• Diabetes Mellitus Clinical Trials
• Coronary Artery Disease
• Interventional Techniques & Devices

For patients with type 2 diabetes and stable coronary artery disease (CAD), intensive medical therapy (IMT) provides similar protection against myocardial infarction (MI) and cardiac death compared with percutaneous coronary intervention (PCI) but is not as effective as coronary artery bypass grafting (CABG) among patients with more extensive CAD, according to new findings from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial (NCT00006305).

The BARI 2D trial was designed to compare treatment strategies for patients with type 2 diabetes, ischemic CAD, and no history of CABG or PCI within the last 12 months. Specifically, BARI 2D involved 2 comparisons: prompt revascularization versus IMT with delayed revascularization, if needed, and insulin sensitization (IS) or insulin provision (IP) therapy with a target HbA1c level of <7.0%.

Prior to randomization, the treating physician recommended a form of revascularization based on clinical and angiographic factors. Candidates for PCI (n=1605) were randomly assigned to treatment with PCI or IMT, and candidates for CABG (n=763) were randomly assigned to treatment with CABG or IMT. All patients underwent a second randomization to IS or IP therapy for glycemic control. Investigators stratified all endpoints by revascularization group, because it was assumed that patients who were candidates for CABG had higher baseline risk than those who were candidates for PCI.

The BARI 2D investigators previously reported no significant differences in the primary endpoint of all-cause mortality or in the principal secondary endpoint of all-cause death/MI/stroke between revascularization and IMT or between strategies of IS and IP. However, in the CABG group, early revascularization significantly reduced major cardiovascular events (22.4% vs 30.5%; p=0.02), primarily due to a reduction in MI in patients within the IS strategy (7.4% vs 14.6%) [Frye RL et al. N Engl J Med 2009].

Bernard R. Chaitman, MD, St. Louis University School of Medicine, St. Louis, MO, presented data on additional secondary endpoints, including MI and cardiac death. Overall, the 5-year cardiac mortality rates were similar in the revascularization and IMT groups (5.9% vs 5.7%; p=0.38) and in the IS and IP groups (5.7% vs 6.0%; p=0.76). However, important differences in secondary endpoints emerged when patients were evaluated according to revascularization strata.

Among patients who were candidates for PCI upon study enrollment, there was no difference between revascularization plus IMT and IMT alone in the risk of MI (12.3% vs 12.6%; p=0.42) or cardiac death (5.0% vs 4.2%; p=0.16). Moreover, the combined endpoint of cardiac death or MI favored treatment with IMT alone (16.0% vs 14.2%; p=0.05). In the PCI strata, there were no significant interactions between revascularization versus IMT and IP versus IS for MI, cardiac death, or the combined endpoint of cardiac death or MI.

By comparison, among patients in the CABG group, the risk of MI was significantly lower following treatment with revascularization plus IMT compared with IMT alone (10.0% vs 17.6%; p=0.003). Revascularization plus IMT also reduced the risk of the composite endpoints of all-cause death or MI (21.1% vs 29.2%; p=0.01) and cardiac death or MI (15.8% vs 21.9%; p=0.03) relative to IMT alone.

Whereas CABG reduced the risk of MI relative to IMT by 68% among patients who were treated with IS (HR, 0.32; p=0.001), early CABG did not protect against MI in patients who were treated with IP (HR, 0.79; p=0.40). Similarly, CABG reduced the combined endpoint of cardiac death or MI relative to IMT only in the IS group (HR, 0.41; p=0.0002), not in the IP group (HR, 1.03; p=0.91).

Findings from BARI 2D suggest that the optimal treatment strategy may depend on the extent and severity of CAD. “In many patients with type 2 diabetes and stable ischemic CAD, an initial strategy of IMT should be considered and does not require immediate PCI to prevent cardiac death or MI when angina symptoms are controlled,” Dr. Chaitman said. “In patients with more extensive coronary disease, a strategy of prompt CABG, intensive medical therapy, and insulin sensitization therapy should be considered the preferred strategy to reduce the incidence of spontaneous MI,” he concluded.

• © 2009 MD Conference Express