Management of Diabetes Mellitus in Patients With Cardiovascular Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

Abstract

ardiovascular disease is the leading cause of morbidity and mortality for patients with type 2 diabetes mellitus (T2DM), accounting for two thirds of patient deaths. In addition to traditional cardiovascular risk factors, hyperglycemia and multiple other factors associated with T2DM such as obesity, insulin resistance, and inflammation play significant roles in cardiovascular disease risk. 1 Patients with diabetes mellitus have derived less benefit from multiple preventive and interventional advances. Indeed, in the Bypass Angioplasty Revascularization Investigation (BARI) trial, angioplasty appeared to provide very little benefit for patients with diabetes mellitus, 2 a finding supported by a meta-analysis of randomized interventional trials, 3 although modern revascularization techniques with the use of drug-eluting stents were not yet widely utilized.Therefore, the questions addressed in the BARI 2 Diabetes (BARI 2D) trial are of particular importance in determining optimal treatments to prevent mortality and major cardiovascular events in patients with T2DM and stable ischemic heart disease. Both prompt revascularization compared with intensive medical therapy alone or with delayed revascularization, and insulin-sensitization compared with insulin-provisional therapeutic strategies were evaluated in 2368 patients over 5 years with the use of a 2ϫ2 randomized factorial trial design. 4 With recognition of the cardiovascular benefits of optimal management of diabetes mellitus and cardiovascular risk factors in patients with diabetes mellitus, 5 the BARI 2D study was performed with guideline-driven targets for lipids, blood pressure, and aspirin use. Medical Therapy Compared With Prompt RevascularizationFirst, in a comparison of prompt revascularization with intensive medical therapy alone or with delayed revascularization, similar survival (88.3% versus 87.8%; Pϭ0.97) and freedom from cardiovascular event rates (77.2% versus 75.9%; Pϭ0.70) were demonstrated. However, a high proportion (42%) of subjects initially randomized to medical intervention received delayed revascularization. These findings extend those of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, in which an initial management strategy of percutaneous coronary intervention (PCI) when added to optimal medical therapy did not reduce mortality or cardiovascular event rates, although only approximately one third of patients in this trial had diabetes mellitus. 6 Taken together, these trials support the use of optimal medical therapy for those with diabetes mellitus and stable coronary artery disease who prefer not to have an invasive procedure. Furthermore, because the treating cardiologist a priori selected the revascularization method, either coronary artery bypass grafting (CABG) or PCI, on the basis of clinical and angiographic factors, patients randomized to CABG compared with PCI more frequently had 3-vessel disease and proximal left anterior descending artery lesions and had more total occlusions...

Impact of Critical Limb Ischemia on Long-Term Cardiac Mortality in Diabetic Patients Undergoing Percutaneous Coronary Revascularization

“…The cardiac mortality of 6% at 4 years observed among PCI patients was similar to that reported for stable CAD patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (24), whereas the rate of 9% among PCI-CLI patients was substantially lower than previously reported rates. Indeed, a total mortality of 50%, a cardiac mortality of 31%, and a major amputation rate of 13% at a mean follow-up of 5.9 years were reported by Faglia et al (15) in 564 consecutive CLI patients.…”

Determinants of evolving metabolic and cardiovascular benefit/risk profiles of rosiglitazone therapy during the natural history of diabetes: molecular mechanisms in the context of integrated pathophysiology

“…Further analysis enlightened the fact that in the OMT group patients treated with insulin-sensitizing therapy had higher HDL cholesterol levels, less weight gain, less frequent severe hyperglycemia, and lower Hb A 1c levels compared with patients treated with insulin provisional therapy (64). Moreover, data analysis by other investigators found equal effectiveness of OMT or PCI revascularization strategy in physical and psychological recovery of T2DM patients (17).…”

Diabetes mellitus and the heart

“…Within the entire population, no difference in major cardiovascular events was noted between strategies, although a secondary endpoint of improved cardiovascular events in the (higher risk) CABG arm was noted with insulin‐sensitising therapy (56). The interpretation and clinical application of these findings are further clouded by methodological issues (90) and concerns raised by other clinical trials regarding the cardiovascular risk of the thiazolidinedione, rosiglitazone. More specifically, a body of evidence suggests increased major cardiovascular events in patients receiving rosiglitazone (91), although this appears not to be a class‐specific effect as pioglitazone may improve cardiovascular outcome (92)).…”