The Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: impact of treatment strategy on cardiac mortality and myocardial infarction

Abstract

Background: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI).

Methods and results: Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P=0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P=0.76). In the coronary artery bypass grafting stratum (n=763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P=0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P=0.010) and cardiac death or MI (P=0.03) were also less frequent. Reduction in MI (P=0.001) and cardiac death/MI (P=0.002) was significant only in the insulin sensitization group.

Conclusions: In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI.

Trial registration: ClinicalTrials.gov NCT00006305.

Figure 1

Rates of All-Cause Death or Cardiac Death and of Death/MI or Cardiac Death/MI. There were no significant differences in the rates of death or cardiac death between the revascularization group and the medical-therapy group (Top Left Panel) or in the rates of the composite endpoint of all-cause death/MI or cardiac death/MI (Top Right Panel). Similar results were seen between the insulin-sensitization group and the insulin-provision group (Bottom Panels).

Figure 2

Rates of All-Cause Death or Cardiac Death and of Death/MI or Cardiac Death/MI, According to PCI and CABG Strata. There were no significant differences in the rates of all-cause death or cardiac death between the revascularization group and the medical-therapy group among patients who were selected for the percutaneous coronary intervention (PCI) stratum (Top Left Panel) or in the rates of the composite endpoint of all-cause death/MI or cardiac death/MI (Top Right Panel). Among patients who were selected for the coronary artery bypass strategy (CABG) stratum, the rates for all-cause or cardiac mortality were not significantly different (Lower Left Panel), but the rates for all-cause death free of MI (p=0.009) or cardiac death free of MI (p=0.03) were significantly better than in the medical-therapy group (Lower Right Panel).

Figure 3

Time to First Myocardial Infarction (MI) in the PCI Stratum (Top Panel) and in the CABG Stratum (lower Panel). The incremental risk of myocardial infarction was continuous over time in the Intensive Medical Therapy Groups. In the CABG stratum, the difference in myocardial infarction rates between initial REV with CABG compared to an initial Intensive Medical Therapy strategy was significant (p=0.003).

Figure 4

Time to cardiac death according to the 4 initial treatment strategies (top panel) and in the PCI stratum (lower left panel) or CABG stratum (lower right panel). IS–R indicates revascularization IS group; IP–R, revascularization IP group; IS–M, IMT IS group; and IP–M, IMT IP group.

Figure 5

Time to First Myocardial Infarction (MI) (Top Panel) according to the initial treatment strategy and in the PCI stratum (lower left panel) and CABG Stratum (lower right Panel). A marked reduction in MI incidence is seen in the IS-R treatment group. The relative risk of MI for REV/IMT was significantly different (p=0.001) in the IS group whereas the difference was not significant in the IP group. IS–R indicates revascularization IS group; IP–R, revascularization IP group; IS–M, IMT IS group; and IP–M, IMT IP group.