ADA 2009: Mortality Risk Equal With Early Intervention or Drug Therapy in Diabetics With Stable CVD

Martha Kerr

June 07, 2009

June 7, 2009 (New Orleans, Louisiana) — Results of the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) show that mortality risk is the same for patients with type 2 diabetes and stable ischemic heart disease whether they are managed with optimal medical therapy, coronary artery bypass graft surgery (CABG), or percutaneous coronary intervention (PCI).

However, CABG was associated with a reduction in risk for cardiovascular events, primarily nonfatal myocardial infarction, compared with intensive medical management.

Results were announced here today at the American Diabetes Association (ADA) 69th Scientific Sessions and simultaneously published online in the New England Journal of Medicine. The study will appear in the June 11 print issue.

BARI 2D findings were presented by coinvestigators Trevor Orchard, MD, a diabetologist and professor of epidemiology, medicine and pediatrics and medical director of the Nutrition Lipid Program at the University of Pittsburgh in Pennsylvania, and Robert L. Frye, MD, a cardiologist and professor of medicine in the Department of Cardiovascular Diseases at the Mayo Clinic in Rochester, Minnesota.

BARI 2D involved 2368 patients with type 2 diabetes and stable ischemic heart disease who were randomly assigned to early revascularization plus intensive medical therapy or intensive medical therapy alone. Patients were stratified according to whether they received insulin-provision therapy — an insulin secretogogue or insulin — or insulin-sensitization therapy.

Patients in the intervention group were assigned to either CABG or PCI, according to whichever was most appropriate. Patients assigned to CABG were higher risk. "It would not have been appropriate to compare these 2 groups," Dr. Orchard noted. "They were very different populations." Instead, those undergoing revascularization were compared with those receiving optimal medical therapy.

Survival rates at 5 years were 88.3% in the revascularization group and 87.8% in the medical therapy group (P = .97).

The 5-year survival rate was 88.2% in the insulin-sensitization group and 87.9% among patients who received insulin-provision therapy (P = .89).

Major cardiovascular event rates were similar in all 4 patient groups. Five-year event rates were 77.2% with revascularization and 75.9% with medical therapy (P = .70) and 77.7% with insulin sensitization and 75.4% with those taking insulin (P = .13).

However, the event rate was significantly lower in 1 subgroup. Patients randomized to both CABG and insulin sensitization therapy had "...a significantly lower rate of major cardiovascular events [primarily nonfatal myocardial infarction] than any of the other 3 treatment combination groups," the BARI 2D investigators reported.

Rates were 22.4% with revascularization and 30.5% with medical therapy at 5 years among those receiving insulin sensitization therapy (P = .01).

Severe hypoglycemia was significantly more frequent in the group that received insulin-provision therapy (9.2%) compared with those that received insulin-sensitization therapy (5.9%; P = .003).

The findings are not likely to change clinical practice, the BARI 2D investigators said.

"From the diabetes perspective, we can be assured that insulin sensitization drugs are not harmful and there is in fact a suggestion of benefit," Dr. Orchard said. The insulin-sensitizing agents were associated with less weight gain and with fewer episodes of hypoglycemia than insulin-provision therapy.

"From the cardiologist's point of view, we have identified a group of high-risk patients with extensive cardiovascular disease who benefit from early revascularization. For lower-risk patients, they can be maintained safely on medical therapy until their condition changes," Dr. Frye said. "These findings are consistent with the COURAGE findings," he told Medscape Diabetes & Endocrinology.

"But nothing stays fixed for 5 years in patients with diabetes and heart disease," Dr. Frye added. "As they develop more angina, more episodes of ischemia on stress testing or if the features change...physicians will have to use their clinical judgment on when to perform revascularization."

"Diabetes is not static. Things will change as beta cells die and the disease progresses," Dr. Orchard commented.

All patients in BARI 2D received intensive risk factor modification with weight loss, dietary intervention, lipid-lowering therapy, and other interventions. "That's why the event rates were so low, and they were low in all of the groups," Dr Orchard pointed out. "We don't think of it as a lack of benefit. It's not the procedure, it's the risks," he asserted.

"I am really impressed with how the specialists in BARI worked together," said ADA spokeswoman Susan McLaughlin, BS, RD, CDE, CPT, president of Health Care and Education at the ADA. "This was a comprehensive, coordinated program."

Ms. McLaughlin told Medscape Diabetes & Endocrinology that "this reinforces the importance of diet and exercise in maintaining quality of life and from keeping patients from having to undergo revascularization in the first place."

BARI 2D was supported by funding from the National Institutes of Health. Some of the study authors report serving on advisory boards for Axio, Sanofi-Aventis, and Schering-Plough; receiving consulting and/or lecture fees from AstraZeneca, Blue Cross Blue Shield Technology Evaluation Center, CV Therapeutics, Eli Lilly, GE Healthcare, GlaxoSmithKline, Merck, Sanofi-Aventis, and Takeda; grant support from Amgen, Aviir, Corcept Therapeutics, Eli Lilly, Tercica, and VeraLight; and having an equity interest in Amgen and Bristol-Myers Squibb.

American Diabetes Association (ADA) 69th Scientific Sessions: Symposium: Results of the BARI 2D Clinical Trial. Presented June 7, 2009.

N Engl J Med. 2009;360:2503-2515.