A randomized trial of therapies for type 2 diabetes and coronary artery disease

Abstract

Background: Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.

Methods: We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.

Results: At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).

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. (ClinicalTrials.gov number, NCT00006305.)

Conflict of interest statement

Dr. Frye reports serving on advisory boards for Sanofi-Aventis and Schering-Plough; Dr. Kelsey, serving on advisory boards for Sanofi-Aventis and Axio; Dr. Orchard, receiving consulting fees from AstraZeneca, Eli Lilly, and Takeda and grant support from VeraLight and having an equity interest in Bristol-Myers Squibb; Dr. Chaitman, receiving consulting fees from Eli Lilly and lecture fees from CV Therapeutics; Dr. Genuth, receiving consulting fees from Takeda, Sanofi-Aventis, and Merck; Dr. Hlatky, receiving consulting fees from Blue Cross Blue Shield Technology Evaluation Center and GE Healthcare and grant support from Aviir; Dr. Jones, having an equity interest in Amgen; Dr. Molitch, receiving consulting and lecture fees from Sanofi-Aventis and grant support from Amgen, Eli Lilly, Tercica, and Corcept Therapeutics; and Dr. Nesto, receiving consulting and lecture fees from GlaxoSmithKline and Sanofi-Aventis. No other potential conflict of interest relevant to this article was reported.

2009 Massachusetts Medical Society

Figures

Figure 1

The flow chart depicting the BARI 2D the sequence of selecting the intended revascularization randomization stratum followed by the assignment of the randomized treatment groups.

Figure 2

The estimated percent of patients surviving in the prompt revascularization (Panel A solid line) and intensive medical (Panel A dashed line) and in the insulin sensitization (Panel B solid line) and insulin provision (Panel B dashed line) randomized treatment groups. The estimated percent of patients free of major cardiovascular events in the prompt revascularization (Panel C solid line) and intensive medical (Panel C dashed line) and in the insulin sensitization (Panel D solid line) and insulin provision (Panel D dashed line) randomized treatment groups.

Figure 3

The estimated percent of patients surviving in the prompt revascularization (solid line) and intensive medical (dashed line) randomized treatment groups within the intended PCI stratum (Panel A) and within the intended CABG stratum (Panel B). The estimated percent of patients free of major cardiovascular events in the prompt revascularization (solid line) and the intensive medical (dashed line) randomized treatment groups within the intended PCI stratum (Panel C) and within the intended CABG stratum (Panel D).