Original Article
A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease
N Engl J Med 2009; 360:2503-2515June 11, 2009
- 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.)
Media in This Article
Figure 1
Enrollment and Randomization.Figure 2
Rates of Survival and Freedom from Major Cardiovascular Events.Article Activity
- Article
Patients with type 2 diabetes mellitus have a higher risk of cardiovascular events and death than those without diabetes.1-4 Few large, randomized trials have addressed the question of the optimal treatment for patients with diabetes and angiographically defined stable ischemic heart disease. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was designed to test treatment strategies for patients with coronary artery disease and diabetes. Our goal was to address the effects of therapy on the rate of myocardial ischemia, a major cause of death in patients with diabetes, and of insulin resistance, the fundamental mechanism underlying diabetes with profound cardiovascular consequences.5,6
Among patients with diabetes, studies have indicated that increased insulin levels predict adverse outcomes7,8 and that control of hyperglycemia by reducing insulin resistance, rather than by providing insulin, might improve cardiovascular outcomes. This approach is tempered by data suggesting a limited benefit9 or possible harm10,11 associated with the use of newer insulin-sensitizing thiazolidinedione drugs and the failure of three recent trials to show reductions in cardiovascular events from intensifying glucose control beyond the current recommendations of the American Diabetes Association.12
Although the effectiveness of coronary revascularization in relieving angina is well established, its benefit in reducing the rates of subsequent myocardial infarction and death has been shown only in patients with high-risk profiles13,14 or acute coronary syndromes.15,16 Studies of coronary revascularization in patients with moderate17 or with mild or no symptoms have had conflicting results.18,19 However, such trials have not focused on patients with diabetes, who are at high risk with even mild symptoms of myocardial ischemia.
Thus, we evaluated two cardiac treatment strategies and two glycemic treatment strategies in patients who were receiving uniform glycemic control and intensive therapy for cardiac risk factors.20 Our 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. Our 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.
Methods
Study Population
From January 1, 2001, to March 31, 2005, patients were enrolled at 49 clinical sites in the United States, Canada, Brazil, Mexico, the Czech Republic, and Austria. Treatment continued until the 6-year visit or until the last annual visit before December 1, 2008. Patients who were still enrolled in the trial were contacted between September and November 2008; national database searches were conducted for patients with unknown vital status.
Eligibility criteria included a diagnosis of both type 2 diabetes and coronary artery disease. The diagnosis of type 2 diabetes was based on the need for treatment with insulin or oral hypoglycemic drugs or a confirmed elevated blood glucose level. The diagnosis of coronary artery disease was documented on angiography (≥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). 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.
Treatment Strategies
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%. A key feature of the trial was that 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 (Figure 1Figure 1
Enrollment and Randomization.).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.21 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.22 Patients were seen monthly for the first 6 months and every 3 months thereafter.
Evaluation of Outcomes
The primary end point was death from any cause, and the principal secondary end point was a composite of death, myocardial infarction, or stroke (major cardiovascular events). The definition of nonfatal myocardial infarction included spontaneous, silent, and procedure-related events. According to the study's protocol, 12-lead electrocardiography was performed at baseline, at 3 months, at 1 year, and annually thereafter, before and after each revascularization procedure, and at the time of suspected ischemic events. The diagnosis of spontaneous myocardial infarction was based on a doubling of cardiac biomarkers (creatine kinase MB or troponin) and evidence of ischemia on the basis of symptoms, electrocardiography, or imaging. Major cardiovascular events 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. Silent myocardial infarction was defined as a Q-wave change of two grades on routine electrocardiography, according to the Minnesota code (see the Supplementary Appendix, available with the full text of this article at NEJM.org). Myocardial infarction was classified by the Core Electrocardiography Laboratory; stroke and cause of death were adjudicated by an independent clinical events committee. Core laboratory staff and committee members were unaware of study-group assignments.
Study Design
The trial design and baseline characteristics of the patients have been described previously.21-25 The protocol was approved by the institutional review board at the University of Pittsburgh and at each participating site. All patients provided written informed consent. Investigators at 49 clinical sites collected data, which were analyzed at the University of Pittsburgh. An independent data and safety monitoring board approved the study protocol and monitored the safety of patients. The trial was sponsored by the National Institutes of Health, with additional support from industry. Industry sponsors did not have access to outcome data at any time during the trial and did not participate in data analyses or the preparation of the manuscript.
Statistical Analysis
We compared baseline characteristics, follow-up measures, and clinical outcomes on an intention-to-treat basis according to the randomized study-group assignment. Continuous variables were compared with Student's t-test or Wilcoxon nonparametric statistics and categorical variables with chi-square statistics. Cross-sectional follow-up data were presented at 3 years, since follow-up ranged from 3 to 6 years. We compared rates of death and major cardiovascular events using Kaplan–Meier survival curves and log-rank statistics with a two-sided alpha level of 0.05. Within strata defined by the intended method of revascularization, we compared end points in the revascularization group and the medical-therapy group using a log-rank test at a two-sided alpha level of 0.01.24 Cox proportional-hazards regression models that included study-group assignment, stratum, and assigned study group according to stratum interaction were used to determine whether the study-group effect was significantly modified by the intended method of revascularization. In addition, the statistical interactions between the cardiac study groups and the glycemic study groups for rates of death and major cardiovascular events were tested overall and within the PCI and CABG strata at a two-sided alpha level of 0.05. Follow-up data regarding the rate of death were censored at the time of the last contact with the patient, whereas data for the principal secondary end point were censored at the last study-clinic visit.
In 2005, the follow-up period was extended by 1.5 years to increase the average follow-up to 5.3 years because recruitment of patients took longer than planned and the original target of 2800 patients was not met. The extension was designed to provide a power of 88% to detect a 30% reduction in the rate of death (from 14.0% to 9.8%) and a power of 95% to detect a 25% reduction in the rate of major cardiovascular events (from 24.0% to 18.0%).
Results
Patients
All the patients underwent clinically indicated coronary angiography before randomization; most of them provided consent during screening before angiography but after meeting clinical eligibility requirements. Thus, the number of patients who were excluded for reasons unrelated to coronary anatomy is unavailable. Of the 4623 patients with type 2 diabetes who consented to screening, 2187 were ineligible for randomization; 68 eligible patients declined to participate, and the remaining 2368 patients underwent randomization.24
Baseline characteristics were well balanced among the study groups (Table 1 in the Supplementary Appendix). Myocardial ischemia was symptomatic in 82.1% of patients, and the mean duration of diabetes was 10.4 years. The average follow-up was 5.3 years, and 2194 patients (92.7%) completed the study as designed (Fig. 1 in the Supplementary Appendix).
Study Treatments
Coronary revascularization was performed within 6 months in 95.4% of patients in the revascularization group, as compared with 13.0% of patients in the medical-therapy group (Fig. 2 in the Supplementary Appendix). At 5 years, 42.1% of patients in the medical-therapy group (43.3% in the PCI stratum and 39.7% in the CABG stratum) had undergone clinically indicated revascularization. Nearly 90% of patients in both the insulin-sensitization group and the insulin-provision group were taking their assigned medications at 3 years, although 43.4% of patients in the insulin-sensitization group and 11.8% of those in the insulin-provision group received medications from the alternative drug class to obtain adequate glycemic control (Fig. 2 in the Supplementary Appendix).
Among 765 patients in the revascularization group who underwent PCI, procedures were attempted on a mean (±SD) of 1.5±0.8 lesions. Of these procedures, 20.7% involved a multivessel intervention; 34.7% of the patients received a drug-eluting stent, and 56.0% received a bare-metal stent; the other 9.3% did not receive a stent. After drug-eluting stents became available in April 2003, 61.0% of the initial PCI procedures involved the use of such stents. Of the 347 patients in the revascularization group who underwent CABG, 36.0% were treated off-pump, and 94.2% received an internal mammary-artery graft; a mean of 3.0±1.0 distal anastomoses were performed. The 30-day rate of death was 0.5% in the PCI subgroup and 1.4% in the CABG subgroup; the 30-day composite end point of death, myocardial infarction, or stroke occurred in 3.5% of the patients after PCI and in 4.6% after CABG.
At the 3-year follow-up, the most frequently used drugs in the insulin-provision group were insulin (60.7%) and sulfonylurea (52.0%); in the insulin-sensitization group, the most frequently used drugs were metformin (74.6%) and a thiazolidinedione (62.1%) (Table 1Table 1
Use of Medications, Risk Factors, and Adverse Events.). At 3 years, 5.6% of the patients were being treated for diabetes with diet alone. Throughout follow-up, the mean glycated hemoglobin levels were significantly lower in the insulin-sensitization group than in the insulin-provision group (P<0.001) (Table 1).All patients received intensive medical therapy during the trial in accordance with clinical guidelines, with common use of statins, aspirin, beta-blockers, and either angiotensin-converting–enzyme inhibitors or angiotensin-receptor blockers (Table 1). At 3 years, most patients had met treatment goals for levels of LDL cholesterol (82.6%) and blood pressure (71.1%). The body-mass index was significantly lower and levels of high-density-lipoprotein (HDL) cholesterol were significantly higher in the insulin-sensitization group than in the insulin-provision group during follow-up (Table 1).
Primary and Principal Secondary Outcomes
The rates of death from any cause did not differ significantly overall between the revascularization group and the medical-therapy group or between the insulin-sensitization group and the insulin-provision group (Figure 2Figure 2
Rates of Survival and Freedom from Major Cardiovascular Events.). The 5-year rate of survival was 88.3% among patients in the revascularization group, as compared with 87.8% among patients in the medical-therapy group (difference, 0.5%; 95% confidence interval [CI], −2.0 to 3.1; P=0.97 by the log-rank test). At 5 years, the rate of survival was 88.2% among patients in the insulin-sensitization group, as compared with 87.9% among patients in the insulin-provision group (difference, 0.3%; 95% CI, −2.2 to 2.9; P=0.89 by the log-rank test). The rate of freedom from major cardiovascular events did not differ significantly between the revascularization group and the medical-therapy group (difference, 1.3%; 95% CI, −2.2 to 4.9; P=0.70) or between the insulin-sensitization group and the insulin-provision group (difference, 2.4%; 95% CI, −1.2 to 6.0; P=0.13) (Figure 2).Revascularization Strata
The patients for whom CABG was prespecified as the intended method of revascularization had more extensive coronary disease,26 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 (Table 1 in the Supplementary Appendix).
The rate of death did not differ significantly between the revascularization group and the medical-therapy group in either the CABG or the PCI stratum (Figure 3Figure 3
Rates of Survival and Freedom from Major Cardiovascular Events, According to PCI and CABG Strata.). Patients in the CABG stratum who were assigned to the revascularization group had significantly fewer major cardiovascular events than did patients in the CABG stratum who were assigned to the medical-therapy group (P=0.01) (Figure 3). In contrast, rates of cardiovascular events among patients in the PCI stratum who were assigned to the revascularization group did not differ significantly from those who were assigned to the medical-therapy group (Figure 3). The interaction between study-group assignment and intended method of revascularization was statistically significant (P=0.002), which indicated that the benefit associated with prompt coronary revascularization, as compared with medical therapy, was significantly greater for patients selected for CABG than for patients selected for PCI. In the CABG stratum, nonfatal myocardial infarction occurred in markedly fewer patients in the revascularization group (7.4%) than in the medical-therapy group (14.6%) (Table 2 in the Supplementary Appendix).Evaluation of Treatment Combinations
An analysis of the rates of death and major cardiovascular events among the four mutually exclusive groups — revascularization plus insulin sensitization, revascularization plus insulin provision, medical therapy plus insulin sensitization, and medical therapy plus insulin provision — revealed no significant heterogeneity (P>0.05 for interaction) or treatment differences (P>0.05 for all four group comparisons by the log-rank test). When the analysis was stratified according to the intended method of revascularization, the rate of major cardiovascular events differed significantly among the four study groups in the CABG stratum (P=0.02), with the lowest rate seen in the group that underwent revascularization plus insulin sensitization; the interaction between the two treatments was of borderline significance (P=0.07) (Table 2Table 2
Kaplan–Meier Estimates for Event Rates at 5 Years.). The effect of revascularization on the rate of cardiovascular events was particularly evident among patients in the CABG stratum who were assigned to the insulin-sensitizing strategy, with a rate of 18.7% among patients in the revascularization group, as compared with 32.0% among those in the medical-therapy group (P=0.002).Adverse Events
Adverse event rates were infrequent and did not generally differ among the study groups (Table 2). However, severe hypoglycemia (which was defined as hypoglycemia requiring assistance with treatment and either a blood glucose level of <50 mg per deciliter [2.8 mmol per liter] or confusion, irrational or uncontrollable behavior, convulsions, or coma reversed by treatment that raises blood glucose levels) was more frequent among patients assigned to receive insulin provision (9.2%) than among those who received insulin sensitization (5.9%, P=0.003). Among patients with no history of heart failure, the rate of new congestive heart failure did not differ significantly between patients in the insulin-sensitization group (19.4%) and those in the insulin-provision group (16.6%, P=0.09). Peripheral pitting edema was more frequent in the insulin-sensitization group than in the insulin-provision group (P=0.02).
Discussion
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. Prompt revascularization significantly reduced major cardiovascular events, as compared with intensive medical therapy, among patients who were selected to undergo CABG but not among those who were selected to undergo PCI.
Our study was designed to compare coronary revascularization with intensive medical therapy, not to compare CABG with PCI. Patients who were selected to undergo CABG were expected to have higher event rates; indeed, among patients who were assigned to the medical-therapy group in the CABG stratum, the 5-year mortality (16.4%) was much higher than that among patients assigned to medical therapy in the PCI stratum (10.2%).
The study was designed to reflect how physicians might confront treatment decisions in practice. Our findings suggest that patients who have diabetes, evidence of myocardial ischemia, and extensive multivessel disease would benefit from prompt surgical revascularization mainly because of a lower rate of nonfatal myocardial infarction. However, for the many patients with type 2 diabetes who have less extensive coronary disease and for whom PCI is judged to be more appropriate, prompt revascularization did not reduce the risk of cardiovascular events, as compared with medical therapy. Approximately one third of patients in the PCI stratum who were assigned to undergo revascularization received a drug-eluting stent, but since these devices have not been shown to reduce rates of death or major cardiovascular events,27 their use probably did not affect the results.
It is important to note that all the patients who were assigned to receive medical therapy underwent careful clinical monitoring, and 42.1% had changes in the clinical course that called for later revascularization during 5 years of follow-up. In clinical practice, the initial treatment strategy for a patient with diabetes and coronary disease rarely remains constant over a 5-year period. The fact that most patients in the medical-therapy group did not require coronary revascularization during the 5-year period suggests that many patients may be safely treated with intensive medical therapy.
Our two-by-two factorial design allowed further comparisons between combinations of strategies. Among patients for whom CABG was selected as the intended method of revascularization, the combination of prompt revascularization and an insulin-sensitization strategy was associated with a significantly lower rate of major cardiovascular events than any of the other three treatment combination groups. Although previous studies have shown a beneficial effect on cardiovascular outcomes associated with the use of insulin sensitization with thiazolidinediones9,28,29 and metformin,30 our results cannot distinguish between the effect of either agent or the combination.
The strategies for glycemic control that we tested were not implemented at the time of initial diagnosis of diabetes, and there was inevitably less than complete differentiation of treatment regimens. The treatment regimens in our study reflect what is clinically possible for patients with established type 2 diabetes. Intensification of medical therapy and consistent monitoring led to improved control of cardiac risk factors across the board. Although only 28.4% of patients simultaneously achieved all three protocol targets at 3 years, the rates of control attained in this trial were much better than the rates recorded for community care31,32 and similar to those reported in other trials.33,34
The mean follow-up glycated hemoglobin values in the insulin-sensitization group and the insulin-provision group were close to the target level of 7.0% but differed significantly from each other. The mean difference of less than 0.5% in glycated hemoglobin levels between the two glycemic-control strategies in our study was less than the mean difference of 1.6% in the Veterans Affairs Diabetes Trial (VADT) (ClinicalTrials.gov number, NCT00032487),33 the difference of 1.1% in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (NCT00000620),35 and the difference of 0.6% in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (NCT00145925).34 Since none of these trials that compared different glycemic-control targets showed a significant reduction in cardiovascular events, it is unlikely that our results were due solely to differences in the level of glycemic control.
In our study, plasma insulin levels were consistently lower over time in patients in the insulin-sensitization group (median, 6.3 μU per milliliter) than in those in the insulin-provision group (median, 10.0 μU per milliliter), a finding that is consistent with the mechanisms of action of metformin and thiazolidinediones. Despite the need to administer insulin or sulfonylureas to some patients, patients in the insulin-sensitization group were maintained at or very near the target level for glycated hemoglobin. Moreover, the insulin-sensitization strategy was associated with fewer severe hypoglycemic episodes, less weight gain, and higher HDL levels than those in the insulin-provision strategy. These data may suggest that insulin sensitization is preferable for patients with type 2 diabetes and coronary disease.
Like all randomized clinical trials, our study was limited in terms of the generalizability of results to all patients with type 2 diabetes and coronary disease. Furthermore, confidence intervals for the overall between-group differences were within 3% for the rate of death and 6% for the rate of major cardiovascular events; smaller treatment effects could have been missed.
In summary, a strategy of prompt coronary revascularization in patients who had been treated with intensive medical therapy for diabetes and stable ischemic disease did not significantly reduce the rate of death from any cause or of major cardiovascular events. Insulin sensitization and insulin provision also had similar cardiovascular outcomes during a 5-year period. Among patients for whom CABG was deemed to be the appropriate treatment, prompt revascularization reduced the rate of major cardiovascular events, as compared with medical therapy, particularly among patients who were assigned to receive insulin sensitization. In the PCI stratum, however, revascularization did not reduce the rate of death or major cardiovascular events when added to medical therapy.
Supported by grants (U01-HL061744, U01-HL061746, U01-HL061748, and U01-HL063804) from the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases; and by GlaxoSmithKline, Lantheus Medical Imaging, Astellas Pharma, Merck, Abbott Laboratories, Pfizer, MediSense, Bayer, Becton Dickinson, J.R. Carlson Labs, Centocor, Eli Lilly, LipoScience, Novartis, and Novo Nordisk.
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.
The members of the writing group (Robert L. Frye, M.D., Mayo Clinic, Rochester, MN; Phyllis August, M.D., M.P.H., New York Hospital Queens, Queens, NY; Maria Mori Brooks, Ph.D., Regina M. Hardison, M.S., Sheryl F. Kelsey, Ph.D., Joan M. MacGregor, M.S., and Trevor J. Orchard, M.B., B.Ch., University of Pittsburgh, Pittsburgh; Bernard R. Chaitman, M.D., Saint Louis University, St. Louis; Saul M. Genuth, M.D., Case Western Reserve University, Cleveland; Suzanne H. Goldberg, R.N., M.S.N., National Heart, Lung, and Blood Institute, Bethesda, MD; Mark A. Hlatky, M.D., Stanford University, Palo Alto, CA; Teresa L.Z. Jones, M.D., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; Mark E. Molitch, M.D., Feinberg School of Medicine, Northwestern University, Chicago; Richard W. Nesto, M.D., Lahey Clinic Medical Center, Burlington, MA; Edward Y. Sako, M.D., Ph.D., University of Texas Health Science Center, San Antonio; and Burton E. Sobel, M.D., University of Vermont, Burlington) assume responsibility for the overall content and integrity of the article.
This article (10.1056/NEJMoa0805796) was published on June 7, 2009, at NEJM.org.
We dedicate this article to the memory of Katherine M. Detre, M.D., Dr.P.H., who initiated and led this study with a commitment to enhance the care of patients through the rigorous analysis of clinical evidence.
Source Information
Address reprint requests to Dr. Brooks at the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, 130 DeSoto St., Pittsburgh, PA 15261, or at mbrooks@pitt.edu.
Members of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group are listed in the Supplementary Appendix, available with the full text of this article at NEJM.org.
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- Citing Articles (166)
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Christian W. Hamm, Jean-Pierre Bassand, Stefan Agewall, Jeroen Bax, Eric Boersma, Hector Bueno, Pio Caso, Dariusz Dudek, Stephan Gielen, Kurt Huber, Magnus Ohman, Mark C. Petrie, Frank Sonntag, Miguel Sousa Uva, Robert F. Storey, William Wijns, Doron Zahger. (2012) Guía de práctica clínica de la ESC para el manejo del síndrome coronario agudo en pacientes sin elevación persistente del segmento ST. Revista Española de Cardiología 65:2, 173.e1-173.e55
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Albert Flotats. (2012) Myocardial perfusion imaging: a plus for coronary risk classification in diabetics. European Journal of Nuclear Medicine and Molecular Imaging
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(2012) Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial. Diabetologia 55:1, 36-45
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Madhu K. Natarajan, Bradley H. Strauss, Michael Rokoss, Christopher E. Buller, G.B. John Mancini, Changchun Xie, Tej N. Sheth, David Goodhart, Eric A. Cohen, Peter Seidelin, William Harper, Hertzel C. Gerstein. (2012) Randomized trial of insulin versus usual care in reducing restenosis after coronary intervention in patients with diabetes. the STent Restenosis And Metabolism (STREAM) study. Cardiovascular Revascularization Medicine
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Y. Sun, W. Ding, Q. Wei, W. C. Sheng. (2011) Disorder gene expression of extracellular matrix and adhesion molecules in saphenous vein conduits of diabetic patients. Interactive CardioVascular and Thoracic Surgery
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Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting. (2011) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. Journal of the American College of Cardiology 58:24, e44-e122
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George Hahalis, George Dangas, Periklis Davlouros, Dimitrios Alexopoulos. (2011) Revascularization strategies for stable multivessel and unprotected left main coronary artery disease: From BARI to SYNTAX. International Journal of Cardiology 153:2, 126-134
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, C. W. Hamm, J.-P. Bassand, S. Agewall, J. Bax, E. Boersma, H. Bueno, P. Caso, D. Dudek, S. Gielen, K. Huber, M. Ohman, M. C. Petrie, F. Sonntag, M. S. Uva, R. F. Storey, W. Wijns, D. Zahger, , J. J. Bax, A. Auricchio, H. Baumgartner, C. Ceconi, V. Dean, C. Deaton, R. Fagard, C. Funck-Brentano, D. Hasdai, A. Hoes, J. Knuuti, P. Kolh, T. McDonagh, C. Moulin, D. Poldermans, B. A. Popescu, Z. Reiner, U. Sechtem, P. A. Sirnes, A. Torbicki, A. Vahanian, S. Windecker, , S. Windecker, S. Achenbach, L. Badimon, M. Bertrand, H. E. Botker, J.-P. Collet, F. Crea, N. Danchin, E. Falk, J. Goudevenos, D. Gulba, R. Hambrecht, J. Herrmann, A. Kastrati, K. Kjeldsen, S. D. Kristensen, P. Lancellotti, J. Mehilli, B. Merkely, G. Montalescot, F.-J. Neumann, L. Neyses, J. Perk, M. Roffi, F. Romeo, M. Ruda, E. Swahn, M. Valgimigli, C. J. Vrints, P. Widimsky. (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal 32:23, 2999-3054
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David J. Maron, Gregg W. Stone, Daniel S. Berman, G. B. John Mancini, Theresa A. Scott, Daniel W. Byrne, Frank E. Harrell, Leslee J. Shaw, Rory Hachamovitch, William E. Boden, William S. Weintraub, John A. Spertus. (2011) Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists. American Heart Journal 162:6, 1034-1043.e13
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Jamieson M. Bourque, George A. Beller. (2011) Stress Myocardial Perfusion Imaging for Assessing Prognosis: An Update. JACC: Cardiovascular Imaging 4:12, 1305-1319
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Juan-Carlos Kaski, Antonio Arrebola-Moreno, Jason Dungu. (2011) Treatment strategies for chronic stable angina. Expert Opinion on Pharmacotherapy 12:18, 2833-2844
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Wouter G Wieringa, Gabija Pundziute, Tineke P Willems, Bart JGL de Smet. (2011) Clinical advances in imaging: how useful is computed tomography for guiding and evaluating cardiac interventions. Interventional Cardiology 3:6, 663-678
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L. David Hillis, Peter K. Smith, Jeffrey L. Anderson, John A. Bittl, Charles R. Bridges, John G. Byrne, Joaquin E. Cigarroa, Verdi J. DiSesa, Loren F. Hiratzka, Adolph M. Hutter, Michael E. Jessen, Ellen C. Keeley, Stephen J. Lahey, Richard A. Lange, Martin J. London, Michael J. Mack, Manesh R. Patel, John D. Puskas, Joseph F. Sabik, Ola Selnes, David M. Shahian, Jeffrey C. Trost, Michael D. Winniford. (2011) 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. Journal of the American College of Cardiology 58:24, e123-e210
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Michael J. Zellweger, Matthias E. Pfisterer. (2011) Therapeutic Strategies in Patients with Chronic Stable Coronary Artery Disease. Cardiovascular Therapeutics 29:6, e23-e30
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O. Gaemperli, A. Saraste, J. Knuuti. (2011) Cardiac hybrid imaging. European Journal of Echocardiography
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M. Roffi, D. J. Angiolillo, A. P. Kappetein. (2011) Current concepts on coronary revascularization in diabetic patients. European Heart Journal 32:22, 2748-2757
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Leslee J. Shaw, James K. Min, Rory Hachamovitch, Robert C. Hendel, Salvador Borges-Neto, Daniel S. Berman. (2011) Nomograms for estimating coronary artery disease prognosis with gated stress myocardial perfusion SPECT. Journal of Nuclear Cardiology
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Benjamin M. Scirica, Deepak L. Bhatt, Eugene Braunwald, Ph. Gabriel Steg, Jaime Davidson, Boaz Hirshberg, Peter Ohman, Deborah L. Price, Roland Chen, Jacob Udell, Itamar Raz. (2011) The design and rationale of the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus–Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 Study. American Heart Journal 162:5, 818-825.e6
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Davide Castagno, Jonathan Baird-Gunning, Pardeep S. Jhund, Giuseppe Biondi-Zoccai, Michael R. MacDonald, Mark C. Petrie, Fiorenzo Gaita, John J.V. McMurray. (2011) Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: Evidence from a 37,229 patient meta-analysis. American Heart Journal 162:5, 938-948.e2
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Robert A. Henderson, Adam D. Timmis. (2011) Almanac 2011: stable coronary artery disease. The national society journals present selected research that has driven recent advances in clinical cardiology. Revista Portuguesa de Cardiologia 30:11, 869-878
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Cornelis J. Roos, Roxana Djaberi, Joanne D. Schuijf, Eelco J. Koning, Ton J. Rabelink, Jan W. Smit, Alberto M. Pereira, Imad Younis, Bernies Hiel, Arthur J. Scholte, Jeroen J. Bax, J. Wouter Jukema. (2011) Relationship between vascular stiffness and stress myocardial perfusion imaging in asymptomatic patients with diabetes. European Journal of Nuclear Medicine and Molecular Imaging 38:11, 2050-2057
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Edward A. Cooper, J. James B. Edelman, Michael K. Wilson, Paul G. Bannon, Michael P. Vallely. (2011) Off-pump Coronary Artery Bypass Grafting in Elderly and High-risk Patients – A Review. Heart, Lung and Circulation 20:11, 694-703
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Robert A. Henderson, Adam D. Timmis. (2011) Almanac 2011: Stable coronary artery disease. The national society journals present selected research that has driven recent advances in clinical cardiology. Revista Portuguesa de Cardiologia (English Edition) 30:11, 869-878
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Jean-Louis Gayet, Franck Paganelli, Alain Cohen-Solal. (2011) Update on the medical treatment of stable angina. Archives of Cardiovascular Diseases 104:10, 536-544
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J C Kovacic, V Fuster. (2011) From Treating Complex Coronary Artery Disease to Promoting Cardiovascular Health: Therapeutic Transitions and Challenges, 2010–2020. Clinical Pharmacology & Therapeutics 90:4, 509-518
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A.A. Rivellese, P.M. Piatti. (2011) Consensus on: Screening and therapy of coronary heart disease in diabetic patients. Nutrition, Metabolism and Cardiovascular Diseases 21:10, 757-764
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Fadi G. Hage, Ami E. Iskandrian. (2011) Cardiovascular imaging in diabetes mellitus. Journal of Nuclear Cardiology 18:5, 959-965
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H. Reinhard, P. R. Hansen, F. Persson, L. Tarnow, N. Wiinberg, A. Kjaer, C. L. Petersen, K. Winther, H.-H. Parving, P. Rossing, P. K. Jacobsen. (2011) Elevated NT-proBNP and coronary calcium score in relation to coronary artery disease in asymptomatic type 2 diabetic patients with elevated urinary albumin excretion rate. Nephrology Dialysis Transplantation 26:10, 3242-3249
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O. Gaemperli, F. M. Bengel, P. A. Kaufmann. (2011) Cardiac hybrid imaging. European Heart Journal 32:17, 2100-2108
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Kevin L. Greason, Hartzell V. Schaff. (2011) Myocardial Revascularization by Coronary Arterial Bypass Graft: Past, Present, and Future. Current Problems in Cardiology 36:9, 325-368
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Savina Nodari, Alessandra Manerba, Alberto Vaccari, Giuseppe Milesi, Valentina Carubelli, Valentina Lazzarini, Carlo Lombardi, Federica Ettori, Marco Metra, Alessandra Dei Cas. (2011) Six-year prognosis of diabetic patients with coronary artery disease. European Journal of Clinical Investigationno-no
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Yuhua Liu, Chongren Tang. (2011) Regulation of ABCA1 functions by signaling pathways. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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Bernard R. Chaitman, Abhay A. Laddu. (2011) Stable angina pectoris: antianginal therapies and future directions. Nature Reviews Cardiology 9:1, 40-52
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P. Perrone-Filardi, S. Achenbach, S. Mohlenkamp, Z. Reiner, G. Sambuceti, J. D. Schuijf, E. Van der Wall, P. A. Kaufmann, J. Knuuti, S. Schroeder, M. J. Zellweger. (2011) Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology. European Heart Journal 32:16, 1986-1993
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Esther S.H. Kim, Thomas P. Carrigan, Venu Menon. (2011) International Participation in Cardiovascular Randomized Controlled Trials Sponsored by the National Heart, Lung, and Blood Institute. Journal of the American College of Cardiology 58:7, 671-676
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Prakash C. Deedwania, Enrique V. Carbajal. (2011) Medical Therapy Versus Myocardial Revascularization in Chronic Coronary Syndrome and Stable Angina. The American Journal of Medicine 124:8, 681-688
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Philip Joseph, Koon Teo. (2011) Optimal Medical Therapy, Lifestyle Intervention, and Secondary Prevention Strategies for Cardiovascular Event Reduction in Ischemic Heart Disease. Current Cardiology Reports 13:4, 287-295
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Yehuda Handelsman, Paul S. Jellinger. (2011) Overcoming Obstacles in Risk Factor Management in Type 2 Diabetes Mellitus. The Journal of Clinical Hypertension 13:8, 613-620
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Sheng-Chia Chung, Mark A. Hlatky, David Faxon, Kodangudi Ramanathan, Dale Adler, Arshag Mooradian, Charanjit Rihal, Roslyn A. Stone, Joyce T. Bromberger, Sheryl F. Kelsey, Maria Mori Brooks. (2011) The Effect of Age on Clinical Outcomes and Health Status. Journal of the American College of Cardiology 58:8, 810-819
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Leslee J. Shaw, Rory Hachamovitch, James Min, Daniel S. Berman. (2011) Importance of Residual Myocardial Ischemia After Intervention in the Genesis of Cardiovascular Events Among Patients with Chronic Coronary Artery Disease. Current Cardiology Reports 13:4, 280-286
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Sheng-Chia Chung, Mark A. Hlatky, Roslyn A. Stone, Jamal S. Rana, Jorge Escobedo, William J. Rogers, Joyce T. Bromberger, Sheryl F. Kelsey, Maria Mori Brooks. (2011) Body mass index and health status in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial (BARI 2D). American Heart Journal 162:1, 184-192.e3
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Rafael Ortega Basagoiti. (2011) Peregrinaje de un antidiabético hasta su aprobación por las agencias internacionales del medicamento. Situación actual. Avances en Diabetología 27:4, 107-114
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Hisato Takagi, Takuya Umemoto. (2011) Percutaneous coronary intervention versus medical therapy for stable coronary artery disease: Meta-regression analysis of mortality and morbidity against stent use. International Journal of Cardiology 150:1, 90-92
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Javier Sanz, George D. Dangas. (2011) Dynamic Nature of Coronary Plaques and Clinical Outcomes in Diabetic Patients: Is Change in Itself Bad?. Revista Española de Cardiología (English Edition) 64:7, 549-550
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Mark WI Webster. (2011) Clinical practice and implications of recent diabetes trials. Current Opinion in Cardiology 26:4, 288-293
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Javier Sanz, George D. Dangas. (2011) Naturaleza dinámica de las placas coronarias y resultados clínicos en pacientes diabéticos: ¿es malo el cambio de por sí?. Revista Española de Cardiología 64:7, 549-550
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Myriam Moret, Philippe Moulin. (2011) Dépistage de l’ischémie myocardique silencieuse des patients diabétiques : modalités et enjeux. La Presse Médicale 40:6, 625-633
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M. Noutsias, B. Maisch. (2011) Treatment of cardiovascular diseases in cancer patients. Herz 36:4, 340-345
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(2011) CardioPulse Articles * Women's heart health: the focus of this issue * Portrait of C. Noel Bairey Merz, MD, FACC, FAHA * The development of novel cardiovascular therapies for the future * Development of cardiology research in Japan * Personal experience of emigre cardiologist Cihan Cevik, MD, FESC * From the heart of Istanbul to the Texas Heart Institute * Portrait of National Cardiology and Society: Iceland * Cardiologists on this island in the North Atlantic between Europe and the USA, draw on the best from both cultures for their small population * People's corner: Awards * People's corner: In Memorium. European Heart Journal 32:11, 1301-1310
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Shigeo Horinaka. (2011) Use of Nicorandil in Cardiovascular Disease and Its Optimization. Drugs 71:9, 1105-1119
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C.A. Schneider. (2011) Medikamentös induzierte Hypoglykämie bei Typ-2-Diabetes-Patienten. Der Diabetologe 7:4, 259-261
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Linda G Mellbin, Klas Malmberg, Lars Rydén. (2011) Effects of glucose-lowering drugs in patients with diabetes and myocardial infarction. Diabetes Management 1:3, 281-289
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Alexander Kulik, William H. Shrank, Raisa Levin, Niteesh K. Choudhry. (2011) Adherence to Statin Therapy in Elderly Patients After Hospitalization for Coronary Revascularization. The American Journal of Cardiology 107:10, 1409-1414
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Emil M. deGoma, Daniel J. Rader. (2011) Novel HDL-directed pharmacotherapeutic strategies. Nature Reviews Cardiology 8:5, 266-277
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W. Motz, W. Kerner. (2011) Kardiale Endorganschäden bei Diabetes. Der Internist 52:5, 505-517
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Oliver Gaemperli, Philipp A. Kaufmann. (2011) Kardiale Hybridbildgebung. Clinical Research in Cardiology Supplements 6:S1, 32-42
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Arthur J. H. A. Scholte. (2011) Cardiac risk assessment in asymptomatic diabetes: Combing different imaging modalities and surrogate markers?. Journal of Nuclear Cardiology 18:3, 393-395
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Fernando Ovalle. (2011) Cardiovascular Implications of Antihyperglycemic Therapies for Type 2 Diabetes. Clinical Therapeutics 33:4, 393-407
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Thomas D Stuckey, Bruce R Brodie. (2011) Outcomes with drug-eluting stents in diabetic patients. Interventional Cardiology 3:2, 235-245
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Robert J. Richards, L. Yvonne Melendez-Ramirez, William T. Cefalu. 2011. Insulin Sensitizers Versus Secretagogues as First-Line Therapy for Diabetes: Rationale for Clinical Choice. , 71-78.
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Stephen H. Mckellar, Morgan L. Brown, Robert L. Frye. 2011. Is there an Optimal Revascularization Strategy in Diabetic Patients with Ischemic Heart Disease?. , 145-152.
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Edward L. Korn, Boris Freidlin. (2011) Inefficacy Interim Monitoring Procedures in Randomized Clinical Trials: The Need to Report. The American Journal of Bioethics 11:3, 2-10
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Claude Le Feuvre, Sophie Jacqueminet, Olivier Barthelemy. (2011) Myocardial ischemia: a silent epidemic in Type 2 diabetes patients. Future Cardiology 7:2, 183-190
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Sofiya Milman, Jill P. Crandall. (2011) Mechanisms of Vascular Complications in Prediabetes. Medical Clinics of North America 95:2, 309-325
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2011. Management of Inpatient Diabetes. , 47-63.
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Robert C. Hendel, Brian G. Abbott, Timothy M. Bateman, Ron Blankstein, Dennis A. Calnon, Jeffrey A. Leppo, Jamshid Maddahi, Matthew M. Schumaecker, Leslee J. Shaw, R. Parker Ward, David G. Wolinsky. (2011) The role of radionuclide myocardial perfusion imaging for asymptomatic individuals. Journal of Nuclear Cardiology 18:1, 3-15
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Victor Legrand, Scot Garg, Patrick Serruys, Kari Virtanen, Günter Szurawitzki, Vassilis Voudris, Alessandro Fontanelli, Knut Endersen, Igor Kranjec, Tessa Rademaker, Christodoulos Stefanidis, Kristel Wittebols. (2011) Influence of age on the clinical outcomes of coronary revascularisation for the treatment of patients with multivessel de novo coronary artery lesions: sirolimus-eluting stent vs. coronary artery bypass surgery and bare metal stent, insight from the multicentre randomised Arterial Revascularisation Therapy Study Part I (ARTS-I) and Part II (ARTS-II). EuroIntervention 6:7, 838-845
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H. C. Gerstein. (2011) Dysglycaemia, dyslipidaemia and hypertension: risk factors primarily focused on the disease or risk estimates primarily focused on the patient?. Diabetologia 54:2, 230-232
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Joel A. Lardizabal, Prakash C. Deedwania. (2011) The Anti-Ischemic and Anti-Anginal Properties of Statins. Current Atherosclerosis Reports 13:1, 43-50
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Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting, Alice K. Jacobs, Jeffrey L. Anderson, Nancy Albert, Mark A. Creager, Steven M. Ettinger, Robert A. Guyton, Jonathan L. Halperin, Judith S. Hochman, Frederick G. Kushner, E. Magnus Ohman, William Stevenson, Clyde W. Yancy. (2011) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. Catheterization and Cardiovascular Interventionsn/a-n/a
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Nico H.J. Pijls, Pim A.L. Tonino. (2011) Reply. Journal of the American College of Cardiology 57:1, 116
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Enrico Ammirati, Ornella E. Rimoldi, Paolo G. Camici. (2011) Is There Evidence Supporting Coronary Revascularization in Patients With Left Ventricular Systolic Dysfunction?. Circulation Journal 75:1, 3-10
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Masato Nakamura. (2011) Angiography Is the Gold Standard and Objective Evidence of Myocardial Ischemia Is Mandatory If Lesion Severity Is Questionable. Circulation Journal 75:1, 204-210
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Soichiro Kitamura. (2011) Physiological and Metabolic Effects of Grafts in Coronary Artery Bypass Surgery. Circulation Journal 75:4, 766-772
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Vicky Cheng, Sangeeta R. Kashyap. (2011) Weight Considerations in Pharmacotherapy for Type 2 Diabetes. Journal of Obesity 2011, 1-9
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Andrew J. Krentz. (2011) Rosiglitazone. Drugs 71:2, 123-130
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Hiroshi Ito. (2011) Optimal treatment for coronary artery disease in patients with diabetes: percutaneous coronary intervention, coronary artery bypass graft, and medications. General Thoracic and Cardiovascular Surgery 59:1, 6-13
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S. Jacqueminet, O. Barthelemy, F. Rouzet, R. Isnard, M. Halbron, A. Bouzamondo, D. Le Guludec, A. Grimaldi, J.-P. Metzger, C. Le Feuvre. (2010) A randomized study comparing isotope and echocardiography stress testing in the screening of silent myocardial ischaemia in type 2 diabetic patients. Diabetes & Metabolism 36:6, 463-469
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Yulan Zhao, Xuelian He, Chengjin Huang, Xiaonan Fu, Xuegui Shi, Ying Wu, Yijie Han, Naishi Li, Yanxiang Wu, Chew-Kiat Heng. (2010) The impacts of thiazolidinediones on circulating C-reactive protein levels in different diseases: A meta-analysis. Diabetes Research and Clinical Practice 90:3, 279-287
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Stefano Muzzarelli, Matthias Emil Pfisterer, Jan Müller-Brand, Michael Johannes Zellweger. (2010) Gate-keeper to coronary angiography: comparison of exercise testing, myocardial perfusion SPECT and individually tailored approach for risk stratification. The International Journal of Cardiovascular Imaging 26:8, 871-879
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Najwa Ouhoummane, Belkacem Abdous, Rabia Louchini, Louis Rochette, Paul Poirier. (2010) Trends in postacute myocardial infarction management and mortality in patients with diabetes. A population-based study from 1995 to 2001. Canadian Journal of Cardiology 26:10, 523-531
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Bernard R Chaitman, Mazen Hadid, Abhay A Laddu. (2010) Choice of initial medical therapy vs. prompt coronary revascularization in patients with type 2 diabetes and stable ischemic coronary disease with special emphasis on the BARI 2D trial results. Current Opinion in Cardiology 25:6, 597-602
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Elizabeth M. Holper, Tayo Addo. (2010) Clinical implications of the BARI 2D and COURAGE trials: the evolving role of percutaneous coronary intervention. Coronary Artery Disease 21:7, 397-401
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Giuseppe Tarantini, Davide Lanzellotti. (2010) Three-vessel coronary disease in diabetics: personalized versus evidence-based revascularization strategy. Future Cardiology 6:6, 797-809
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Maria Mori Brooks, William E. Boden, Robert L. Frye. (2010) Clinical implications of the BARI 2D and COURAGE trials: overview. Coronary Artery Disease 21:7, 383-385
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Daniel S. Menees, Eric R. Bates. (2010) Evaluation of patients with suspected coronary artery disease. Coronary Artery Disease 21:7, 386-390
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Lewis H. Kuller. (2010) Clinical implications of the BARI 2D and COURAGE trials of coronary artery disease. Coronary Artery Disease 21:7, 391-396
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