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. 2011 Spring;16(1):16–22.

Coronary revascularization in diabetic patients: Current state of evidence

Mukesh Singh 1,✉, Rohit Arora 1, Vamsi Kodumuri 1, Sandeep Khosla 1, Evyan Jawad 1
PMCID: PMC3076161  PMID: 21523202

Abstract

Although diabetic patients constitute an increasing number of individuals undergoing percutaneous coronary intervention (PCI) and surgical revascularization, they experience worse outcomes than nondiabetic patients. The optimal coronary revascularization strategy in the diabetic population remains unclear in view of advancements in pharmacotherapy and technology of both PCI and surgical revascularization. Data to guide decision making are limited regarding the current choice between coronary artery bypass graft surgery and PCI using drug-eluting stents and newer antiplatelet agents in diabetic patients with multivessel coronary artery disease. The present article summarizes the current state of evidence for coronary revascularization in the diabetic population.

Keywords: CABG, Coronary revascularization, Diabetes mellitus, PCI

Diabetic patients have a greater burden of atherogenic risk factors than nondiabetic patients, including hypertension, obesity, dyslipidemia, insulin resistance and elevated levels of plasma fibrinogen (1–3). Many of these risk factors are also present in the prediabetic state before development of overt type 2 diabetes (4). Moreover, diabetes itself is a powerful independent risk factor for cardiovascular events (1). The National Cholesterol Education Program report from the United States and guidelines from Europe consider type 2 diabetes to be a coronary artery disease (CAD) equivalent, placing it in the highest risk category for CAD (5,6).

The prevalence of diabetes mellitus continues to increase worldwide (7–11). Due to advances in the management of diabetes and its complications, especially renal failure and infection, there has been a marked relative increase in morbidity and mortality from cardiovascular disease. Overall, cardiovascular disease, which includes CAD and cerebrovascular disease, accounts for 65% of all deaths among diabetic patients. Although much of these data are based on findings in patients with type 2 diabetes, patients with type 1 diabetes have similarly high morbidity and mortality rates (12,13). Patients with diabetes have a four- to sixfold increased risk for cardiovascular events compared with nondiabetic patients and appear to develop more severe CAD, with a greater tendency toward adverse events. The RR of myocardial infarction (MI) is 50% greater in diabetic men and 150% greater in diabetic women (14). A recent meta-analysis (15) estimated the risk of death from CAD to be 2.58 in diabetic men and 1.85 in diabetic women.

Despite significant improvements in CAD mortality rates, CAD remains the leading cause of death in the United States (16–21). With the aging population and an increasing prevalence of both diabetes and CAD, the number of interventional coronary and peripheral arterial procedures has markedly increased (22). Morbidity and mortality related to CAD present a great challenge in patients with diabetes mellitus. Revascularization of CAD is an important therapeutic intervention owing to its impact on both symptoms and prognosis. In the past decade, advancements in both percutaneous coronary intervention (PCI) and surgical techniques have continued to improve methods of coronary revascularization. Although there is evidence to suggest that these advancements have improved outcomes in diabetic patients, this population still experiences significantly worse outcomes compared with the general population (23), and the optimal revascularization strategy in diabetic patients remains unclear. The present article summarizes the current state of evidence regarding coronary artery revascularization in patients with diabetes mellitus.

ADVERSE OUTCOMES OF CORONARY REVASCULARIZATION IN DIABETES MELLITUS

Diabetic patients currently comprise approximately one-quarter of patients referred for PCI (24–26). Diabetic patients experience worse outcomes than nondiabetic patients undergoing either coronary artery bypass grafting (CABG) or PCI. There are several pathophysiological features of atherosclerosis (Table 1) in diabetic patients that contribute to their poorer prognosis and unique response to coronary revascularization (27).

TABLE 1.

Pathophysiological features of atherosclerosis in diabetes conferring high risk

Metabolic abnormalities
  Hyperinsulinemia and insulin resistance
  Hyperglycemia
  Increased prevalence of small, dense, low-density lipoprotein and triglyceride-rich lipoproteins
  Increased advanced glycation end product formation
  Increased oxidative stress and enhanced lipoprotein susceptibility to oxidation
Endothelial dysfunction
Hematological abnormalities
  Abnormal platelet function
  Abnormal coagulation system
    Increased plasma fibrinogen
  Impaired fibrinolytic system
    Increased plasminogen activator inhibitor-1
Impaired ability to form collaterals
Higher prevalence of obesity, hypertension and dyslipidemia
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When matched for other patient characteristics, diabetic patients have more extensive and diffuse CAD (26,28). Data from large populations of diabetic patients in the National Heart, Lung, and Blood Institute Dynamic Registry (26,29) showed that despite comparable acute procedural results, diabetic patients have lower long-term survival rates, and increased rates of reinfarction and target lesion revascularization compared with nondiabetic patients. Kip et al (26), in the National Heart, Lung, and Blood Institute Dynamic Registry, documented a doubling of diabetic mortality at nine years (35.9% versus 17.9%), with a mortality rate of more than 50% for diabetic patients with triple-vessel disease compared with nondiabetic patients (51.3% versus 25.1%). Similar results were reported by Schomig et al (4) in a retrospective review of more than 20,000 patients undergoing PCI from 1980 to 1999. During this period, in-hospital mortality in diabetic patients undergoing PCI nearly doubled in both the elective (0.8% versus 1.4%; P<0.001) and emergent (6.9% versus 12.7%; P<0.001) settings.

Diabetes is an independent risk factor for increased early and late mortality in patients treated with CABG (30–32). In a review of 9920 patients with diabetes and 2278 patients without diabetes from a single centre over 15 years, Calafiore et al (32) revealed lower survival rates in diabetic patients versus nondiabetic patients at five-year (78% versus 88%) and 10-year (50% versus 71%) follow-up. In addition to decreased survival, patients with diabetes have been shown to have increased rates of sternal wound infection (33–35), mediastinitis (36) and saphenous vein harvest site infections (37). Diabetes has also been associated with increased rates of neurological and renal complications, leading to prolonged postoperative intensive care unit stays (38). The RR of renal dysfunction in diabetic patients is fivefold greater than in nondiabetic patients during cardiac surgery (39). Diabetes increases the risk of stroke (39–41) and renal failure with CABG and valve surgery (42,43). Postoperative myocardial dysfunction appears to be exacerbated by diabetes because it is an independent predictor of postoperative low cardiac output syndrome (44). There is evidence to suggest that diabetic patients are at high risk for readmission following CABG (45). Thus, diabetic patients represent a challenging patient population with severe, multivessel CAD, often necessitating surgical revascularization, which is associated with high morbidity and mortality rates.

PRIMARY PCI IN DIABETIC PATIENTS WITH ST ELEVATION MI

Diabetic patients with acute ST elevation MI (STEMI) who present later to the hospital are more likely to experience congestive heart failure and have longer door-to-balloon times than nondiabetic patients (46). Primary PCI has been shown to improve survival, and reduce the risk of recurrent MI, stroke and intracranial hemorrhage compared with systemic thrombolysis in patients with acute STEMI – especially those with diabetes mellitus (47,48). A subset analysis of clinical trials (48,49) comparing primary PCI with thrombolysis in diabetic patients showed a significant reduction in death or MI at 30 days (9.2% versus 19.3%; P<0.05) (48), a higher infarct-related artery patency rate (88% versus 31%; P<0.001), and improved left ventricular function (left ventricular ejection fraction 49% versus 36%; P<0.05) and long-term survival (49).

The Abciximab Before Direct Angioplasty and Stenting in Myocardial Infarction (ADMIRAL) trial (50) showed a significant reduction in death (0% versus 16.7%; P=0.02) as well as the combined end point of death, reinfarction or revascularization (20.7% versus 50.0%, P=0.02) at six months in diabetic patients when glycoprotein IIb/IIIa inhibitors were added to their antiplatelet regimen. Montalescot et al (51), in an individual patient data meta-analysis of diabetic patients with STEMI, reported improved survival at three years in patients treated with abciximab (22% versus 40%, P=0.02). The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial (52), assessing the benefit of adjunctive therapy with abciximab in diabetic patients, did not show any benefit in terms of survival or recurrent MI, although the risk of repeat revascularization procedures was significantly improved. CABG in the setting of acute STEMI remains reserved for patients with mechanical complications (papillary muscle dysfunction or rupture of the interventricular septum) and for rare cases of failed PCI.

PCI VERSUS CABG

Since the early days of PCI, CABG has been accepted as the preferred method of revascularization for multivessel disease over angioplasty. These studies compared PCI using percutaneous transluminal coronary angioplasty (PTCA) with or without stenting versus CABG in patients with diabetes. The current guidelines (53) for revascularization of a diabetic patient with multivessel CAD favour CABG, reflecting the observations from the Bypass Angioplasty Revascularization Investigation (BARI) trial (61). Because BARI patients did not receive the current PCI standard of care, involving the use of drug-eluting stents (DES) and glycoprotein IIa/IIIb antagonists, the results may not be applicable to current practice. Moreover, a subsequent report (25) from the BARI investigators indicated that the survival benefit of CABG was limited to diabetic patients receiving internal mammary artery (IMA) grafts – a finding that has been verified in other trials (54–56). Cardiac mortality after 5.4 years was 2.9% when IMA was used and 18.2% when only saphenous vein graft conduits were used. The latter rate was similar to that in patients undergoing PTCA (20.6%) (57). Currently, there is not enough evidence to suggest whether the advantages of CABG compared with PCI will persist with the use of DES, which markedly reduce the incidence of restenosis and the need for target-vessel revascularization (58).

CABG VERSUS BALLOON-ONLY PCI

Increasing interest in multivessel PCI led to trials of CABG versus angioplasty in the early 1990s (Table 2). These included the Emory Angioplasty versus Surgery Trial (EAST) (59), the Coronary Angioplasty versus Bypass Revascularisation Investigation (CABRI) (60), BARI (61) and the Randomized Intervention Treatment of Angina (RITA)-I trial (62). Too few diabetic patients were enrolled in most of these trials to make a meaningful assessment of its impact on survival (Figure 1).

TABLE 2.

Studies comparing percutaneous coronary intervention (PCI) with percutaneous transluminal coronary angioplasty with or without bare metal stents versus coronary artery bypass grafting (CABG)

Study, year (reference) Patient profile Diabetic population, n
 PCI, % stents CABG, % arterial grafts Mortality, %
PCI CABG PCI CABG
EAST, 1994 (59) Multivessel CAD 29 30 0 86 7 10
CABRI, 1995 (60) Multivessel CAD 62 63 0 81 23 13
BARI, 1996 (61) Multivessel CAD 170 173 0 81 35* 19*
RITA-1, 1993 (62) 1–3 vessel CAD 29 33 98 74 7 10
AWESOME, 2001 (64) Refractory angina 65 79 54 76 19 28
ARTS, 2001 (65) Multivessel CAD 112 96 100 93 6 3
SoS, 2008 (66) Multivessel CAD 68 74 78 81 4 1
ERACI II, 2005 (41,67) Multivessel CAD 39 39 77 89 10 10
MASS II, 2007 (68) Multivessel CAD 56 59 68 92 5 7
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*

P=0.002. ARTS Arterial Revascularization Therapies Study; AWESOME Angina With Extremely Serious Operative Mortality Evaluation; BARI Bypass Angioplasty Revascularization Investigation; CABRI Coronary Angioplasty versus Bypass Revascularization Investigation; CAD Coronary artery disease; EAST Emory Angioplasty versus Surgery Trial; ERACI Argentine Randomized Study: Coronary Angioplasty with Stenting Versus Coronary Bypass Surgery in Multi-Vessel Disease; MASS Medicine, Angioplasty, or Surgery Study; RITA Randomized Intervention Treatment of Angina; SoS Stenting of Saphenous Vein Grafts trial

Figure 1).

Figure 1)

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Mortality outcome in studies comparing percutaneous coronary intervention (PCI) with percutaneous transluminal coronary angioplasty and/or bare metal stents versus coronary artery bypass graft surgery (CABG). ARTS Arterial Revascularization Therapies Study; AWESOME Angina With Extremely Serious Operative Mortality Evaluation; BARI Bypass Angioplasty Revascularization Investigation; CABRI Coronary Angioplasty versus Bypass Revascularization Investigation; EAST Emory Angioplasty versus Surgery Trial; df Degrees of freedom; ERACI Argentine Randomized Study: Coronary Angioplasty with Stenting Versus Coronary Bypass Surgery in Multi-Vessel Disease; MASS Medicine, Angioplasty, or Surgery Study; M-H Mantel-Haenszel method for statistical analysis; RITA Randomized Intervention Treatment of Angina; SoS Stenting of Saphenous Vein Grafts trial

EAST (59) was a single-centre, randomized trial including 392 patients. It compared PTCA (n=198; 49 [24.7%] with diabetes mellitus) with CABG (n=194; 41 [21.2%] with diabetes mellitus) for patients with multivessel CAD (56). Overall, the eight-year survival rate was similar in both groups (79.3% in the PTCA group versus 82.7% in the CABG group; P=0.40). However, survival tended to be greater in diabetic patients who underwent CABG (75.5%) compared with those who underwent PTCA (60.1%; P=0.23). In the angioplasty group, diabetic subjects had a reduced survival rate compared with nondiabetic subjects (60.1% versus 82.6%; P=0.02). By eight years, 26.5% of patients in the CABG group required a repeat revascularization compared with 65.3% of patients in the PTCA group (P<0.001).

CABRI (60) randomly assigned 1054 patients with multivessel disease to PTCA or CABG (left IMA [LIMA] graft: 81%). Diabetic patients had a significantly higher mortality rate than nondiabetic patients, but the difference among diabetic patients treated with PCI (22.6%) or CABG (12.5%; RR: 1.81 [95% CI 0.8 to 4.1]) was nonsignificant.

The BARI trial (61) randomly assigned 1829 patients with multi-vessel disease to CABG (LIMA use: 82%) or PTCA. The study showed similar mortality rates in the overall population (PCI: 13.7% versus CABG: 10.7%; P=0.19), but decreased survival among diabetic patients (n=353) treated with PCI (PCI: 35.5% versus CABG: 19.4%; P=0.003) at five years of follow-up (61).

The RITA-I trial (62) randomly assigned 1011 patients with multi-vessel disease to PTCA or CABG (LIMA graft: 74%), and followed patients for a median of 6.5 years. The study showed no difference in death or MI in the overall population. However, compared with the CABG group, mortality tended to be lower in diabetic patients treated with PCI (24% versus 7%; P=0.09), as did the combined end point of death or MI (36% versus 17%; P=0.06).

A 2003 meta-analysis (63) evaluated 13 randomized trials of nearly 8000 patients who were treated with PTCA or CABG. At long-term follow-up (up to eight years), there was no difference in overall mortality, except for a significantly lower rate with CABG in the subgroup of patients with multivessel disease. PTCA was found to be associated with a marked and significant 24% to 38% increase in revascularization.

CABG versus PCI with bare metal stents

A number of trials have compared CABG versus PCI with bare metal stents (BMS) in diabetic patients (Table 2). Of these, the Stenting of Saphenous Vein Grafts (SoS) trial (66) was the only study that showed significant benefit with CABG in reducing mortality in the diabetic population compared with PCI. Moreover, all of these studies lacked adjunctive pharmacological treatment, including thienopyridine preloading and glycoprotein IIb/IIIa antagonists; therefore, their applicability to current practice is limited.

The Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) trial (64) randomly assigned 454 patients to PCI (stents: 54%) or CABG (LIMA graft: 76%), and 32% (n=144) of these patients had diabetes. At the three-year follow-up, mortality was similar among PCI- and CABG-treated diabetic patients (PCI: 19% versus CABG: 28%; P value nonsignificant). The Arterial Revascularization Therapy Study (ARTS) (65) compared outcomes from bypass surgery versus coronary stenting in patients with multivessel disease. The event-free survival rate at one year was reduced in diabetic patients treated with stenting compared with diabetic patients treated with CABG (63.4% versus 84.4%; P<0.001) and nondiabetic patients treated with stents (76.2%; P<0.04). This difference was largely due to a lower rate of complete revascularization in patients who underwent PCI (70.5%) compared with patients who underwent CABG (84.1%; P<0.001). On the other hand, diabetic and nondiabetic patients experienced similar one-year event-free survival rates when treated with CABG (84.4% and 88.4%, respectively). The five-year mortality rate of diabetic patients in the stent group was 13.4% compared with 8.3% in the surgical group (RR 1.61 [95% CI 0.71 to 3.63]). Within the stent group, the mortality rate of diabetic patients remained higher than that of non-diabetic patients (13.4% versus 6.8%; P<0.03), whereas the cardiac death rates were similar in diabetic (50%) and nondiabetic patients (38%). The mortality rates of diabetic and nondiabetic patients in the surgical group were similar (8.3% versus 7.5%, respectively; P<0.8). In the stent group, repeat revascularizations were performed much more frequently in diabetic (42.9%) than in nondiabetic patients (27.5%; P<0.002), and this difference was reflected by the five-year major adverse cardiac and cerebrovascular event rates of diabetic and nondiabetic patients (54.5% versus 38.7%, respectively; P<0.003) (65).

The SoS trial (66) randomly assigned 988 patients with multivessel disease to treatment with PCI (BMS: 100%) or CABG (LIMA graft: 93%). Among diabetic patients, mortality was 17.6% for PCI-treated and 5.4% for CABG-treated patients, with no evidence that the treatment effect differed among diabetic and nondiabetic patients (interaction test P=0.15).

The Argentine Randomized Study: Coronary Angioplasty with Stenting Versus Coronary Bypass Surgery in Multi-Vessel Disease (ERACI) II (41,67) randomly assigned 450 patients with multivessel disease to undergo PCI (BMS: 100%) or CABG (LIMA graft: 89%). At a five-year follow-up, there were no significant differences in mortality rates among PCI-treated (7.1%) and CABG-treated (11.5%; P=0.18) patients in the overall population, or among diabetic patients (PCI: 10.3% versus CABG: 10.3%).

The Medicine, Angioplasty, or Surgery Study (MASS) II (68) compared PCI (n=205; BMS: 68%) with CABG (n=203; LIMA graft: 92%) and medical treatment (n=203) in patients with multivessel disease. There was no significant difference in mortality between diabetic patients treated with PCI (16.1%) and CABG (15.3%) at five-year follow-up.

SoS (66) was the only trial that showed an increased mortality rate among patients treated with PCI compared with CABG in the overall population (PCI: 10.9% versus CABG: 6.8%; HR 1.66 [95% CI 1.08 to 2.55]; P=0.02) at six years. Comparison of mortality at five years showed similar outcomes among PCI patients enrolled in SoS (8.1%), ARTS (8.0%) and ERACI II (7.1%), whereas the mortality rate among CABG patients was much lower in SoS (4.3%) than in ARTS (7.6%) and ERACI II (11.5%) in the overall population. Of note, mortality in diabetic patients treated with CABG was unexpectedly lower (5.4%) than in nondiabetic patients (7.0%). Fewer repeat revascularizations were required with CABG than with PCI overall at two years, but the diabetic subgroup was not analyzed separately (69). The other trials showed mixed results (64,67,70).

Bravata et al (71) recently reported the largest systematic review comprising 23 randomized controlled trials in which 5019 patients were randomly assigned to PCI (balloon angioplasty or BMS) and 4944 patients were randomly assigned to CABG. Completeness of follow-up was high among all trials, and the follow-up duration extended up to 10 years. Procedural mortality was similarly low for PCI (1.1%) and CABG (1.8%; P value nonsignificant), whereas procedural stroke was more common with CABG (1.2% versus 0.6%; P<0.002). Mortality assessed at one year (PCI: 3.5% versus CABG: 3.6%) and five years (PCI: 10.3% versus CABG: 9.3%) was similar among PCI and CABG in the overall population. However, angina relief was better and repeat revascularization procedures less frequent among CABG- than PCI-treated patients. A subgroup analysis among diabetic patients showed no difference in mortality between PCI (20.8%) and CABG (17.8%, P value nonsignificant) (71).

Another recently published meta-analysis (72), which used pooled patient-level data from 10 long-term randomized trials of 7812 patients with multivessel CAD, evaluated the effect of PTCA or BMS on overall mortality compared with CABG. In the subset of 1233 patients with diabetes, mortality at five years was significantly lower with CABG than with PCI (12.3% versus 20.0%; HR 0.70 [95% CI 0.56 to 0.87]). In comparison, the HR was 0.98 for patients without diabetes. Although DES trials were not included, there appears to be no difference in overall mortality between DES and BMS (73).

CABG versus PCI with DES

DES represent a major advancement for the prevention of restenosis and repeat revascularization after PCI in diabetic patients (74–77). Several registries have compared the clinical outcome of patients with multivessel disease following treatment with DES or CABG (78–86), and these are summarized in Table 3. Three large registries (81,85,86) showed significant benefit with CABG in reducing the incidence of major adverse cardiac events (MACE), while only one (85) showed mortality benefit.

TABLE 3.

Studies comparing percutaneous coronary intervention (PCI) with drug-eluting stents versus coronary artery bypass grafting (CABG)

Study/authors, year (reference) Diabetic population, n
 Mortality, %
 MACE, %
PCI CABG PCI CABG PCI CABG
ARTS II, 2005 (79) 158 96 – – 28 18
ERACI III, 2007 (80) 47 39 – – 36.2 30.8
Ruijin Hospital, 2007 (83) 75 64 – – – –
Lee et al, 2007 (85) 102 103 10 8 27* 12*
Briguori et al, 2007 (84) 69 149 6 5 29 21
Hannan et al, 2008 (86) 344 257 14* 2* 31* 9*
Yang et al, 2008 (81) 163 189 4 4 18* 5*
CARDia, 2008 (87) n=510 3.2 3.3 11.6 10.2
SYNTAX, 2009 (88) 316 314 – – 10.3 10.1
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*

P value for difference between groups was statistically significant. ARTS Arterial Revascularization Therapies Study; CARDia Coronary Artery Revascularization in Diabetes; ERACI Argentine Randomized Study: Coronary Angioplasty with Stenting Versus Coronary Bypass Surgery in Multi-Vessel Disease; MACE Major adverse cardiac event; SYNTAX SYNergy between percutaneous coronary intervention with TAXUS and cardiac surgery trial

ARTS II (79) was a single-arm study of 607 patients (including 159 with diabetes) who were treated with sirolimus-eluting stents; the outcomes were compared with the CABG arm in the ARTS trial (65). To make the results of this registry as comparable as possible with the randomized ARTS trial comparing BMS with CABG, the same inclusion and exclusion criteria, protocol definitions and primary end point were chosen. Nevertheless, compared with ARTS, more patients included in ARTS II had triple-vessel disease, a higher incidence of diabetes, and were treated with more and longer stents. At three years, the incidence of the primary combined end point of death, stroke, MI and repeat revascularization with DES were not significantly different from the CABG arm of ARTS after adjustment for independent predictors (27.7% versus 17.7% for CABG). The composite end point of death, MI or stroke (excluding repeat revascularization) was also similar (9.4% versus 13.5% for CABG).

ERACI III (80) enrolled 225 patients with multivessel disease who were treated with DES, and used the same inclusion and exclusion criteria as the randomized ERACI II trial that compared BMS with CABG. The rate of major adverse cardiac events at three years in ERACI III was significantly higher in diabetic than in nondiabetic patients (36.2% versus 19.1%; RR 0.81 [95% CI 0.66 to 0.99]; P=0.02), with no differences between DES-treated patients in ERACI III (36.2%) and patients undergoing CABG (30.8%) or BMS implantation (43.6%; P=0.49) in ERACI II (67). The need for repeat revascularization was lowest among patients undergoing CABG in ERACI II (15.4%), followed by DES-treated patients in ERACI III (21.3%) and highest among BMS-treated patients in ERACI II (38.5%; P=0.05) (67). Of note, the rate of stent thrombosis in ERACI III amounted to 2.6% after one year, 3.5% after two years and 4.4% by the end of three years.

The Coronary Artery Revascularization in Diabetes (CARDia) trial (87) was a randomized, noninferiority trial that directly compared CABG versus PCI with predominant DES use (71%) in diabetic patients. Due to recruitment difficulties, only 510 of 600 planned patients (85%) were randomly assigned (87). The primary end point, a composite of death, nonfatal MI and stroke assessed at one year, showed similar outcomes for PCI (11.6%) and CABG (10.2%; P=0.63), with no significant differences in rates of death (PCI: 3.2% versus CABG: 3.3%; P=0.83) or MI (PCI: 8.4% versus CABG: 5.7%; P=0.25), although nonfatal strokes tended to be less common with PCI (0.4%) than with CABG (2.5%; P=0.09). Repeat revascularization procedures were more frequent with PCI (9.9%) than with CABG (2.0%; P<0.001) at one-year follow-up. These findings were similar to the subgroup of diabetic patients with multivessel disease included in the SYNergy between PCI with TAXUS and cardiac surgery (SYNTAX) trial (88), a large-scale randomized study (n=1800 patients) comparing CABG versus PCI with DES. The composite end point of death, MI or stroke at one year was similar for CABG (10.3%) and PCI (10.1%; P=0.96), whereas repeat revascularization was more common after PCI (PCI MACE: 26.0% and CABG MACE: 14.2%; P=0.03) (88).

The recently published BARI 2 Diabetes (BARI 2D) trial (89) included 2368 patients with stable ischemic heart disease assigned before randomization to PCI or CABG. No significant differences were found in the primary end point of all-cause mortality or the principal secondary end point of all-cause death, MI or stroke between patients with type 2 diabetes mellitus undergoing revascularization and those undergoing intensive medical therapy, or between strategies of insulin sensitization and insulin provision therapy. A subanalysis showed that in the CABG stratum, a significant reduction in major cardiovascular events (all-cause mortality, MI or stroke) was seen with CABG compared with intensive medical therapy, largely because of a reduction of MI in patients within the insulin sensitization strategy (90). However, compared with patients selected for PCI, CABG patients had, on average, more three-vessel disease (52% versus 20%; P<0.001), more total occlusions (61% versus 32%; P<0.001), more proximal left anterior descending artery stenosis of 50% or greater (19% versus 10%; P<0.001), a greater number of nonobstructive and obstructive atherosclerotic and class C lesions (P<0.001), and an increased cardiac death rate.

Possible mechanism of benefit with CABG

The only difference between the diabetic groups in the BARI study (61) was the revascularization procedure chosen. Hence, the prognostic difference is likely to be related to the relative efficacy of these revascularization procedures. The major advantage of CABG over PTCA is the ability to achieve complete revascularization (91,92). The superiority of CABG over angioplasty in providing complete revascularization is exemplified in the BARI study itself. In the BARI population, 3.1 grafts were placed per patient undergoing CABG (93), whereas the mean number of successfully treated lesions in the PTCA group was two (29). Similar numbers were reported by other studies (94–96) comparing multivessel angioplasty and CABG. When multivessel angioplasty is performed, multiple treatment sites can independently result in restenosis (97); therefore, it is likely that this goal is frequently not achieved in diabetic patients given their high restenosis rates. Thus, the poorer outcome of diabetic patients undergoing PCI may be mediated, in part, by the frequent occurrence of incomplete revascularization (94). Van Belle et al (24) suggested that restenosis, especially in its occlusive form, is a major determinant of long-term mortality in diabetic patients after coronary angioplasty. These investigators studied 604 diabetic patients who underwent angioplasty, followed by a six-month follow-up angiogram and long-term follow-up. They found that the group, which had no restenosis, had a 10-year mortality rate of 24% compared with a 35% mortality rate in the group with nonocclusive restenosis and a 59% mortality rate in the group with occlusive restenosis (P<0.0001) (26,98). The impact of incomplete revascularization may be more pronounced in view of the more diffuse and distal CAD (26,98) and worse coronary vasodilator reserve in diabetic patients (99). Thus, PTCA, rather than leading to increased mortality, may fail to alter the aggressive natural course of CAD in diabetic patients (29).

CONCLUSION

Diabetic patients experience more extensive atherosclerosis and a worse clinical outcome following revascularization procedures. In recent years, technical advances have resulted in improved outcomes after coronary revascularization with PCI or CABG. Much of the evidence comparing PCI with CABG comes from older studies of PTCA, which did not use current recommended antiplatelet therapies and aggressive secondary preventive strategies postrevascularization. Data to guide decision making are limited regarding the current choice between CABG and PCI using DES and newer antiplatelet agents in diabetic patients with multivessel CAD. Although CABG remains the standard of care for most diabetic patients with multivessel CAD, the paradigm may begin to shift. Further follow-up from the initial stent versus CABG studies will offer insight; however, the field has already begun to move beyond these trials. Data from randomized controlled trials comparing DES with CABG in patients with diabetes, such as Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease (FREEDOM) (100), CARDia (87) and ARTS II (79) – may help clarify this issue. Additionally, greater and more sustained use of both intravenous and oral antiplatelet agents, and the use of hybrid operative and PCI procedures will also change practice patterns in the coming years.

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