The Results of the BARI 2D have finally been published. This study planned to recruit 2,800 patients. However, recruitment took longer than anticipated, so in 2005 the follow-up period was extended by 1.5 years in the attempt to compensate for premature study interruption (2,368 patients were finally recruited). The average follow up was 5.3 years, and unfortunately only 2194 patients (92.7%) completed the study as designed.
Eligible patients were patients with type 2 diabetes and stable or silent coronary artery disease defined at angiography by ≥50% stenosis of a major epicardial coronary artery associated with a positive stress test or ≥70% stenosis of a major epicardial coronary artery and classic angina.
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. Unfortunately, authors fail to report the number of screened patients over those who were finally recruited.
Patients were randomly assigned to two treatment strategies in a 2by2 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.
Thus, as a consequence, the patients for whom CABG was pre-specified as the intended method of revascularization had more extensive coronary disease, with significantly more three-vessel disease, proximal disease of the left anterior descending artery, and chronic coronary occlusions than the patients for whom PCI was intended. Patients who were selected to undergo CABG were also more likely to have a history of myocardial infarction and less likely to have undergone previous coronary revascularization. Moreover, interestingly periprocedural myocardial infarctions that were associated with PCI and CABG required an increase in the upper limit of the normal range for creatine kinase MB of 3 times and 10 times, respectively.
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).
Authors concluded by saying that among patients with type 2 diabetes and stable ischemic heart disease receiving intensive medical therapy, there was little difference between insulin sensitization and insulin provision with respect to rates of death and cardiovascular events at 5 years. Likewise, a strategy of prompt coronary revascularization with the procedure most appropriate for the individual patient and a strategy of medical therapy led to similar clinical outcomes.
As a contrary, in an accompanying editorial, authors surprisingly conclude by saying: “when revascularization is indicated, both BARI 2D and other studies support the use of CABG as the preferred approach, unless or until future studies indicate otherwise”.
Figure: Rathes of Survival and Freedom from Major Cardiovascular Events
There was no significant difference in rates of survival between the revascularization group and the medical-therapy group (Panel A) and between the insulin-sensitization group and the insulin-provision group (Panel B). The rates of major cardiovascular events (death, myocardial infarction, or stroke) also did not differ significantly between the revascularization group and the medical therapy group (Panel C) or between the insulin-sensitization group and the insulin-provision group (Panel D).