0
Clinical Review | Clinician's Corner

Diabetes and Coronary Revascularization FREE

James D. Flaherty, MD; Charles J. Davidson, MD
[+] Author Affiliations

Clinical Review Section Editor: Michael S. Lauer, MD. We encourage authors to submit papers for consideration as a “Clinical Review.” Please contact Michael S. Lauer, MD, at lauerm@ccf.org.

Author Affiliations: Northwestern Cardiovascular Institute, Feinberg School of Medicine, Northwestern University, Chicago, Ill.

More Author Information
JAMA. 2005;293(12):1501-1508. doi:10.1001/jama.293.12.1501.
Text Size: A A A
Published online

Context Patients with diabetes mellitus account for approximately 25% of the nearly 1.5 million coronary revascularization procedures performed each year in the United States and experience worse outcomes compared with nondiabetic patients.

Objectives To summarize the current state of evidence comparing the effectiveness and safety of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) in diabetic patients and to examine developments that may affect future outcomes in this high-risk group.

Evidence Acquisition Using the key terms diabetes mellitus, revascularization, coronary artery bypass, angioplasty, and coronary intervention, we searched MEDLINE from 1985 to 2004 for all randomized controlled trials (RCTs) comparing CABG surgery and PCI that reported outcomes in diabetic patients. Bibliographies and the Web sites of cardiology conferences were also reviewed. Studies comparing drug-eluting stents and bare-metal stents were identified in a similar fashion. The literature was reviewed to identify clinical measures that may impact revascularization outcomes in diabetic patients.

Evidence Synthesis We identified 6 RCTs comparing CABG surgery and PCI in a total of 950 diabetic patients. A mortality benefit for CABG over balloon-only PCI has been demonstrated in diabetic patients with multivessel coronary artery disease but has not been clearly established against stent-assisted PCI or in high-risk CABG patients. Use of glycoprotein IIb/IIIa receptor inhibitors has improved survival in diabetic patients undergoing PCI. Restenosis after PCI in diabetic patients has led to substantially higher repeat revascularization rates than after CABG. The use of drug-eluting stents has led to dramatic reductions in restenosis in diabetic patients. Ongoing RCTs comparing CABG and PCI using drug-eluting stents in diabetic patients will clarify the impact of these advances on outcomes.

Conclusions There is a relative lack of data from RCTs specifically comparing CABG surgery and PCI as currently practiced in diabetic patients. The mortality advantage and decreased rates of revascularization seen with CABG in subgroups from early trials may not be applicable in the era of drug-eluting stents, glycoprotein IIb/IIIa inhibitors, and the latest medical therapies.

Figures in this Article

Coronary artery disease (CAD) is virtually ubiquitous in adults with diabetes mellitus compared with nondiabetic patients and portends a worse prognosis.1 As the prevalence of diabetes mellitus increases worldwide, the challenges for the health care of these individuals are magnified. Although diabetic patients account for an increasing number of patients undergoing coronary artery revascularization, they experience worse outcomes than do nondiabetic patients undergoing either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The unique pathophysiology of atherosclerosis in patients with diabetes provides a framework for understanding their response to both medical therapy and revascularization. With this background, clinical outcomes potentially can be improved in this high-risk group.

The purpose of this review is to summarize the current state of evidence comparing the effectiveness and safety of CABG and PCI in diabetic patients. Evidence is also presented on specific factors that affect the outcomes of coronary revascularization in diabetic patients, including use of drug-eluting stents, glycoprotein (Gp) IIb/IIIa receptor inhibitors, and primary PCI.

We searched MEDLINE using the key terms diabetes mellitus, revascularization, coronary artery bypass, angioplasty, and coronary intervention. Reference lists of identified trials, review articles, and guidelines from official societies were reviewed. Web sites of cardiology conferences (including those of the American College of Cardiology [ACC], American Heart Association [AHA], and Transcatheter Cardiovascular Therapeutics) were searched for studies presented but not yet published. To compare CABG surgery with PCI we identified all studies that (1) were published between 1985 and 2004; (2) were randomized and controlled; (3) recruited patients known to have CAD in need of coronary revascularization; (4) separately reported data on diabetic patients; and (5) reported all-cause mortality at least 1 year postprocedure.

A similar search was performed to identify all randomized controlled trials (RCTs) comparing use of drug-eluting stents with bare-metal stents that reported outcomes for diabetic patients. MEDLINE searches were performed to identify studies, meta-analyses, and review articles that reported on outcomes in diabetic patients undergoing revascularization in specific situations (eg, acute myocardial infarction [MI]) or in patients with an identified medical or surgical cointervention (eg, Gp IIb/IIIa inhibitor use in PCI).

Scope of the Problem

Quiz Ref IDThere are more than 150 million adults worldwide estimated to have diabetes mellitus, and that number is expected to increase.2 Type 2 diabetes mellitus accounts for up to 95% of all cases.3 In 2001, the prevalence of diabetes in the United States was 8%, a relative increase of approximately 61% over a 10-year time span.4 Coronary heart disease is the most common cause of death in diabetic patients, at least half of whom die from cardiovascular causes.2 Diabetic patients are 2 to 4 times more likely to develop CAD than nondiabetic patients and to manifest this disease earlier in life.57 Individuals receiving medication for type 2 diabetes without known CAD have the same likelihood of experiencing an MI as those without diabetes but with a previous history of MI.6 Diabetic patients who have experienced an MI have a worse prognosis, particularly those treated with insulin.6,8

In addition to optimal medical therapy, a significant proportion of diabetic patients with CAD are candidates for revascularization. Nearly 1.5 million revascularization procedures, CABG surgery or PCI, are performed each year in the United States.9 Approximately 25% occur in diabetic patients, who fare worse after either type of revascularization compared with those without diabetes.1,911 There is increased perioperative morbidity and mortality as well as long-term mortality in diabetic patients undergoing CABG, particularly among those treated with insulin.1113 Diabetic patients undergoing PCI also have worse long-term survival and higher rates of repeat revascularization, primarily due to target-vessel restenosis.9

High-Risk Features of Diabetic Patients

Although patients with diabetes frequently have concurrent risk factors, diabetes itself is a powerful independent risk factor for cardiovascular events.1 There are several pathophysiologic features of atherosclerosis in diabetic patients that contribute to their worse prognosis and unique response to coronary revascularization. Metabolic and hematologic abnormalities associated with type 2 diabetes include hyperglycemia, insulin resistance, dyslipidemia, inflammation, and thrombophilia.14 Platelets express more Gp IIb/IIIa receptors and are more prone to aggregation, particularly in the presence of hyperglycemia.3 Together these abnormalities contribute to development of hypertension, endothelial cell dysfunction, accelerated atherogenesis and, eventually, coronary thrombosis. Diabetic nephropathy, including reduced creatinine clearance and proteinuria, identifies patients with markedly decreased survival after coronary revascularization.15

The anatomical patterns of CAD in diabetic patients may influence their prognosis and response to revascularization. Autopsy and angiographic studies have demonstrated that persons with diabetes more frequently have left main coronary artery lesions, multivessel disease, and diffuse CAD.1621 Diabetic patients have smaller luminal diameters in segments adjacent to obstructive coronary lesions and more completely occluded segments.8,19,22 In addition to a greater atherosclerotic burden, diabetic patients have a larger amount of lipid-rich plaques, which may be more prone to rupture.23 In an angioscopic study evaluating patients with unstable angina, those with diabetes had more fissured plaques and intracoronary thrombi.24 The coronary arteries of diabetic patients may be less able to adapt to significantly obstructive lesions. Diabetic patients have an impaired ability to develop coronary collaterals, which provide intrinsic bypass channels from one coronary segment or artery past an obstruction.25 Coronary arteries often undergo remodeling, which is an early compensatory enlargement at atherosclerotic sites to maintain luminal area and flow.26 However, intravascular ultrasound has shown that the coronary arteries of diabetic patients are less likely to undergo this favorable remodeling in response to atherosclerosis.27

Comparing CABG vs Balloon-Only PCI

There are no prospective RCTs that compare CABG surgery and PCI specifically in diabetic patients. However, there are several RCTs comparing these revascularization strategies that reported outcomes for subgroups of diabetic patients (Table 1). No trial included patients with significant (>50%) lesions in the left main coronary artery. Among the trials, the Bypass Angioplasty Revascularization Investigation (BARI) has received the most attention. This study compared CABG with balloon-only PCI as the initial treatment strategy in patients with multivessel CAD in need of revascularization.31,32 Overall, CABG and PCI yielded similar rates of in-hospital mortality (1.3% vs 1.1%, P<.01) and 5-year survival (89.3% vs 86.3%, P = .19), although those who underwent PCI required substantially more additional revascularization procedures.

Table Graphic Jump LocationTable 1. CABG Surgery vs PCI in Diabetic Patients: Subgroups From Randomized Controlled Trials

Among treated diabetic patients (n = 353) in the BARI trial there was a 15% absolute survival advantage for CABG (P = .003) at 5 years. However, this trial was conducted prior to the availability of coronary stents and intravenous platelet Gp IIb/IIIa inhibitors. Also, the trial did not designate aggressive postprocedural medical management now known to improve survival, such as the use of angiotension-converting enzyme inhibitors, β-blockers, antiplatelet therapy, and statins.

The Emory Angioplasty vs Surgery (EAST)29 and the Coronary Angioplasty vs Bypass Revascularization Investigation (CABRI)30 trials enrolled patients similar to those in the BARI trial. Subgroup analyses of diabetic patients showed that CABG tended to show better long-term survival over balloon-only PCI (Table 1). Perhaps due to inadequate sample size, this result did not reach statistical significance in either trial. In contrast, the Randomized Intervention Treatment of Angina (RITA-1) trial showed a trend toward more death in diabetic patients who underwent CABG vs balloon-only PCI.28 Of note, in this trial, 32% of diabetic patients had single-vessel CAD only.

Explaining the Mortality Benefit of CABG

There are several explanations for the apparent long-term superiority of CABG surgery over PCI in diabetic patients with multivessel CAD. Internal mammary artery (IMA) grafts provide better long-term patency than saphenous vein grafts and were used in 81% of the diabetic patients in the BARI trial. In fact, the survival advantage of CABG in diabetic patients was limited to those who received at least 1 IMA graft.36 The completeness of revascularization is another important factor. Diabetic patients in the BARI trial had a similar mean number of significant lesions in both the CABG and PCI groups (3.5 vs 3.4). However, while 87% of all intended vessels were successfully bypassed, only 76% of significant lesions were successfully treated with PCI.37

Bypass grafts may render future ischemic events to be less often fatal. An analysis of all BARI-eligible diabetic patients (n = 641) revealed that the likelihood of a spontaneous Q-wave MI was similar after PCI or CABG (about 8%-9%) in the first 5 years.12 However, the risk of death after a spontaneous Q-wave MI was substantially less in patients who underwent CABG (adjusted relative risk, 0.09; 95% confidence interval, 0.03-0.29; P<.001). Those who underwent CABG but did not experience a subsequent spontaneous Q-wave MI gained less protection from death (adjusted relative risk, 0.65; 95% confidence interval, 0.45-0.94; P = .02). The risk of death in each group was even lower when an IMA graft was used. Complete revascularization was achieved more frequently with CABG. These results suggest that CABG, particularly when an IMA graft was used, provided greater protection from death after ischemic events in diabetic patients studied in the BARI trial.

In a single-institution study, angiographic follow-up after PCI showed that diabetic patients are more likely to develop new coronary lesions compared with nondiabetic patients, particularly in instrumented vessels.38 Jeopardized myocardium is defined as the total territory of myocardium supplied by arteries with at least one 50% stenosis. The amount of jeopardized myocardium decreases initially following revascularization but subsequently increases due to restenosis, graft failure, or formation of new vessel lesions. In the BARI trial, diabetic patients had more jeopardized myocardium initially after PCI than after CABG, as well as at follow-up angiography.39 These results suggest that, in BARI trial participants with diabetes, CABG may provide better protection from vulnerable plaques compared with PCI.

Another single-institution angiographic study demonstrated that diabetic patients have higher rates of completely occlusive restenosis after PCI, a finding that independently correlated with increased long-term mortality.40 While diabetic patients in the BARI trial had markedly more restenosis after PCI, graft patency in those undergoing CABG surgery was not influenced by diabetic status.41 The long-term mortality advantage of CABG over PCI in diabetic patients therefore may in part be due to a more durable restoration of flow to the diseased arteries treated. The risk associated with repeat revascularization procedures due to restenosis after PCI may also negatively impact long-term survival.

As part of the BARI trial, eligible patients who elected not to undergo randomization were followed up in a registry. More diabetic patients chose PCI (n = 182) than CABG (n = 117). There was no significant mortality difference between those who received PCI or CABG at 5 years (14.4% vs 14.9%, P = .86).37 However, the patients with diabetes who underwent CABG had a higher prevalence of 3-vessel CAD and a greater number of significant lesions, including in the proximal left anterior descending artery. An analysis adjusted for worse clinical risk factors and angiographic profiles did not demonstrate an advantage for either strategy (relative risk of PCI, 1.24; 95% confidence interval, 0.71-2.18). These data from the BARI registry suggest that it may be reasonable to use the angiographic profile in diabetic patients to help select the type of revascularization.

Improving Outcomes in Diabetic Patients Undergoing PCI

Quiz Ref IDA potentially serious limitation of the aforementioned trials is that they were conducted in the era prior to widespread use of stents and Gp IIb/IIIa inhibitors. The use of coronary stents has reduced the incidence of abrupt vessel closure following balloon angioplasty and has decreased restenosis rates. The Arterial Revascularization Therapy Study (ARTS) compared multivessel coronary artery stenting with CABG surgery. In a subgroup of diabetic patients (n = 208) there was no statistically significant difference in mortality at 1 or 3 years between the 2 groups (Table 1).33,34 However, diabetic patients who underwent PCI required more repeat revascularization procedures. The greater need for CABG following PCI (10.0% vs 2.0%; P<.05) was attributed to a less complete revascularization (70.5% vs 84.1%; P<.001) achieved with stent-assisted PCI vs CABG.42 In the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) trial, patients at high surgical risk were randomized to receive PCI or CABG. In a subgroup of diabetic patients (n = 144), there was no statistically significant difference in survival throughout a 5-year follow-up period (Table 1).35 Stents (54%) and Gp IIb/IIIa inhibitors (11%) were permitted in the PCI group.

A pooled analysis from 3 trials (n = 1462) investigating the use of the Gp IIb/IIIa inhibitor abciximab with PCI in diabetic patients showed a 2% absolute mortality reduction (4.5% vs 2.5%, P = .03) at 1 year.43 Furthermore, diabetic patients in a meta-analysis from 6 studies (n = 6458) investigating various Gp IIb/IIIa inhibitors in acute coronary syndromes showed a 1.6% absolute mortality reduction (6.2% vs 4.6%, P = .007) at 30 days.44 This mortality benefit was greater in diabetic patients (n = 1279) who underwent PCI during the index hospitalization (4.0% vs 1.2%, P = .002).

In a recent study, diabetic patients undergoing planned PCI (n = 701), primarily with bare-metal stents, were pretreated with high-dose clopidogrel (600 mg) at least 2 hours before the procedure.45 Patients with recent acute coronary syndromes were excluded. The addition of abciximab to pretreatment clopidogrel did not lower the composite incidence of death or MI at 1 year (8.3% vs 8.6%, P = .91). This trial may have been underpowered to detect a significant difference. However, the use of abciximab did reduce the incidence of target-lesion revascularization (23.2% vs 30.4%, P = .03) at 1 year. The applicability of this effect with more frequent use of drug-eluting stents is unknown.

Quiz Ref IDRestenosis is the driving force behind the increased need for repeat revascularization in diabetic patients following PCI. Patients with diabetes exhibit increased intimal hyperplasia after PCI, which correlates with the degree of hyperglycemia. Diabetic patients with optimal glycemic control after PCI have rates of target vessel revascularization similar to those without diabetes.46 This suggests that medical therapy aimed at improved glycemic control might improve PCI outcomes. The thiazolidinediones, a newer class of insulin-sensitizing agents, have shown promise in reducing intimal hyperplasia and clinical restenosis rates in diabetic patients undergoing PCI with bare-metal stents.47 This effect may be independent of glycemic control.

Quiz Ref IDThe introduction of drug-eluting stents has further changed the landscape for PCI, with significant reductions in angiographic restenosis rates and need for repeat revascularization procedures. Drug-eluting stents implanted in diabetic patients have reduced restenosis rates in the target vessel with both rapamycin-eluting and paclitaxel-eluting stents (Table 2).4854 Rates of angiographic restenosis and need for target-lesion revascularization in diabetic patients are substantially lower than for nondiabetic patients receiving bare-metal stents. However, these rates are still higher in diabetic patients than in nondiabetic patients receiving drug-eluting stents. The potential impact of this reduction in restenosis on mortality, particularly in multivessel PCI, is unknown.

Table Graphic Jump LocationTable 2. Outcomes With Drug-Eluting US Bare-Metal Stents in Diabetic Patients
Primary PCI in Diabetic Patients

Patients with diabetes experiencing an acute MI with electrocardiographic evidence of ST-segment elevation present to the hospital later than patients without diabetes and are more likely to have congestive heart failure.8,16 Coronary artery bypass graft surgery in the setting of an ST-segment elevation MI is typically reserved for cases of failed PCI or for mechanical complications from the MI. Primary PCI may be preferred over thrombolytic therapy in diabetic patients presenting with an ST-segment elevation MI. In a pooled subset analysis from 11 RCTs of diabetic patients (n = 367) randomized to receive primary PCI or thrombolytic therapy, an invasive strategy led to a significant reduction in death or nonfatal MI at 30 days (9.2% vs 19.3%, P<.05).55 The relative benefit of primary PCI was greater in diabetic patients compared with nondiabetic patients. These data were reported before the availability of stents or Gp IIb/IIIa inhibitors.

In an observational study of diabetic patients, PCI performed with frequent stenting (94.2%) and use of Gp IIb/IIIa inhibitors (63.1%) was, compared with fibrinolysis, associated with lower 1-year rates of death or reinfarction (19.4% vs 36.4%, P = .007).56 In a nonrandomized group of diabetic patients undergoing primary PCI with stenting (n = 53), the use of abciximab was associated with lower mortality (0% vs 16.7%, P = .02) at 6 months, as well as reduced rates of reinfarction and repeat revascularization.57

Improving Outcomes in Diabetic Patients Undergoing CABG

Rigid glycemic control in diabetic patients undergoing CABG surgery improves outcomes. The use of a continuous insulin infusion has correlated with reduced perioperative mortality compared with subcutaneous insulin.58 A recent RCT compared continuous glucose-insulin-potassium (GIK) infusion to achieve a target serum glucose level of 125 to 200 mg/dL (6.9-11.1 mmol/L) against standard therapy (serum glucose <250 mg/dL [13.9 mmol/L]). Patients treated with GIK infusion developed fewer perioperative infections and atrial fibrillation and experienced shorter hospital stays.59 Over 2 years, patients treated with GIK infusion also had a significantly improved survival rate and fewer recurrent ischemic events.

Different surgical techniques have been investigated in diabetic patients. The use of multiple arterial conduits, including bilateral IMA grafts, appears to improve the long-term results of CABG. A recently published observational cohort showed improved 10-year survival and lower rates of recurrent MI and repeat CABG in diabetic patients with preserved left ventricular function who received bilateral IMA grafts.60 Additionally, there was no significant difference in the incidence of sternal wound infections, a concern that historically has limited the application of this approach. In recent years, there has been an increased use of “off-pump” CABG, ie, without cardiopulmonary bypass and cardiac arrest. An analysis of 346 diabetic patients who underwent off-pump CABG showed reduced complications but no survival advantage compared with nonrandomized controls who underwent on-pump CABG.61

Medical Management of Diabetic Patients

Quiz Ref IDAggressive cardiovascular risk factor modification is essential in the management of diabetic patients, including cigarette smoking cessation as well as control of blood pressure and cholesterol levels. Angiotensin-converting enzyme inhibitors have been shown to reduce cardiovascular events in diabetic patients, independent of their blood pressure–lowering effect.62 Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) reduce cardiovascular events in diabetic patients, irrespective of manifest CAD or a high baseline low-density lipoprotein cholesterol level.63,64 The use of antiplatelet agents significantly reduces vascular events in diabetic patients.65 The use of β-blockers in diabetic patients with CAD is associated with improved survival, even in those without a previous MI.66

A recent trial investigated the use of GIK infusion for 24 hours in patients with ST-segment elevation MI primarily treated with thrombolytic therapy.67 Survival at 30 days was not improved in diabetic patients treated with GIK infusion. In contrast, the use of a glucose-insulin infusion followed by an extended course of subcutaneous insulin has been shown to improve long-term survival in diabetic patients presenting with an acute MI.68 The long-term impact of intensive glycemic control on cardiovascular outcomes in all diabetic patients is less established.

Future Directions

Two important RCTs sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Heath are ongoing that compare PCI and CABG surgery in diabetic patients. The BARI 2 Diabetes (BARI 2D) trial is investigating 2600 diabetic patients with mild angina or documented myocardial ischemia and at least 1 significant (>50%) angiographic lesion.69 Using a 2 × 2 factorial design, patients are randomly assigned to 2 glucose management regimens—an insulin-sensitizing strategy vs an insulin-providing one, and medical therapy vs medical therapy with mechanical revascularization. The physician and the patient determine the type of revascularization: either PCI or CABG. The primary end point is 5-year mortality. This trial has a predefined medical treatment regimen and mandated guidelines, which include the use of statins, β-blockers, and angiotensin-converting enzyme inhibitors. Enrollment will be completed in March 2005.

Another National Heart, Lung, and Blood Institute–sponsored international prospective randomized trial, the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) study, will compare drug-eluting stents with adjunctive abciximab vs CABG in approximately 1500 diabetic patients with multivessel CAD. Enrollment for this trial will commence in 2005.

Recommendations

ACC/AHA task forces have issued separate guidelines for CABG surgery (latest update, 2004) and PCI (latest update, 2001).70,71 Treated diabetes is defined as a separate cohort within the PCI guidelines but is not specifically addressed in the CABG guidelines. According to the PCI guidelines, in all patients with a significant stenosis (>50%) of the left main coronary artery, CABG is preferred when feasible. CABG is also preferred to PCI in patients with moderate to severe symptoms and multivessel CAD in the setting of significant proximal left anterior descending artery involvement and treated diabetes. For single-vessel CAD or 2-vessel CAD not involving the proximal left anterior descending artery, there is no current consensus within the published guidelines.

Although the ACC/AHA guidelines provide a framework on which to base revascularization decisions, they are lacking in comparative recommendations for diabetic patients. Considering the most recent data involving diabetic patients, the algorithm shown in the Figure should be considered when choosing between CABG and PCI. Recommendations to improve outcomes in patients with diabetes undergoing CABG or PCI are listed in the Box.

Box. Strategies to Improve Outcomes in Diabetic Patients Undergoing Coronary Revascularization

CABG

  • If possible, use ≥1 arterial conduit, preferably an internal mammary artery, with preference given to anastomoses to the left anterior descending artery

  • Maintain rigid perioperative glycemic control (serum glucose <200 mg/dL [11.1 mmol/L]) with a continuous insulin infusion

PCI

  • Drug-eluting stents, with either rapamycin or paclitaxel, are strongly recommended

  • Glycoprotein IIb/IIIa inhibitors are strongly recommended, especially during an acute coronary syndrome

Abbreviations: CABG, coronary artery bypass graft surgery; PCI, percutaneous coronary intervention.

Figure. Selection of Elective Coronary Revascularization in Diabetic Patients
Graphic Jump Location

CABG indicates coronary artery bypass graft surgery; CAD, coronary artery disease; LAD, left anterior descending artery; PCI, percutaneous coronary intervention.
*Based on AWESOME criteria: medically refractory unstable angina plus 1 other high-risk feature (prior heart surgery, myocardial infarction within 7 days, left ventricular ejection fraction <35%, older than 70 years, or use of balloon pump.35).
†Based on the BARI trial and registry and the ARTS.3134,37 Also see Table 1.

Coronary revascularization has a prominent role in managing the heavy burden of CAD in the expanding population of diabetic patients. A host of unfavorable pathophysiologic and anatomical features of atherosclerosis in patients with diabetes has contributed to their worse prognosis and poorer response to revascularization. Several early studies comparing CABG surgery vs balloon-only PCI in subgroups of diabetic patients with multivessel CAD demonstrated a survival advantage and fewer repeat revascularization procedures with an initial surgical strategy. However, advances in medical therapy, PCI technology, and surgical techniques demand a continual reassessment of the treatment strategies for CAD available to diabetic patients. Ongoing clinical trials comparing coronary revascularization strategies specifically in diabetic patients will help define the optimal management strategy.

Corresponding Author: Charles J. Davidson, MD, 251 E Huron St, Feinberg Pavilion 8-526, Northwestern Memorial Hospital, Chicago, IL 60611 (cdavidso@nmh.org).

Author Contributions: Study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript: Davidson, Flaherty.

Critical revision of the manuscript for important intellectual content; administrative, technical, or material support; study supervision: Davidson.

Financial Disclosures: None reported.

Hammound T, Tanguay JF, Bourassa MG. Management of coronary artery disease: therapeutic options in patients with diabetes.  J Am Coll Cardiol. 2000;36:355-365
PubMed   |  Link to Article
Bonow RO, Gheorghiade M. The diabetes epidemic: a national and global crisis.  Am J Med. 2004;116:(suppl 5A)  2S-10S
PubMed   |  Link to Article
Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease pathophysiology, clinical consequences, and medical therapy: part I.  Circulation. 2003;108:1527-1532
PubMed   |  Link to Article
Mokdad AH, Ford ES, Bowman BA.  et al.  Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.  JAMA. 2003;289:76-79
PubMed   |  Link to Article
Lee CD, Folsom AR, Pankow JS, Brancati FL.Atherosclersosis Risk in Communities (ARIC) Study Investigators.  Cardiovascular events in diabetic and nondiabetic adults with or without history of myocardial infarction.  Circulation. 2004;109:855-860
PubMed   |  Link to Article
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.  N Engl J Med. 1998;339:229-234
PubMed   |  Link to Article
Sprafka JM, Burke GL, Folsom AR, McGovern PG, Hahn LP. Trends in prevalence of diabetes mellitus with myocardial infarction and effect of diabetes on survival: the Minnesota heart survey.  Diabetes Care. 1991;14:537-543
Link to Article
Woodfield SL, Lundergan CF, Reiner JS.  et al. GUSTO-I Angiographic Investigators.  Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-1 experience.  J Am Coll Cardiol. 1996;28:1661-1669
PubMed   |  Link to Article
Smith SC, Faxon D, Cascio W.  et al.  Diabetes and cardiovascular disease writing group VI: revascularization in diabetic patients.  Circulation. 2002;105:e165-e169
PubMed   |  Link to Article
Kugelmass AD, Cohen DJ, Houser F.  et al.  The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community: a report from the HCA database.  J Invasive Cardiol. 2003;15:568-574
Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery.  J Am Coll Cardiol. 2002;40:418-423
PubMed   |  Link to Article
Detre K, Lombardero MS, Brooks MM.  et al.  The effects of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction.  N Engl J Med. 2000;342:989-997
PubMed   |  Link to Article
Barsness GW, Peterson ED, Ohman EM.  et al.  Relationship between diabetes mellitus and long-term survival after coronary bypass and angioplasty.  Circulation. 1997;96:2551-2556
PubMed   |  Link to Article
Nesto RW. Correlation between cardiovascular disease and diabetes mellitus: current concepts.  Am J Med. 2004;116:(suppl 5A)  11S-22S
PubMed   |  Link to Article
Reeder GS, Holmes DR, Lennon RJ, Larson TS, Frye RL. Proteinuria, serum creatinine, and outcome of percutaneous coronary intervention in patients with diabetes mellitus.  Am J Cardiol. 2002;89:760-764
PubMed   |  Link to Article
Mak KH, Moliterno DJ, Granger CB.  et al. GUSTO-I Investigators.  Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction.  J Am Coll Cardiol. 1997;30:171-179
PubMed   |  Link to Article
Waller BF, Palumbo PJ, Lie JT, Roberts WC. Status of the coronary arteries at necropsy in diabetes mellitus with onset after age 30 years: analysis of 229 diabetic patients with and without clinical evidence of coronary heart disease and comparison to 183 control subjects.  Am J Med. 1980;69:498-506
PubMed   |  Link to Article
Lemp GF, Vander Zwaag R, Hughes JP.  et al.  Association between the severity of diabetes mellitus and coronary arterial atherosclerosis.  Am J Cardiol. 1987;60:1015-1019
PubMed   |  Link to Article
Ledru F, Ducimetiere P, Battaglia S.  et al.  New diagnostic criteria for diabetes and coronary artery disease: insights from an angiographic study.  J Am Coll Cardiol. 2001;37:1543-1550
PubMed   |  Link to Article
Burchfiel CM, Reed DM, Marcus EB, Strong JP, Hayashi T. Association of diabetes mellitus with coronary atherosclerosis and myocardial lesions: an autopsy study from the Honolulu Heart Program.  Am J Epidemiol. 1993;137:1328-1340
PubMed
Goraya TY, Leibson CL, Palumbo PJ.  et al.  Coronary atherosclerosis in diabetes mellitus: a population-based autopsy study.  J Am Coll Cardiol. 2002;40:946-953
PubMed   |  Link to Article
Mak KH, Faxon DP. Clinical studies on coronary revascularization in patients with type 2 diabetes.  Eur Heart J. 2003;24:1087-1103
PubMed   |  Link to Article
Moreno PR, Murcia AM, Palacios IF.  et al.  Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus.  Circulation. 2000;102:2180-2184
PubMed   |  Link to Article
Silva JA, Escobar A, Collins TJ, Ramee SR, White CJ. Unstable angina: a comparison of angioscopic findings between diabetic and nondiabetic patients.  Circulation. 1995;92:1731-1736
PubMed   |  Link to Article
Abaci A, Oguzhan A, Kahraman S.  et al.  Effect of diabetes mellitus on formation of coronary collateral vessels.  Circulation. 1999;99:2239-2242
PubMed   |  Link to Article
Hermiller JB, Tenaglia AN, Kisslo KB.  et al.  In vivo validation of compensatory enlargement of atherosclerotic coronary arteries.  Am J Cardiol. 1993;71:665-668
PubMed   |  Link to Article
Vavuranakis M, Stefanadis C, Toutouzas K, Pitsavos C, Spanos V, Toutouzas P. Impaired compensatory coronary artery enlargement in atherosclerosis contributes to the development of coronary artery stenosis in diabetic patients: an in vivo intravascular ultrasound study.  Eur Heart J. 1997;18:1090-1094
PubMed   |  Link to Article
Henderson RA, Pocock SJ, Sharp SJ.  et al. Randomised Intervention Treatment of Angina.  Long-term results of RITA-1 trial: clinical and cost comparisons of coronary angioplasty and coronary-artery bypass grafting.  Lancet. 1998;352:1419-1425
PubMed   |  Link to Article
King SB, Kosinski AS, Guyton RA, Lembo NJ, Weintraub WS.EAST Investigators.  Eight-year mortality in the Emory Angioplasty versus Surgery Trial (EAST).  J Am Coll Cardiol. 2000;35:1116-1121
PubMed   |  Link to Article
Kurbaan AS, Bowker TJ, Ilsley CD, Sigwart U, Richards AF.CABRI Investigators.  Difference in the mortality of the CABRI diabetic and nondiabetic populations and its relation to coronary artery disease and the revascularization mode.  Am J Cardiol. 2001;87:947-950
PubMed   |  Link to Article
Bypass Angioplasy Revascularization Investigation (BARI) Investigators.  Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease.  N Engl J Med. 1996;335:217-225
PubMed   |  Link to Article
Bypass Angioplasy Revascularization Investigation (BARI) Investigators.  Seven-year outcome in the Bypass Angioplasty Revascularization Investigation (BARI) by treatment and diabetic status.  J Am Coll Cardiol. 2000;35:1122-1129
PubMed   |  Link to Article
Abizaid A, Costa MA, Centemero M.  et al.  Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients: insights from the Arterial Revascularization Therapy Study (ARTS) trial.  Circulation. 2001;104:533-538
PubMed   |  Link to Article
Legrand VM, Serruys PW, Unger F.  et al.  Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease.  Circulation. 2004;109:1114-1120
PubMed   |  Link to Article
Sedlis SP, Morrison DA, Lorin JD.  et al.  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. 2002;40:1555-1566
PubMed   |  Link to Article
BARI Investigators.  Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease.  Circulation. 1997;96:1761-1769
PubMed   |  Link to Article
Detre KM, Guo P, Holubkov R.  et al.  Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Bypass Angioplasty Revascularization Investigation (BARI).  Circulation. 1999;99:633-640
PubMed   |  Link to Article
Rozenman Y, Sapozikov D, Mosseri M.  et al.  Long-term angiographic follow-up of coronary balloon angioplasty in patients with diabetes mellitus.  J Am Coll Cardiol. 1997;30:1420-1425
PubMed   |  Link to Article
Kip KE, Alderman EL, Bourassa MG.  et al.  Differential influence of diabetes mellitus on increased jeopardized myocardium after initial angioplasty or bypass surgery: Bypass Angioplasty Revascularization Investigation.  Circulation. 2002;105:1914-1920
PubMed   |  Link to Article
Van Belle E, Ketelers R, Bauters C.  et al.  Patency of percutaneous transluminal coronary angioplasty sites at 6-month angiographic follow-up: a key determinant of survival in diabetics after coronary balloon angioplasty.  Circulation. 2001;103:1218-1224
PubMed   |  Link to Article
Schwartz L, Kip KE, Frye RL, Alderman EL, Schaff HV, Detre KM. Coronary bypass graft patency in patients with diabetes in the Bypass Angioplasty Revascularization Investigation (BARI).  Circulation. 2002;106:2652-2658
PubMed   |  Link to Article
van den Brand MJ, Rensing BJ, Morel MA.  et al.  The effect of completeness of revascularization on event-free survival at one year in the ARTS trial.  J Am Coll Cardiol. 2002;39:559-564
PubMed   |  Link to Article
Bhatt DL, Marso SP, Lincoff M.  et al.  Abciximab reduces mortality in diabetics following percutaneous coronary intervention.  J Am Coll Cardiol. 2000;35:922-928
PubMed   |  Link to Article
Roffi M, Chew DP, Mukherjee D.  et al.  Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes.  Circulation. 2001;104:2767-2771
PubMed   |  Link to Article
Mehilli J, Kastrati A, Schuhlen H.  et al. ISAR-SWEET Investigators.  Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel.  Circulation. 2004;110:3627-3635
PubMed   |  Link to Article
Corpus RA, George PB, House JA.  et al.  Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention.  J Am Coll Cardiol. 2004;43:8-14
PubMed   |  Link to Article
Takagi T, Yamamuro A, Tamita K.  et al.  Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study.  Am Heart J. 2003;146:E5
PubMed   |  Link to Article
Moses JW, Leon MB, Popma JJ.  et al. SIRIUS Investigators.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.  N Engl J Med. 2003;349:1315-1323
PubMed   |  Link to Article
Holmes DR, Leon MB, Moses JW.  et al. SIRIUS Investigators.  Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis.  Circulation. 2004;109:634-640
PubMed   |  Link to Article
Moussa I, Leon MB, Baim DS. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients With de novo Coronary Artery Lesions) substudy.  Circulation. 2004;109:2273-2278
PubMed   |  Link to Article
Stone GW, Ellis SG, Cox DA.  et al. TAXUS-IV Investigators.  A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.  N Engl J Med. 2004;350:221-231
PubMed   |  Link to Article
Stone GW, Ellis SG, Cox DA.  et al. TAXUS-IV Investigators.  One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial.  Circulation. 2004;109:1942-1947
PubMed   |  Link to Article
Stone GW. The pivotal, prospective trial of the slow-rate release polymer-based paclitaxel-eluting taxus stent in patients with de novo coronary lesions: 2-year clinical results of the TAXUS-IV trial. Presented at: Transcatheter Cardiovascular Therapeutics (TCT); September 27-October 1, 2004; Washington, DC. Available at: http://www.tctmd.com. Accessed November 1, 2004
Sabaté M, Jimenez-Quevedo P, Angiolillo DJ.  et al. DIABETES Investigators.  Diabetes and sirolimus eluting stent trial: the DIABETES trial. Presented at Transcatheter Cardiovascular Therapeutics (TCT); September 27-October 1, 2004; Washington, DC. Available at: http://www.tctmd.com. Accessed November 1, 2004
Grines C, Patel A, Zijlstra F.  et al. PCAT Collaborators.  Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials.  Am Heart J. 2003;145:47-57
PubMed   |  Link to Article
Hsu LF, Mak KH, Lau KW.  et al.  Clinical outcomes of patients with diabetes mellitus and acute myocardial infarction treated with primary angioplasty or fibrinolysis.  Heart. 2002;88:260-265
PubMed   |  Link to Article
Montalescot G, Barragan P, Wittenberg O.  et al. ADMIRAL investigators.  Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.  N Engl J Med. 2001;344:1895-1903
PubMed   |  Link to Article
Furnary AP, Gao G, Grunkemeier GL.  et al.  Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.  J Thorac Cardiovasc Surg. 2003;125:1007-1021
PubMed   |  Link to Article
Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS. Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.  Circulation. 2004;109:1497-1502
PubMed   |  Link to Article
Endo M, Tomizawa Y, Nishida H. Bilateral versus unilateral internal mammary revascularization in patients with diabetes.  Circulation. 2003;108:1343-1349
PubMed   |  Link to Article
Magee MJ, Dewey TM, Acuff T.  et al.  Influence of diabetes on mortality and morbidity: off-pump coronary artery bypass grafting versus coronary artery bypass grafting with cardiopulmonary bypass.  Ann Thorac Surg. 2001;72:776-781
PubMed   |  Link to Article
Heart Outcomes Prevention Evaluation Study Investigators.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy.  Lancet. 2000;355:253-259
PubMed   |  Link to Article
Collins R, Armitage J, Parish S, Sleigh P, Peto R.HPS Collaborative Group.  MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5,963 people with diabetes: a randomized placebo-controlled trial.  Lancet. 2003;361:2005-2016
PubMed   |  Link to Article
Colhoun HM, Betteridge DJ, Durrington PN.  et al. CARDS Investigators.  Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial.  Lancet. 2004;364:685-696
PubMed   |  Link to Article
Antithrombotic Trialists’ Collaboration.  Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  BMJ. 2002;324:71-86
PubMed   |  Link to Article
Jonas M, Reicher-Reiss H, Boyko V.  et al. Bezafibrate Infarction Prevention (BIP) Study Group.  Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease.  Am J Cardiol. 1996;77:1273-1277
PubMed   |  Link to Article
Mehta SR, Yusuf S, Diaz R.  et al. CREATE-ECLA Trial Group Investigators.  Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial.  JAMA. 2005;293:437-446
PubMed   |  Link to Article
Malmberg K, Norhammar A, Wedel H, Ryden 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
PubMed   |  Link to Article
Sobel BE, Frye R, Detre KM. Burgeoning dilemmas in the management of diabetes and cardiovascular disease: rationale for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.  Circulation. 2003;107:636-642
PubMed   |  Link to Article
Eagle KA, Guyton RA, Davidoff R.  et al. American College of Cardiology/American Heart Association.  The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community: ACC/AHA guideline update for coronary artery bypass graft surgery: summary article.  J Am Coll Cardiol. 2004;44:1146-1154
PubMed   |  Link to Article
Smith SC Jr, Dove JT, Jacobs AK.  et al. American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty)/Society for Cardiac Angiography and Interventions.  ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines).  Circulation. 2001;103:3019-3041
PubMed   |  Link to Article

Figures

Figure. Selection of Elective Coronary Revascularization in Diabetic Patients
Graphic Jump Location

CABG indicates coronary artery bypass graft surgery; CAD, coronary artery disease; LAD, left anterior descending artery; PCI, percutaneous coronary intervention.
*Based on AWESOME criteria: medically refractory unstable angina plus 1 other high-risk feature (prior heart surgery, myocardial infarction within 7 days, left ventricular ejection fraction <35%, older than 70 years, or use of balloon pump.35).
†Based on the BARI trial and registry and the ARTS.3134,37 Also see Table 1.

Tables

Table Graphic Jump LocationTable 1. CABG Surgery vs PCI in Diabetic Patients: Subgroups From Randomized Controlled Trials
Table Graphic Jump LocationTable 2. Outcomes With Drug-Eluting US Bare-Metal Stents in Diabetic Patients

References

Hammound T, Tanguay JF, Bourassa MG. Management of coronary artery disease: therapeutic options in patients with diabetes.  J Am Coll Cardiol. 2000;36:355-365
PubMed   |  Link to Article
Bonow RO, Gheorghiade M. The diabetes epidemic: a national and global crisis.  Am J Med. 2004;116:(suppl 5A)  2S-10S
PubMed   |  Link to Article
Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease pathophysiology, clinical consequences, and medical therapy: part I.  Circulation. 2003;108:1527-1532
PubMed   |  Link to Article
Mokdad AH, Ford ES, Bowman BA.  et al.  Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.  JAMA. 2003;289:76-79
PubMed   |  Link to Article
Lee CD, Folsom AR, Pankow JS, Brancati FL.Atherosclersosis Risk in Communities (ARIC) Study Investigators.  Cardiovascular events in diabetic and nondiabetic adults with or without history of myocardial infarction.  Circulation. 2004;109:855-860
PubMed   |  Link to Article
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.  N Engl J Med. 1998;339:229-234
PubMed   |  Link to Article
Sprafka JM, Burke GL, Folsom AR, McGovern PG, Hahn LP. Trends in prevalence of diabetes mellitus with myocardial infarction and effect of diabetes on survival: the Minnesota heart survey.  Diabetes Care. 1991;14:537-543
Link to Article
Woodfield SL, Lundergan CF, Reiner JS.  et al. GUSTO-I Angiographic Investigators.  Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-1 experience.  J Am Coll Cardiol. 1996;28:1661-1669
PubMed   |  Link to Article
Smith SC, Faxon D, Cascio W.  et al.  Diabetes and cardiovascular disease writing group VI: revascularization in diabetic patients.  Circulation. 2002;105:e165-e169
PubMed   |  Link to Article
Kugelmass AD, Cohen DJ, Houser F.  et al.  The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community: a report from the HCA database.  J Invasive Cardiol. 2003;15:568-574
Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH. Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery.  J Am Coll Cardiol. 2002;40:418-423
PubMed   |  Link to Article
Detre K, Lombardero MS, Brooks MM.  et al.  The effects of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction.  N Engl J Med. 2000;342:989-997
PubMed   |  Link to Article
Barsness GW, Peterson ED, Ohman EM.  et al.  Relationship between diabetes mellitus and long-term survival after coronary bypass and angioplasty.  Circulation. 1997;96:2551-2556
PubMed   |  Link to Article
Nesto RW. Correlation between cardiovascular disease and diabetes mellitus: current concepts.  Am J Med. 2004;116:(suppl 5A)  11S-22S
PubMed   |  Link to Article
Reeder GS, Holmes DR, Lennon RJ, Larson TS, Frye RL. Proteinuria, serum creatinine, and outcome of percutaneous coronary intervention in patients with diabetes mellitus.  Am J Cardiol. 2002;89:760-764
PubMed   |  Link to Article
Mak KH, Moliterno DJ, Granger CB.  et al. GUSTO-I Investigators.  Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction.  J Am Coll Cardiol. 1997;30:171-179
PubMed   |  Link to Article
Waller BF, Palumbo PJ, Lie JT, Roberts WC. Status of the coronary arteries at necropsy in diabetes mellitus with onset after age 30 years: analysis of 229 diabetic patients with and without clinical evidence of coronary heart disease and comparison to 183 control subjects.  Am J Med. 1980;69:498-506
PubMed   |  Link to Article
Lemp GF, Vander Zwaag R, Hughes JP.  et al.  Association between the severity of diabetes mellitus and coronary arterial atherosclerosis.  Am J Cardiol. 1987;60:1015-1019
PubMed   |  Link to Article
Ledru F, Ducimetiere P, Battaglia S.  et al.  New diagnostic criteria for diabetes and coronary artery disease: insights from an angiographic study.  J Am Coll Cardiol. 2001;37:1543-1550
PubMed   |  Link to Article
Burchfiel CM, Reed DM, Marcus EB, Strong JP, Hayashi T. Association of diabetes mellitus with coronary atherosclerosis and myocardial lesions: an autopsy study from the Honolulu Heart Program.  Am J Epidemiol. 1993;137:1328-1340
PubMed
Goraya TY, Leibson CL, Palumbo PJ.  et al.  Coronary atherosclerosis in diabetes mellitus: a population-based autopsy study.  J Am Coll Cardiol. 2002;40:946-953
PubMed   |  Link to Article
Mak KH, Faxon DP. Clinical studies on coronary revascularization in patients with type 2 diabetes.  Eur Heart J. 2003;24:1087-1103
PubMed   |  Link to Article
Moreno PR, Murcia AM, Palacios IF.  et al.  Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus.  Circulation. 2000;102:2180-2184
PubMed   |  Link to Article
Silva JA, Escobar A, Collins TJ, Ramee SR, White CJ. Unstable angina: a comparison of angioscopic findings between diabetic and nondiabetic patients.  Circulation. 1995;92:1731-1736
PubMed   |  Link to Article
Abaci A, Oguzhan A, Kahraman S.  et al.  Effect of diabetes mellitus on formation of coronary collateral vessels.  Circulation. 1999;99:2239-2242
PubMed   |  Link to Article
Hermiller JB, Tenaglia AN, Kisslo KB.  et al.  In vivo validation of compensatory enlargement of atherosclerotic coronary arteries.  Am J Cardiol. 1993;71:665-668
PubMed   |  Link to Article
Vavuranakis M, Stefanadis C, Toutouzas K, Pitsavos C, Spanos V, Toutouzas P. Impaired compensatory coronary artery enlargement in atherosclerosis contributes to the development of coronary artery stenosis in diabetic patients: an in vivo intravascular ultrasound study.  Eur Heart J. 1997;18:1090-1094
PubMed   |  Link to Article
Henderson RA, Pocock SJ, Sharp SJ.  et al. Randomised Intervention Treatment of Angina.  Long-term results of RITA-1 trial: clinical and cost comparisons of coronary angioplasty and coronary-artery bypass grafting.  Lancet. 1998;352:1419-1425
PubMed   |  Link to Article
King SB, Kosinski AS, Guyton RA, Lembo NJ, Weintraub WS.EAST Investigators.  Eight-year mortality in the Emory Angioplasty versus Surgery Trial (EAST).  J Am Coll Cardiol. 2000;35:1116-1121
PubMed   |  Link to Article
Kurbaan AS, Bowker TJ, Ilsley CD, Sigwart U, Richards AF.CABRI Investigators.  Difference in the mortality of the CABRI diabetic and nondiabetic populations and its relation to coronary artery disease and the revascularization mode.  Am J Cardiol. 2001;87:947-950
PubMed   |  Link to Article
Bypass Angioplasy Revascularization Investigation (BARI) Investigators.  Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease.  N Engl J Med. 1996;335:217-225
PubMed   |  Link to Article
Bypass Angioplasy Revascularization Investigation (BARI) Investigators.  Seven-year outcome in the Bypass Angioplasty Revascularization Investigation (BARI) by treatment and diabetic status.  J Am Coll Cardiol. 2000;35:1122-1129
PubMed   |  Link to Article
Abizaid A, Costa MA, Centemero M.  et al.  Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients: insights from the Arterial Revascularization Therapy Study (ARTS) trial.  Circulation. 2001;104:533-538
PubMed   |  Link to Article
Legrand VM, Serruys PW, Unger F.  et al.  Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease.  Circulation. 2004;109:1114-1120
PubMed   |  Link to Article
Sedlis SP, Morrison DA, Lorin JD.  et al.  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. 2002;40:1555-1566
PubMed   |  Link to Article
BARI Investigators.  Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease.  Circulation. 1997;96:1761-1769
PubMed   |  Link to Article
Detre KM, Guo P, Holubkov R.  et al.  Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Bypass Angioplasty Revascularization Investigation (BARI).  Circulation. 1999;99:633-640
PubMed   |  Link to Article
Rozenman Y, Sapozikov D, Mosseri M.  et al.  Long-term angiographic follow-up of coronary balloon angioplasty in patients with diabetes mellitus.  J Am Coll Cardiol. 1997;30:1420-1425
PubMed   |  Link to Article
Kip KE, Alderman EL, Bourassa MG.  et al.  Differential influence of diabetes mellitus on increased jeopardized myocardium after initial angioplasty or bypass surgery: Bypass Angioplasty Revascularization Investigation.  Circulation. 2002;105:1914-1920
PubMed   |  Link to Article
Van Belle E, Ketelers R, Bauters C.  et al.  Patency of percutaneous transluminal coronary angioplasty sites at 6-month angiographic follow-up: a key determinant of survival in diabetics after coronary balloon angioplasty.  Circulation. 2001;103:1218-1224
PubMed   |  Link to Article
Schwartz L, Kip KE, Frye RL, Alderman EL, Schaff HV, Detre KM. Coronary bypass graft patency in patients with diabetes in the Bypass Angioplasty Revascularization Investigation (BARI).  Circulation. 2002;106:2652-2658
PubMed   |  Link to Article
van den Brand MJ, Rensing BJ, Morel MA.  et al.  The effect of completeness of revascularization on event-free survival at one year in the ARTS trial.  J Am Coll Cardiol. 2002;39:559-564
PubMed   |  Link to Article
Bhatt DL, Marso SP, Lincoff M.  et al.  Abciximab reduces mortality in diabetics following percutaneous coronary intervention.  J Am Coll Cardiol. 2000;35:922-928
PubMed   |  Link to Article
Roffi M, Chew DP, Mukherjee D.  et al.  Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes.  Circulation. 2001;104:2767-2771
PubMed   |  Link to Article
Mehilli J, Kastrati A, Schuhlen H.  et al. ISAR-SWEET Investigators.  Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel.  Circulation. 2004;110:3627-3635
PubMed   |  Link to Article
Corpus RA, George PB, House JA.  et al.  Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention.  J Am Coll Cardiol. 2004;43:8-14
PubMed   |  Link to Article
Takagi T, Yamamuro A, Tamita K.  et al.  Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study.  Am Heart J. 2003;146:E5
PubMed   |  Link to Article
Moses JW, Leon MB, Popma JJ.  et al. SIRIUS Investigators.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.  N Engl J Med. 2003;349:1315-1323
PubMed   |  Link to Article
Holmes DR, Leon MB, Moses JW.  et al. SIRIUS Investigators.  Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis.  Circulation. 2004;109:634-640
PubMed   |  Link to Article
Moussa I, Leon MB, Baim DS. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients With de novo Coronary Artery Lesions) substudy.  Circulation. 2004;109:2273-2278
PubMed   |  Link to Article
Stone GW, Ellis SG, Cox DA.  et al. TAXUS-IV Investigators.  A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.  N Engl J Med. 2004;350:221-231
PubMed   |  Link to Article
Stone GW, Ellis SG, Cox DA.  et al. TAXUS-IV Investigators.  One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial.  Circulation. 2004;109:1942-1947
PubMed   |  Link to Article
Stone GW. The pivotal, prospective trial of the slow-rate release polymer-based paclitaxel-eluting taxus stent in patients with de novo coronary lesions: 2-year clinical results of the TAXUS-IV trial. Presented at: Transcatheter Cardiovascular Therapeutics (TCT); September 27-October 1, 2004; Washington, DC. Available at: http://www.tctmd.com. Accessed November 1, 2004
Sabaté M, Jimenez-Quevedo P, Angiolillo DJ.  et al. DIABETES Investigators.  Diabetes and sirolimus eluting stent trial: the DIABETES trial. Presented at Transcatheter Cardiovascular Therapeutics (TCT); September 27-October 1, 2004; Washington, DC. Available at: http://www.tctmd.com. Accessed November 1, 2004
Grines C, Patel A, Zijlstra F.  et al. PCAT Collaborators.  Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials.  Am Heart J. 2003;145:47-57
PubMed   |  Link to Article
Hsu LF, Mak KH, Lau KW.  et al.  Clinical outcomes of patients with diabetes mellitus and acute myocardial infarction treated with primary angioplasty or fibrinolysis.  Heart. 2002;88:260-265
PubMed   |  Link to Article
Montalescot G, Barragan P, Wittenberg O.  et al. ADMIRAL investigators.  Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.  N Engl J Med. 2001;344:1895-1903
PubMed   |  Link to Article
Furnary AP, Gao G, Grunkemeier GL.  et al.  Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting.  J Thorac Cardiovasc Surg. 2003;125:1007-1021
PubMed   |  Link to Article
Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS. Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events.  Circulation. 2004;109:1497-1502
PubMed   |  Link to Article
Endo M, Tomizawa Y, Nishida H. Bilateral versus unilateral internal mammary revascularization in patients with diabetes.  Circulation. 2003;108:1343-1349
PubMed   |  Link to Article
Magee MJ, Dewey TM, Acuff T.  et al.  Influence of diabetes on mortality and morbidity: off-pump coronary artery bypass grafting versus coronary artery bypass grafting with cardiopulmonary bypass.  Ann Thorac Surg. 2001;72:776-781
PubMed   |  Link to Article
Heart Outcomes Prevention Evaluation Study Investigators.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy.  Lancet. 2000;355:253-259
PubMed   |  Link to Article
Collins R, Armitage J, Parish S, Sleigh P, Peto R.HPS Collaborative Group.  MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5,963 people with diabetes: a randomized placebo-controlled trial.  Lancet. 2003;361:2005-2016
PubMed   |  Link to Article
Colhoun HM, Betteridge DJ, Durrington PN.  et al. CARDS Investigators.  Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial.  Lancet. 2004;364:685-696
PubMed   |  Link to Article
Antithrombotic Trialists’ Collaboration.  Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  BMJ. 2002;324:71-86
PubMed   |  Link to Article
Jonas M, Reicher-Reiss H, Boyko V.  et al. Bezafibrate Infarction Prevention (BIP) Study Group.  Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease.  Am J Cardiol. 1996;77:1273-1277
PubMed   |  Link to Article
Mehta SR, Yusuf S, Diaz R.  et al. CREATE-ECLA Trial Group Investigators.  Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial.  JAMA. 2005;293:437-446
PubMed   |  Link to Article
Malmberg K, Norhammar A, Wedel H, Ryden 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
PubMed   |  Link to Article
Sobel BE, Frye R, Detre KM. Burgeoning dilemmas in the management of diabetes and cardiovascular disease: rationale for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.  Circulation. 2003;107:636-642
PubMed   |  Link to Article
Eagle KA, Guyton RA, Davidoff R.  et al. American College of Cardiology/American Heart Association.  The influence of diabetes mellitus on the practice and outcomes of percutaneous coronary intervention in the community: ACC/AHA guideline update for coronary artery bypass graft surgery: summary article.  J Am Coll Cardiol. 2004;44:1146-1154
PubMed   |  Link to Article
Smith SC Jr, Dove JT, Jacobs AK.  et al. American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty)/Society for Cardiac Angiography and Interventions.  ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines).  Circulation. 2001;103:3019-3041
PubMed   |  Link to Article
CME


You need to register in order to view this quiz.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 125

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles