately, the majority of the BARI 2D patients did not receive drug-eluting stents, which have been shown to be superior to bare-metal stents for diabetic patients. The standard of care has evolved since BARI 2D was initiated, and many of the early patients in the trial did not receive the care we now know to be most effective."

"It's important to note that in a real-world setting, patients' blood sugar levels are not so closely monitored to maintain optimal levels as in this study," added Robert Chilton, DO. "The patients I see with diabetes and heart disease frequently have difficulty complying with a drug regimen that includes upwards of 10 pills per day, often coupled with insulin injection. Not surprisingly, noncompliance can quickly lead to deteriorating health and should be carefully considered for patients who may be candidates for revascularization."