Objectives

The BARI 2D trial was designed to test treatment strategies for patients with coronary artery disease and diabetes. The goal was to address the effects of therapy on the rate of myocardial ischemia, and of insulin resistance. The study evaluated two cardiac treatment strategies (prompt revascularization vs. medical therapy alone) and two glycemic treatment strategies (insulin sensitization vs. insulin provision).

The first hypothesis was that prompt revascularization (either surgical or catheter-based) would reduce long-term rates of death and cardiovascular events, as compared with medical therapy alone. The second hypothesis was that a strategy of insulin sensitization (with a target level for glycated hemoglobin of less than 7.0%) would reduce long-term rates of death and cardiovascular events, as compared with a strategy of insulin provision.

Background

Patients with type 2 diabetes mellitus have a higher risk of cardiovascular events and death than those without diabetes. Few large, randomized trials have addressed the question of the optimal treatment for patients with diabetes and angiographically defined stable ischemic heart disease.

Among patients with diabetes, studies have indicated that increased insulin levels predict adverse outcomes and that control of hyperglycemia by reducing insulin resistance, rather than by providing insulin, might improve cardiovascular outcomes. The effectiveness of coronary revascularization in relieving angina is well established; however, its benefit in reducing the rates of subsequent myocardial infarction and death has been shown only in patients with high-risk profiles or acute coronary syndromes. Studies of coronary revascularization in patients with moderate or with mild or no symptoms have had conflicting results. Unfortunately, such trials have not focused on patients with diabetes, who are at high risk with even mild symptoms of myocardial ischemia.

Participants

From January 1, 2001, to March 31, 2005, 2368 patients were enrolled at 49 clinical sites in the United States, Canada, Brazil, Mexico, the Czech Republic, and Austria. Eligibility criteria included a diagnosis of both type 2 diabetes and coronary artery disease. All patients had to be candidates for elective percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG). Patients were excluded if they required immediate revascularization or had left main coronary disease, a creatinine level of more than 2.0 mg per deciliter (177 μmol per liter), a glycated hemoglobin level of more than 13.0%, class III or IV heart failure, or hepatic dysfunction or if they had undergone PCI or CABG within the previous 12 months.

Design

Patients were randomly assigned to two treatment strategies in a 2-by-2 factorial design. In the first strategy, patients were assigned to undergo either prompt coronary revascularization or medical therapy. In the second strategy, patients were assigned to undergo either insulin-sensitization therapy or insulin-provision therapy to achieve a target glycated hemoglobin level of less than 7.0%. Randomization was stratified according to the method of revascularization (PCI or CABG), as determined a priori by the responsible physician to be the more appropriate therapy for each patient.
Patients in the revascularization group were to undergo the procedure within 4 weeks after randomization, whereas patients in the medical-therapy group were to undergo revascularization during follow-up only if such therapy were clinically indicated by the progression of angina or the development of an acute coronary syndrome or severe ischemia. Patients in the insulin-sensitization group could receive insulin-providing drugs, and patients in the insulin-provision group could receive insulin-sensitizing drugs if the glycated hemoglobin level could not otherwise be maintained below 8.0%.

All patients were treated according to current guidelines, with a target level for glycated hemoglobin of less than 7.0%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg per deciliter (2.6 mmol per liter), and a blood pressure of 130/80 mm Hg or less. In addition, all patients received counseling regarding smoking cessation, weight loss, and regular exercise. Clinical management centers monitored and provided feedback on risk-factor control. Patients were seen monthly for the first 6 months and every 3 months thereafter.

Conclusions

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. (N Engl J Med. 2009 June 11; 360(24): 2503–2515.)

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