No advantage to revascularization over optimal medical therapy in patients with type 2 diabetes and stable CAD

June 8, 2009

Prompt revascularization holds no advantage over optimal medical therapy in terms of survival among the overall population of patients with type 2 diabetes and stable coronary artery disease (CAD).

Prompt revascularization holds no advantage over optimal medical therapy in termsof survival among the overall population of patients with type 2 diabetes and stablecoronary artery disease (CAD).

Further, there are no differences in the rates of survival and majorcardiovascular events associated with two different strategies of glycemic controlin this population.

Coronary artery bypass graft (CABG) surgery, however, is associated with areduction in major cardiovascular events, attributable to a reduction in theincidence of nonfatal myocardial infarction (MI), compared with medical therapy, sayinvestigators (pictured left) from the Bypass Angioplasty Revascularization Investigation 2 Diabetes(BARI 2D) trial.

In BARI 2D, 2,368 patients with type 2 diabetes and stable heart disease wererandomized to receive drug therapy in addition to prompt revascularization (eitherCABG or percutaneous coronary intervention [PCI] within 4 weeks after randomization)or to medical therapy alone. Patients were also randomized to one of two diabetestreatment strategies-insulin-providing therapy or insulin-sensitizingtherapy.

Patients enrolled were referred for evaluation for CAD and had documented CAD onangiography. Those randomized to revascularization had their procedure chosen bytheir physician based on the extent and/or location of their disease.

Ninety-five percent of patients in each group were being treated with statins,94% with aspirin, more than 90% with an angiotensin-converting enzyme (ACE)inhibitor or angiotensin-receptor blocker, and almost 90% with a beta blocker.

After five years of follow-up, the primary outcome-death from anycause-was nearly identical among patients randomized to revascularization ormedical therapy alone (88.3% vs 87.8%, respectively; p=0.97). There was alsono significant difference in survival between the diabetes treatmentstrategies-88.2% in the group randomized to insulin sensitizers versus 87.9%in those randomized to insulin-providing therapy (p=0.89).

"We are reassured that treatment with insulin-sensitization drugs, which havebeen concerning to a certain degree in the past, are not harmful, and this is areasonable alternative for diabetes management," says Trevor Orchard, MD,coinvestigator of BARI 2D and professor of epidemiology, medicine, and pediatrics,University of Pittsburgh, PA (pictured right). Patients on insulin-sensitizing drugs were less likely togain weight and were less likely to experience hypoglycemia in the study, headds.

In particular, thiazolidinediones such as rosiglitazone have come under scrutinyfor increasing the risk of heart failure and possibly MI.

At three years, 62% of patients assigned to insulin-sensitizing therapy weretaking thiazolidinediones and 75% were on metformin. In those assigned toinsulin-providing drugs, 61% were on insulin and 52% were on a sulfonylurea.

There was no significant difference in the occurrence of the primary endpointbetween patients who underwent PCI as part of being randomized to revascularizationand those assigned to medical therapy alone. Patients chosen to undergo CABG astheir revascularization strategy had a significantly lower rate of majorcardiovascular events-a secondary endpoint-compared with thoserandomized to medical therapy (22.4% vs 30.5%, respectively; p=0.01).

"From the cardiology perspective, the most striking finding is the identificationof a high-risk group of patients who were selected for coronary bypass primarily onthe basis of the most extensive coronary disease, who benefit from prompt coronarybypass," says Robert Frye, MD, coinvestigator and professor of medicine, MayoClinic, Rochester, MN (pictured left). "This is the first demonstration in a properly objectiverandomized trial that, in patients with mild symptoms and stable ischemic heartdisease, that coronary bypass reduces these events, which were primarily nonfatalmyocardial infarction."

About 40% of the patients assigned to medical therapy alone had worsening angina,developed severe ischemia, or had an acute coronary syndrome during follow-up thatmade revascularization clinically indicated, he notes.

The results also show that aggressive medical therapy is equally as effective asPCI in low-risk patients, a finding that is consistent with the results of COURAGE(Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation), saysDr. Frye.

More than half of the patients (56%) who underwent PCI had implantation with abare metal stent as opposed to a drug-eluting stent, which has since become thestent of choice among interventionalists. Yet Dr. Frye says that althoughdrug-eluting stents are no doubt superior to bare metal stents in preventing repeatrevascularizations, they have not been proven to reduce the incidence ofcardiovascular events or mortality.