Clinical and angiographic risk stratification and differential impact on treatment outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial

Abstract

Background: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata.

Methods and results: An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery-selected patients in the highest angiographic risk tertile (P=0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization; P=0.010; hazard ratio=2.10; P=0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum.

Conclusion: Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

Dr. Brooks has a research grant from Sanofi. Dr. Chaitman is on the speakers bureau for Gilead Pharmaceuticals and is a consultant for Merck, Pfizer, Eli Lilly, Takeda and Roche. Dr. Nesto is a consultant for GSK, Merck, and Sanofi. Dr. Feit is a shareholder of Johnson and Johnson, The Medicines Company, Boston Scientific, and Eli Lilly. Dr. Gersh is a consultant for Ortho-McNeil Janssen Scientific Affairs, Amorcyte, GE Healthcare, St. Jude Medical, Medispec Limited, Merck & Company, and Boston Scientific. Dr. Krone receives honorarium from Boston Scientific, is an expert witness for Sichmeller, Groves, Bowman, Sulak, and is a consultant for Janssen and Rivaroxaban. Dr. Garber has a research grant with Novo Nordisk insulin and liraglutide studies, is on the speakers bureau for Merck, Novo Nordisk, Santarus, Daiichi Sankyo; Honoraria for Nova Nordisk, Merck, Daiichi Sankyo, Takeda, Boehringer Ingelheim, LipoScience, is an expert witness for Nova Nordisk and Astra-Zeneca and serves on the AACE Board of Directors. Dr. Spencer King is on the speakers bureau for Network for continuing medical education and is a consultant for Merck, Wyeth Pharmaceuticals, CeloNova Biosciences, and Contact Surgical. Dr. Davidson is a consultant for Abbott. Dr. Ikeno has received honoraria from Medtronics, Abbott, Terumo Pharmaceuticals, and Asahi Intecc Co.

Figures

Figure 1

The hazard ratio of death/MI/stroke for medical therapy vs. prompt revascularization by baseline angiographic subgroups stratified by intended revascularization. The number of patients and the 5-Year Kaplan-Meier estimated cumulative event rates for patients randomized to medical (MED) and REV in each of the baseline subgroups are reported. The hazard ratio for MED versus REV (diamond) and its 95% confidence interval is plotted using a log scale. The vertical line represents a hazard ratio (HR) of 1 (no randomized treatment effect). The interaction p-value is a test of equality of the HRs among the levels of the subgroup variable. The left panel shows results for patients in the PCI stratum and the right panel shows results for patients in the CABG stratum.

Figure 2

Risk of cardiovascular events in BARI 2D by Framingham and angiographic risk score category. The columns on the left represent the 5-year Kaplan–Meier event rate of death for low risk and high risk patient groups as defined by the Framingham clinical score and the BARI 2D angiographic score. The columns on the right represent the 5-year Kaplan-Meier event rate of the composite outcome of death, MI and stroke. The p-values indicate the significance of the log-rank statistic comparing the risk of events in the low and the high risk groups.

Figure 3

Death, MI or stroke by angiographic risk score category and intended revascularization stratum. Each panel shows the Kaplan-Meier event rates for the composite outcome death/MI/stroke for patients randomized to Medical Therapy (MED blue) and Prompt Revascularization (REV red) with the log-rank p-value. Patients are stratified according to intended revascularization stratum and angiographic risk score. Panel a) PCI stratum, low angiographic risk, b) PCI stratum, high angiographic risk, c) CABG stratum low angiographic risk, d) CABG stratum, high angiographic risk

Figure 4

The HR of death/MI/stroke for MED therapy vs. prompt revascularization by angiographic and Framingham risk stratified by intended revascularization. The number of patients and the 5-Year Kaplan-Meier event rates for patients randomized to MED and REV in each of the subgroups are reported. The hazard ratio for MED versus REV (diamond) and its 95% confidence interval is plotted using a log scale. The vertical line represents a HR of 1 (no randomized treatment effect). The interaction p-value is a test of equality of the HR’s among the levels of the subgroup variable. The left panel shows results for patients randomized in the PCI stratum and the right shows results for patients in the CABG stratum.