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Volume 342:989-997 April 6, 2000 Number 14 Next

Abstract PDF Editorial by Haffner, S. M. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article PubMed Citation

ABSTRACT

Background Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients.

Methods We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models.

Results Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarction, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident.

Conclusions Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease.

The purpose of the current investigation was to elucidate the mechanism leading to different clinical courses among patients with diabetes according to the type of revascularization they underwent (i.e., CABG or PTCA). In this regard, two findings from previous studies have particular relevance. First, in previous randomized, controlled trials^4,5 CABG was associated with better outcomes in patients who had myocardial infarction than was medical therapy. Second, it is widely reported^{6,7,8,9,10,11} that the mortality rate after myocardial infarction is considerably higher among patients with diabetes than among those without diabetes. We evaluated whether there is a protective effect of previous CABG at the time of myocardial infarction in patients with diabetes, and if so, the degree to which this mechanism could explain the observed survival benefit associated with CABG (as compared with coronary angioplasty) in such patients in BARI.

Methods

Study Design

The design of BARI has been described previously.^12,13 Briefly, patients were eligible for the study if they had severely symptomatic and angiographically confirmed multivessel coronary artery disease requiring revascularization and were suitable candidates for either PTCA or CABG as the initial revascularization procedure. Of 4107 eligible patients recruited at 18 clinical centers in the United States and Canada, 1829 agreed to undergo random assignment to either CABG or PTCA; 2010 underwent revascularization on the basis of a recommendation by their physician, and data on these patients were entered into a registry; and 268 declined all follow-up. Both the patients in the randomized group and those in the registry group were followed according to the protocol. At the end of an average of 5.5 years of follow-up, vital status was known for 98 percent of patients.

Annual electrocardiograms were required for all patients who were followed, and an additional electrocardiogram 4 to 14 weeks after entry into the study was also required for the patients who underwent randomization. In addition, electrocardiograms were obtained in patients in whom myocardial infarction was suspected. Reading, interpretation, and coding of the electrocardiograms were conducted by the core electrocardiography laboratory at St. Louis University.

The analysis reported here is restricted to data on 3603 patients, from both the randomized trial and the registry, who underwent revascularization by either CABG or PTCA within three months after entry into the study. Patients were classified as either having diabetes or not having diabetes, according to whether or not they were receiving insulin or oral hypoglycemic medication for the treatment of diabetes at the time of entry into the study.

End Points

Death from all causes was the primary end point. The diagnosis of Q-wave myocardial infarction either was established according to the criteria of Chaitman et al.¹⁴ or was based on the classification of death as determined by an independent mortality and morbidity classification committee. Only myocardial infarctions that occurred during follow-up were considered. Q-wave myocardial infarctions were defined as "spontaneous" if the patient had not undergone a revascularization procedure within the previous seven days, and as "procedural" otherwise. This report focuses on spontaneous Q-wave myocardial infarctions, which were considered "silent" (asymptomatic) if diagnosed by a routine electrocardiogram obtained as part of the protocol and not accompanied by chest pain or elevated enzyme levels.

All initial and repeated revascularization procedures (CABG and PTCA) were documented for each patient over the course of the entire follow-up period. All patients who underwent CABG, whether as an initial or a repeated revascularization procedure, were regarded as subject to the protective effect of CABG. For analytic purposes, this status was conferred at the completion of the surgery. Thus, patients who initially underwent PTCA and later had bypass surgery were regarded as being subject to the protective effect of CABG only after the CABG procedure.

Statistical Analysis

We used chi-square tests and Student's t-test to compare base-line characteristics and Kaplan–Meier analysis¹⁵ to estimate the cumulative rates of CABG and spontaneous Q-wave myocardial infarction. For comparisons between the patients who underwent CABG and those who did not (i.e., those who underwent only PTCA), the estimates used were based on transient-state life tables¹⁶ to accommodate changes in status with respect to CABG over time. For patients who did not have a Q-wave myocardial infarction, mortality rates were estimated from the time of the initial revascularization procedure; otherwise, they were estimated from the time of the Q-wave myocardial infarction. Results regarding mortality were evaluated with the use of Cox models,¹⁷ which included CABG and myocardial infarction as time-dependent covariates¹⁸ and other base-line variables as fixed covariates. These models were used to estimate and assess the significance of the relative risks of death that describe the protective effect of CABG both in the patients who had spontaneous Q-wave myocardial infarction and in those who did not and to compare the protective effect of CABG formally in these two groups by testing for an interaction between CABG and Q-wave myocardial infarction. Separate estimates were obtained for patients with diabetes and those without diabetes.

Base-line covariates included in the Cox models were either factors known to be important predictors of death or factors that were disproportionately more common among the patients in this study with diabetes who underwent CABG and had a subsequent spontaneous Q-wave myocardial infarction. All P values are two-tailed.

Results

Table 1 shows the base-line characteristics according to CABG status at last contact for the 641 patients with diabetes and the 2962 without diabetes. Among the patients who underwent CABG, 71 percent had the surgery as their initial revascularization procedure. As described previously,² the patients with diabetes, regardless of whether they underwent CABG, were more likely to be female and black and were more likely to have a history of congestive heart failure, hypertension, renal dysfunction, and peripher-al vascular disease than the patients without diabetes. However, a comparison of those who underwent CABG and those who did not undergo CABG during the study revealed some differences: those who eventually underwent CABG were more likely than those who did not to have undergone randomization, to be male (in the case of patients without diabetes), to have a fair or poor quality of life (a trend among patients with diabetes), to have unstable angina (a trend among patients with diabetes), and to present with more extensive and diffuse coronary artery disease.

View this table: [in this window] [in a new window]   Table 1. Base-Line Characteristics of the Patients According to Final Status with Respect to Coronary-Artery Bypass Grafting.

 
Overall, 1512 of the 3603 patients underwent CABG as their initial revascularization procedure (42 percent), and an additional 442 of the remaining 2091 patients (i.e., those who underwent PTCA first) underwent CABG sometime during the first year of follow-up. Thereafter, the rate of crossover to CABG decreased to an average annual incidence of 2.8 percent. A somewhat larger proportion of the patients with diabetes than of the patients without diabetes initially underwent revascularization by CABG (45 percent vs. 41 percent, P=0.08), and among the patients who initially underwent revascularization by PTCA, 34 percent of those with diabetes as compared with 29 percent of those without diabetes underwent CABG within five years (relative risk of crossover to CABG among patients with diabetes, 1.25; P=0.04). At five years, 64 percent of the patients with diabetes and 58 percent of those without diabetes had undergone CABG (Figure 1A).

View larger version (14K): [in this window] [in a new window]   Figure 1. Rate of Coronary-Artery Bypass Grafting (CABG) and Incidence of Spontaneous Q-Wave Myocardial Infarction. Panel A shows Kaplan–Meier estimates of the cumulative rate of CABG, and Panel B shows the cumulative incidence of spontaneous Q-wave myocardial infarction, both according to diabetes status. Panel C shows transient-state life-table estimates of the cumulative incidence of spontaneous Q-wave myocardial infarction according to whether patients had undergone CABG at the time of the myocardial infarction. Patients who did not undergo CABG were treated only with percutaneous transluminal coronary angioplasty (PTCA).

 
The incidence of a first spontaneous Q-wave myocardial infarction during follow-up was 4.8 percent at five years, and such infarctions occurred at a constant rate throughout this period. Patients with diabetes were 1.9 times as likely as those without diabetes to have a spontaneous Q-wave myocardial infarc-tion (P<0.001) (Figure 1B).

The incidence of spontaneous Q-wave myocardial infarction was nearly identical among the patients who underwent CABG and those who did not (Figure 1C). This was also true when the comparison was restricted to the patients with diabetes (data not shown). One hundred seventy-six patients had a total of 186 spontaneous Q-wave myocardial infarctions, 94 of which occurred in those who had undergone CABG (in 73 cases the procedure had been performed less than three years earlier, and in 46 cases less than one year earlier). Among the spontaneous Q-wave myocardial infarctions, 86 (46 percent) were silent.

Mortality at five years was 8 percent for the 2962 patients without diabetes and 20 percent for the 641 patients with diabetes (P<0.001). The corresponding rates for the patients who underwent CABG were 7 percent and 18 percent, respectively; they were 8 and 25 percent for those who did not undergo CABG (Figure 2A). The mortality rate for the 3263 patients who did not have a Q-wave myocardial infarction (91 percent of the total) was slightly lower than the overall rate (Figure 2B). The estimated five-year mortality rate after spontaneous Q-wave myocardial infarction (Figure 2C) varied little according to CABG status among the patients without diabetes (27 percent for those who underwent CABG and 30 percent for those who did not); however, the protection conferred by CABG was dramatic among the patients with diabetes: mortality was 17 percent among the patients who had a spontaneous Q-wave myocardial infarction and had undergone CABG, as compared with 80 percent among those who had a spontaneous Q-wave myocardial infarction but had not undergone CABG. For the patients with a spontaneous Q-wave myocardial infarction, the 17 percent mortality rate among those with diabetes who underwent CABG was not significantly different from the rates among those without diabetes.

View larger version (19K): [in this window] [in a new window]   Figure 2. Mortality after the Initial Revascularization Procedure. Panel A shows transient-state life-table estimates of the cumulative mortality in all patients, and Panel B shows the cumulative mortality in patients without Q-wave myocardial infarction, both according to diabetes status and with respect to coronary-artery bypass grafting (CABG) at the time of death. Panel C shows Kaplan–Meier estimates of the cumulative mortality in patients with spontaneous Q-wave myocardial infarction according to diabetes status and CABG status (the numbers in parentheses refer to the 186 spontaneous Q-wave myocardial infarctions that occurred in 176 patients). Patients who did not undergo CABG were treated only with percutaneous transluminal coronary angioplasty.

 
To quantify the protection conferred by CABG in patients with spontaneous Q-wave myocardial infarction, as compared with the more moderate protection seen in patients who did not have spontaneous Q-wave myocardial infarction, we estimated the effect of CABG in terms of relative risks of death (Table 2) by means of a Cox regression model. These relative risks were used to compare mortality between specific groups of patients who underwent CABG and similar groups who did not. Adjustments were made for age (>65 years vs. 65 years), history with respect to congestive heart failure, history with respect to renal dysfunction, BARI study group (randomized group vs. registry group), and the presence or absence of significant disease of the proximal left anterior descending artery, all at base line.

View this table: [in this window] [in a new window]   Table 2. Protective Effect of CABG, as Determined by Adjusted Relative Risks of Death.

 
Among the patients with diabetes, CABG conferred a considerable degree of protection in those with a spontaneous Q-wave myocardial infarction (relative risk of death, 0.09; P<0.001) and a moderate degree of protection in those without a spontaneous Q-wave myocardial infarction (relative risk, 0.65; P=0.02) (Table 2). Thus, among the patients with diabetes, the protective role of CABG was approximately seven times as great after spontaneous Q-wave myocardial infarction as in the absence of spontaneous Q-wave myocardial infarction.

Among the patients without diabetes, the estimated protective effect of CABG was smaller and was not significant (Table 2). Moreover, the reduction in mortality among the patients with diabetes who had a spontaneous Q-wave myocardial infarction, as compared with those who did not, was significantly different from the corresponding reduction among the patients without diabetes (P=0.04) (Table 2).

Similar interactions were found when at least one internal-thoracic-artery graft was used, which occurred in 81 percent of the bypass procedures (single graft in 70 percent plus double graft in 11 percent). The protective effect of CABG involving this type of graft was consistently stronger than that of all types of CABG combined (i.e., the relative risk of death was lower), both among the patients with diabetes (relative risk of death after a spontaneous Q-wave myocardial infarction, 0.07; relative risk of death in the absence of a spontaneous Q-wave myocardial infarction, 0.54) and among those without diabetes (relative risk of death after a spontaneous Q-wave myocardial infarction, 0.49; relative risk of death in the absence of a spontaneous Q-wave myocardial infarction, 0.90). The long-term benefit associated with the use of internal-thoracic-artery grafts was not counteracted by higher rates of short-term complications, such as sternal-wound infections (data not shown). The relative survival advantage conferred by CABG among the patients with diabetes was very similar regardless of whether the spontaneous Q-wave myocardial infarction was silent or symptomatic.

Discussion

Our analysis identified two major ways in which CABG protected patients with diabetes. First, there was a strong protective effect of CABG with respect to survival for the relatively few patients with diabetes who had a spontaneous Q-wave myocardial infarction during follow-up. Second, CABG moderately reduced mortality among the majority of patients with diabetes who remained free of myocardial infarction during follow-up. Thus, the type of revascularization (CABG) and the presence of spontaneous Q-wave myocardial infarction interacted with one another in a manner that resulted in greater protection in patients with diabetes. Among the patients without diabetes the protective effect of CABG was substantially less (and was not significant), regardless of whether the patients had a myocardial infarction. In this study, we limited the definition of what constituted clinically diagnosed infarction to infarctions characterized by major Q waves, events that have previously been shown to be associated with particularly poor prognosis in patients with diabetes.¹⁹

In contrast to its protective effect with respect to survival, the type of revascularization had no influence on the incidence of Q-wave myocardial infarction during follow-up. This is similar to the results of earlier comparisons of CABG and medical treatment.^4,20

The use of single or double internal-thoracic-artery grafts enhanced the protective effects of CABG without increasing the incidence of sternal-wound infections, an adverse effect others have reported.²¹ Since internal-thoracic-artery grafts are more likely to remain patent than venous grafts,²² the increased protection conferred by internal-thoracic-artery grafts provides indirect evidence that the efficacy of CABG is due to improved perfusion supplied by the graft, which mitigates the potentially fatal effect of ischemia due to obstructed or reduced blood flow in patients with diabetes. Also, this improved patency is particularly characteristic of the first few years after CABG, precisely the period during which most of the spontaneous myocardial infarctions in this study occurred.

The unequal protection afforded by the two types of coronary revascularization among the patients with diabetes, particularly during an acute ischemic episode, may be due in part to the different degree of myocardial jeopardy (defined as the proportion of the myocardium jeopardized by stenosis of 50 percent or more) after PTCA as compared with CABG. In the subgroup of 270 patients who were randomly assigned to treatment and who underwent angiography one year after initial revascularization,²³ the amount of jeopardized myocardium decreased substantially in both treatment groups; however, the patients who underwent PTCA had considerably more jeopardized myocardium at one year than the patients who underwent CABG (mean degree of myocardial jeopardy at base line and one year: 59.4 percent and 25.5 percent, respectively, for the patients who underwent PTCA, and 60.8 percent and 14.1 percent for the patients who underwent CABG).

Since patients with diabetes typically have more extensive and progressive disease than patients without diabetes, including disease in distal vessels, focal dilation with PTCA leaves a greater proportion of the myocardium ischemic than does CABG. Indeed, among the subgroup of randomized patients in our study, the difference in the proportion of jeopardized myocardium at one year between the patients with diabetes who underwent CABG and those who did not was larger than that between the patients without diabetes who underwent CABG and those who did not (P=0.04). Other studies have shown that coronary collaterals are also less likely to form in patients with diabetes than in patients without diabetes.²⁴

Although a higher degree of myocardial jeopardy and reduced collateral formation would not affect the incidence of plaque rupture leading to the occurrence of coronary occlusion, they would affect the magnitude of ischemia after occlusion and hence contribute to the increased mortality rate among the patients with diabetes who did not undergo CABG, as compared with those who did, in our study. We cannot speculate about whether PTCA offers more protection than no revascularization in the event of spontaneous myocardial infarction but, rather, simply observe that PTCA offers less protection than does bypass surgery in patients with diabetes.

With the introduction of lytic and platelet-based therapy, outcomes in general after myocardial infarction have greatly improved in both patients with diabetes and those without.²⁵ However, since myocardial infarctions in our study were identified from routine electrocardiograms obtained at the time of clinical presentation or from death records, not all patients had the opportunity to be treated with these therapies. Specific data on the use of such treatments were not collected.

In the Diabetes and Insulin–Glucose Infusion in Acute Myocardial Infarction study, an infusion of insulin and glucose, followed by daily subcutaneous treatment with insulin, resulted in a 52 percent reduction in mortality within one year after myocardial infarction among patients with diabetes.^26,27 This beneficial effect was attributed to improved metabolic control in the presence of an extreme increase in the level of catecholamines in blood and ischemic myocardium that is associated with sudden ischemic episodes. In the absence of insulin, such a rise stimulates rapid turnover of free fatty acids.

Although spontaneous Q-wave myocardial infarctions were more frequent in our study among the patients with diabetes than in those without diabetes, such infarctions were relatively rare. Thus, the protective effect of CABG for a patient with a myocardial infarction explained only about 50 percent of the overall reduction in mortality attributable to the procedure. The remaining benefit of CABG among the patients with diabetes was demonstrated by a constant reduction in mortality throughout follow-up, perhaps a result of the reduction in the degree of chronic ischemia.

Our report lacks information about factors specific to diabetes. We know very little about the duration and the severity of diabetes in the patients in this study, and we do not know how well the disease was controlled and with what measures. The glycometabolic state at the time of infarction is an important predictor of long-term outcome in patients with diabetes who have had an acute myocardial infarction.²⁸ Future studies of ischemic heart disease in patients with diabetes should collect additional data that would allow assessment of pathophysiologic abnormalities and the methods by which they are corrected.

^* A complete list of the Bypass Angioplasty Revascularization Investigation investigators has been published (Circulation 1997;96:1761-9).

Source Information

From the Bypass Angioplasty Revascularization Investigation Coordinating Center, University of Pittsburgh, Pittsburgh (K.M.D., M.S.L., M.M.B., R.M.H., R.H.); the National Institutes of Health, Bethesda, Md. (G.S.); the Mayo Clinic Foundation, Rochester, Minn. (R.L.F.); and St. Louis University Health Sciences Center, St. Louis (B.R.C.).

Address reprint requests to Dr. Detre at the BARI Coordinating Center, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St., 127 Parran Hall, Pittsburgh, PA 15261, or at detre{at}edc.gsph.pitt.edu.

References

1. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996;335:217-225. [Erratum, N Engl J Med 1997;336:147.] [Free Full Text]
2. Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation. Circulation 1997;96:1761-1769. [Free Full Text]
3. King SB III, Kosinski AS, Guyton RA, Lembo NJ, Weintraub WS. Eight year mortality in the Emory Angioplasty vs. Surgery Trial (EAST). J Am Coll Cardiol (in press).
4. Peduzzi P, Detre K, Murphy ML, et al. Ten-year incidence of myocardial infarction and prognosis after infarction: Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery. Circulation 1991;83:747-755. [Free Full Text]
5. Alderman EL. Late benefit of coronary surgery on mortality from myocardial infarction. Circulation 1991;83:1087-1089. [Free Full Text]
6. Soler N, Burnett M, Pentecost BL, Fitzgerald M, Malins JM. Myocardial infarction in diabetics. QJM 1975;44:125-132. [Free Full Text]
7. Czyzk A, Krolewski AS, Szablowska S, Alot A, Kopczynski J. Clinical course of myocardial infarction among diabetic patients. Diabetes Care 1980;3:526-529. [Abstract]
8. Malmberg K, Rydén L. Myocardial infarction in patients with diabetes mellitus. Eur Heart J 1988;9:259-264. [Free Full Text]
9. Herlitz J, Malmberg K, Karlson BW, Rydén L, Hjalmarson Å. Mortality and morbidity during a five-year follow-up of diabetics with myocardial infarction. Acta Med Scand 1988;224:31-38. [Medline]
10. Karlson BW, Herlitz J, Hjalmarson A. Prognosis of acute myocardial infarction in diabetic and non-diabetic patients. Diabet Med 1993;10:449-454. [Medline]
11. Jacoby RM, Nesto RW. Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis. J Am Coll Cardiol 1992;20:736-744. [Abstract]
12. Protocol for the Bypass Angioplasty Revascularization Investigation. Circulation 1991:84:Suppl V:V-1–V-27.
13. Bourassa MG, Roubin GS, Detre KM, et al. Bypass Angioplasty Revascularization Investigation: patient screening, selection, and recruitment. Am J Cardiol 1995;75:3C-8C. [CrossRef][Medline]
14. Chaitman BR, Zhou SH, Tamesis B, et al. Methodology of serial ECG classification using an adaptation of the NOVACODE for Q wave myocardial infarction in the Bypass Angioplasty Revascularization Investigation (BARI). J Electrocardiol 1996;29:265-277. [CrossRef][Medline]
15. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
16. Mantel N, Byar DP. Evaluation of response-time data involving transient states: an illustration using heart-transplant data. J Am Stat Assoc 1974;69:81-6.
17. Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
18. Cox DR, Oakes D. Analysis of survival data. London: Chapman & Hall, 1984:112-39.
19. Singer DE, Moulton AW, Nathan DM. Diabetic myocardial infarction: interaction of diabetes with other preinfarction risk factors. Diabetes 1989;38:350-357. [Abstract]
20. Davis KB, Alderman EL, Kosinski AS, Passamani E, Kennedy JW. Early mortality of acute myocardial infarction in patients with and without prior coronary revascularization surgery: a Coronary Artery Surgery Study Registry study. Circulation 1992;85:2100-2109. [Free Full Text]
21. Loop FD, Lytle BW, Cosgrove DM, et al. J. Maxwell Chamberlain Memorial Paper: sternal wound complications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care. Ann Thorac Surg 1990;49:179-187. [Abstract]
22. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med 1986;314:1-6. [Abstract]
23. Whitlow PL, Dimas AP, Bashore TM, et al. Relationship of extent of revascularization with angina at one year in the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 1999;34:1750-1759. [Free Full Text]
24. Abaci A, Oguzhan A, Kahraman S, et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation 1999;99:2239-2242. [Free Full Text]
25. Mak KH, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. J Am Coll Cardiol 1997;30:171-179. [Abstract]
26. Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995;26:57-65. [Abstract]
27. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ 1997;314:1512-1515. [Free Full Text]
28. Malmberg K, Norhammar A, Wedel H, Rydén L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation 1999;99:2626-2632. [Free Full Text]

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• Mak, K.-H., Faxon, D. P. (2003). Clinical studies on coronary revascularization in patients with type 2 diabetes. Eur Heart J 24: 1087-1103 [Abstract] [Full Text]  
• Werner, G. S., Richartz, B. M., Heinke, S., Ferrari, M., Figulla, H. R. (2003). Impaired acute collateral recruitment as a possible mechanism for increased cardiac adverse events in patients with diabetes mellitus. Eur Heart J 24: 1134-1142 [Abstract] [Full Text]  
• Niefeld, M. R., Braunstein, J. B., Wu, A. W., Saudek, C. D., Weller, W. E., Anderson, G. F. (2003). Preventable Hospitalization Among Elderly Medicare Beneficiaries With Type 2 Diabetes. Diabetes Care 26: 1344-1349 [Abstract] [Full Text]  
• Charlson, M. E., Isom, O. W. (2003). Care after Coronary-Artery Bypass Surgery. NEJM 348: 1456-1463 [Full Text]  
• Sobel, B. E., Frye, R., Detre, K. M. (2003). Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease: Rationale for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. Circulation 107: 636-642 [Abstract] [Full Text]  
• Sundt, T. M. III, Gersh, B. J., Smith, H. C. (2003). Indications for Coronary Revascularization. Card Surg Adult 2: 541-559 [Full Text]  
• Laakso, M., Kuusisto, J. (2003). Diabetology for cardiologists. Eur Heart J Suppl 5: B5-B13 [Abstract]  
• Naik, M J, Abu-Omar, Y, Alvi, A, Wright, N, Henderson, A, Channon, K, Forfar, J C, Taggart, D P (2003). Total arterial revascularisation as a primary strategy for coronary artery bypass grafting. Postgrad. Med. J. 79: 43-48 [Abstract] [Full Text]  
• Schwartz, L., Kip, K. E., Frye, R. L., Alderman, E. L., Schaff, H. V., Detre, K. M. (2002). Coronary Bypass Graft Patency in Patients With Diabetes in the Bypass Angioplasty Revascularization Investigation (BARI). Circulation 106: 2652-2658 [Abstract] [Full Text]  
• Sedlis, S. P., Morrison, D. A., Lorin, J. D., Esposito, R., Sethi, G., Sacks, J., Henderson, W., Grover, F., Ramanathan, K. B., Weiman, D., Saucedo, J., Antakli, T., Paramesh, V., Pett, S., Vernon, S., Birjiniuk, V., Welt, F., Krucoff, M., Wolfe, W., Lucke, J. C., Mediratta, S., Booth, D., Murphy, E., Ward, H., Miller, L., Kiesz, S., Barbiere, C., Lewis, D., Investigators of the Department of Veterans Affair, (2002). Percutaneous coronary intervention versus coronary bypass graft surgery for diabetic patients with unstable angina and risk factors for adverse outcomes with bypass: outcome of diabetic patients in the AWESOME randomized trial and registry. J Am Coll Cardiol 40: 1555-1566 [Abstract] [Full Text]  
• Popma, J. J., Kuntz, R. E., Baim, D. S. (2002). A Decade of Improvement in the Clinical Outcomes of Percutaneous Coronary Intervention for Multivessel Coronary Artery Disease. Circulation 106: 1592-1594 [Full Text]  
• Szabo, Z., Hakanson, E., Svedjeholm, R. (2002). Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting. Ann. Thorac. Surg. 74: 712-719 [Abstract] [Full Text]  
• Schinkel, A. F.L., Elhendy, A., van Domburg, R. T., Bax, J. J., Vourvouri, E. C., Sozzi, F. B., Valkema, R., Roelandt, J. R.T.C., Poldermans, D. (2002). Prognostic Value of Dobutamine-Atropine Stress Myocardial Perfusion Imaging in Patients With Diabetes. Diabetes Care 25: 1637-1643 [Abstract] [Full Text]  
• Beckman, J. A., Creager, M. A., Libby, P. (2002). Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management. JAMA 287: 2570-2581 [Abstract] [Full Text]  
• Detre, K. M., Holubkov, R. (2002). Coronary Revascularization on Balance: Robert L. Frye Lecture. Mayo Clin Proc. 77: 72-82 [Abstract]  
• Giri, S., Shaw, L. J., Murthy, D. R., Travin, M. I., Miller, D. D., Hachamovitch, R., Borges-Neto, S., Berman, D. S., Waters, D. D., Heller, G. V. (2002). Impact of Diabetes on the Risk Stratification Using Stress Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Symptoms Suggestive of Coronary Artery Disease. Circulation 105: 32-40 [Abstract] [Full Text]  
• Mukamal, K. J., Nesto, R. W., Cohen, M. C., Muller, J. E., Maclure, M., Sherwood, J. B., Mittleman, M. A. (2001). Impact of Diabetes on Long-Term Survival After Acute Myocardial Infarction: Comparability of risk with prior myocardial infarction. Diabetes Care 24: 1422-1427 [Abstract] [Full Text]  
• Modest, G. A., Ray, K. K., Sheridan, P. J., Chan, K. H., Barr, D. A., Khakoo, A. Y., Rastegar, D. A., Hemingway, H., Crook, A. M., Timmis, A. D. (2001). Underuse of Coronary Revascularization Procedures. NEJM 345: 294-296 [Full Text]  
• King, S. B. III (2001). Coronary artery bypass graft or percutaneous coronary interventions in patients with diabetes: another nail in the coffin or "too close to call?". J Am Coll Cardiol 37: 1016-1018 [Full Text]  
• Sobel, B. E. (2001). Acceleration of Restenosis by Diabetes : Pathogenetic Implications. Circulation 103: 1185-1187 [Full Text]  
• Bardsley, J. K., Passaro, M. (2001). The Alphabet Soup of Diabetes Research Studies. Diabetes Spectr. 14: 44-48 [Abstract] [Full Text]  
• (2001). CABG Beats Angioplasty for Diabetics. Journal Watch Cardiology 2001: 2-2 [Full Text]  
• Wong, C.-K, White, H.D (2000). Dithering over the treatment of diabetics with acute myocardial infarction. Eur Heart J 21: 1907-1909  
• (2000). CABG Better Than Angioplasty for Diabetics. Journal Watch Cardiology 2000: 4-4 [Full Text]  
• Haffner, S. M. (2000). Coronary Heart Disease in Patients with Diabetes. NEJM 342: 1040-1042 [Full Text]