Chapter 19. Indications for Revascularization

Coronary artery disease remains the most common pathology with which cardiologists and cardiac surgeons are faced. Accordingly, the practicing cardiac surgeon is confronted with no clinical question more often than, “Is coronary bypass indicated in this patient?” It is the aim of this chapter to provide a practical overview of the current indications for myocardial revascularization with sufficient reference to the relevant studies on which they are based to afford the reader an appreciation for the strengths and limitations of their conclusions.

A surgeon's first introduction to a patient with coronary artery disease is frequently an angiogram. In addition to the coronary anatomy, however, the clinical presentation and results of noninvasive studies of myocardial perfusion and function are necessary to characterize the pathophysiologic implications of the angiographic disease and its impact on prognosis and, therefore, to make a clinically appropriate recommendation. In the technological era in which we practice, the importance of the clinical history bears emphasis—particularly in an aging population. Because one of the objectives of surgery is to improve symptoms and quality of life, a thorough appreciation of the patient's functional status is a prerequisite in selecting the optimal therapeutic strategy.

The system proposed by the Canadian Cardiovascular Society for grading the clinical severity of angina pectoris is widely accepted (Table 19-1). Unfortunately, angina is a highly subjective phenomenon for both patient and physician, and prospective evaluation of the assessment of functional classification by the CCS criteria has demonstrated a reproducibility of only 73%.1 Furthermore, there may be a strikingly poor correlation between the severity of symptoms and the magnitude of ischemia, as is notoriously the case among diabetic patients with asymptomatic “silent ischemia.”

Electrocardiography (ECG), if abnormal, is helpful in assessing ischemic burden. Unfortunately, it demonstrates no pathognomonic signs in half of patients with chronic stable angina. Still the monitoring of an ECG under stress conditions is simple and inexpensive, and is therefore useful as a screening examination. Among patients with anatomically defined disease, stress ECG provides additional information about the severity of ischemia and the prognosis of the disease. The sensitivity of the test increases with age, with the severity of the patient's disease, and with the magnitude of observed ST-segment shift.2 If ST- segment depression is greater than 1 mm, stress ECG has a predictive value of 90%, whereas a 2-mm shift with accompanying angina is virtually diagnostic.3 Early onset of ST-segment depression and prolonged depression after the discontinuation of exercise are strongly associated with significant multivessel disease. Unfortunately, many patients cannot achieve their target heart rates owing to beta blockade or a limitation to their exercise tolerance caused by coexisting disease, decreasing the usefulness of this test in these often high-risk patients. Resting abnormalities in the ECG may also limit the predictive accuracy of the test.

Perfusion imaging with thallium-201 or a technetium-99m–based tracer may be particularly useful in patients with abnormalities on their baseline ECG. Reversible defects demonstrated by comparison of images obtained after injection of the tracer at peak stress with rest images is indicative of ischemia, and hence viability. An irreversible defect indicates a nonviable scar. The results obtained with both tracers are similar, with the average sensitivity around 90% and specificity of approximately 75%.4 For patients unable to exercise, pharmacologic vasodilators such as adenosine or dipyridamole may be used with similar sensitivity.5

Echocardiographic imaging during exercise or pharmacologic stress has gained increasing popularity among cardiologists. Comparative studies have demonstrated accuracy similar to that of nuclear studies with sensitivity and specificity both around 85%.4 Patients unable to exercise may be stressed with high-dose dipyridamole, or more commonly dobutamine at doses from 5 to 40 μg/kg/min. An initial augmentation of contractility followed by loss or “drop out” is diagnostic of ischemia (and accordingly viability), whereas failure to augment contractility at low dose suggest scar. Additionally, information regarding concomitant valvular disease may be obtained during the examination.6

The guidelines for surgical revascularization established by the American College of Cardiology and American Heart Association are shown in Table 19-2.7 The basis for these guidelines resides in the large body of literature comparing medical therapy with surgical revascularization and, more recently, percutaneous coronary interventions (PCI).

Before reviewing the results of the seminal trials of CABG versus medical therapy performed in the 1970s and those of newer prospectively randomized trials comparing the results of surgery with PCI and medical therapy, some limitations of these trials must be recognized. First, in retrospective or registry studies, it is difficult to ensure comparable patient populations by virtue of the extraordinary anatomical and physiologic complexity of coronary artery disease as well as the heterogeneity of the patient substrate. Differences in ventricular function and comorbidities such as age, diabetes, peripheral vascular disease, and pulmonary disease may have a profound impact on outcomes such as survival or quality of life. For example, caution must be exercised in interpreting the results of nonrandomized and registry reports of PCI versus surgery, because the patients subjected to the former more often have single- or double-vessel disease,8,9 whereas the latter commonly have triple-vessel or left main disease.8,9 Attempts to correct for selection bias with statistical techniques such as propensity matching are only as valid as the parameters entered into the model. Data less tangible than gender or chronologic age, such as socioeconomic status or “physiologic age,” are not easily accounted for in such analyses and yet may be a critical determinant of outcomes. Despite this limitation, retrospective and registry data provide a better glimpse of the real world of coronary artery disease. Most prospective randomized trials include only a fraction of the total population undergoing revascularization by virtue of strict entry criteria. For example, the Bypass Angioplasty Revascularization Investigators (BARI) trial entered only 5% of total patients screened.10 Therefore, although the prospectively randomized studies do provide objective data directly applicable to the specific patient subset represented in the study, extrapolation of the results to the more heterogeneous populations seen clinically can only be made if the implicit caveats are clearly understood. We must be mindful of the inescapable tradeoff between selection bias in registry studies and entry bias in randomized studies.

Second, as a consequence of the overrepresentation of patients at lowest risk of death in randomized trials, most are statistically underpowered with respect to survival analysis. For example, given current survival statistics, we would need approximately 2000 patients in each arm of a study to detect a 30% difference in mortality. The problem is compounded by the exclusion of the very patients for whom one would anticipate a survival advantage with adequate revascularization, such as those with depressed ventricular function. Randomized studies frequently employ softer end points such as angina or quality of life, or create composites of qualitatively different end points, such as death, stroke, and myocardial infarction (MI). Meaningful analysis is further complicated by relatively short-term follow-up in most studies. Events such as the need for subsequent revascularization and recurrence of angina characteristically occur at different time intervals after these therapies (restenosis after PCI versus graft occlusion after CABG), and an 8- to 10-year follow-up period is needed to adequately compare long-term results. Patients themselves are also generally interested in outcomes measured in years, not months.

Significant improvements in each of the treatment strategies for coronary artery disease are occurring constantly. Examples include the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, lipid-lowering therapy, internal thoracic aortic (ITA) grafts, intravascular stents, and the development of drug eluting stents. These advances, along with aggressive secondary prevention after revascularization, have steadily reduced the morbidity and mortality of coronary artery disease in all patients, making differences in the hard end point of survival difficult to demonstrate for any therapy.11 This trend will likely increase as the beneficial effect of secondary prevention becomes more widely appreciated.

Medical Therapy

In the decades since coronary artery bypass (CABG) surgery was popularized and coronary angioplasty introduced, an enormous volume of data on the results of invasive revascularization has been collected. Remarkably, almost from the outset many of these studies have been prospectively randomized. Yet in the current era there is a dearth of data concerning pharmacologic therapies for chronic coronary artery disease despite remarkable recent drug development. For example, although nitrates are unquestionably effective in relieving symptoms, the impact of long-acting nitrates on clinical outcomes has never been rigorously tested. Furthermore, there has been only one trial of beta-blocker therapy in the treatment of angina, the Atenolol Silent Ischemia Study (ASIST), which demonstrated benefit for patients with mild effort induced angina or silent ischemia.12 A handful of studies of combination therapy with beta blockers and calcium channel blockers have also demonstrated antianginal benefit.13–15

Surgical versus Medical Therapy

Three major randomized studies, the Coronary Artery Surgery Study (CASS),16 the Veterans Administration Cooperative Study Group (VA),17,18 and the European Coronary Surgery Study (ECSS),19,20 as well as several other smaller randomized trials,21–23 conducted between 1972 and 1984, provide the foundation for comparing the outcomes of medical and surgical therapy. Despite the limitations noted in the preceding, these studies are remarkably consistent in their major findings, and the qualitative conclusions drawn from them continue to be generalizable to current practice.

The central message from all of these studies is that the relative benefits of bypass surgery over medical therapy on survival are greatest in those patients at highest risk as defined by the severity of angina and/or ischemia, the number of diseased vessels, and the presence of left ventricular dysfunction.24 For example, thus far, no study has shown survival benefit for CABG over medical therapy for patients with single-vessel disease. It should be emphasized, however, that these trials involved primarily patients with moderate chronic stable angina. These conclusions may, therefore, not necessarily apply to patients with unstable angina or to those with more severe degrees of chronic stable angina.

A meta-analysis of the seven randomized trials cited in the preceding demonstrated a statistically enhanced survival at 5, 7, and 10 years, for surgically treated patients at highest risk (4.8% annual mortality) and moderate risk (2.5% annual mortality), but no evidence of a survival benefit for those patients at lowest risk.24 The overall survival benefit at 12 years for the three large and four smaller randomized studies is shown in Fig. 19-1. Nonrandomized studies have also demonstrated a beneficial effect of surgery on survival of patients with multivessel disease and severe ischemia regardless of left ventricular function.25–28

There have been three recent randomized controlled trials of invasive revascularization by PCI or CABG versus medical therapy. Their results make an even stronger case for revascularization. In the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial, patients with anatomy amenable to CABG were randomized to angina-directed anti-ischemic therapy, drug therapy guided by noninvasive measures of ischemia, or revascularization by CABG or PCI.29 At 2 years, there was a statistically significant difference in mortality of 6.6% in the angina-guided group, 4.4% in the ischemia-guided group, and 1.1% in the revascularization group. The rates of death or MI were also statistically different at 12.1%, 8.8%, and 4.7%, respectively. The Medicine, Angioplasty, or Surgery Study (MASS-II) trial randomized patients with multivessel disease among medical therapy, PCI, and CABG. Although survival at 1 year was equivalent, freedom from additional intervention was 99.5% for surgical patients and 93.7% for medically treated patients. Reintervention was, incidentally, even higher in the PCI group than the medical group, with 86.7% free of additional intervention. Angina was superior in the CABG group (88%) than in the PCI group (79%) or medical therapy group (46%).30

In the Trial of Invasive versus Medical Therapy in Elderly Patients with Chronic Symptomatic Coronary-Artery Disease (TIME) study, elderly patients were studied with chronic angina. This failed to demonstrate a difference between optimized medical therapy and an invasive revascularization strategy (PCI or CABG) in terms of symptoms, quality of life, and death or nonfatal myocardial infarction (20% versus 17%, p = .71). However, medically treated patients were at higher risk because of major clinical events (64% versus 26% for invasive, p < .001), which were mainly attributable to rehospitalization and revascularization.31 In this trial of severely symptomatic elderly patients, it was encouraging that the price of an initially conservative strategy, followed by crossover to revascularization in approximately 50% of patients, was not paid for in terms of death or myocardial infarction.31

Early concern over a prohibitive operative mortality among patients with impaired ventricular function has been superseded by the recognition that the survival of these patients on medical therapy was much worse than their survival with revascularization. This, coupled with ever-improving surgical techniques, such as advances in myocardial preservation and perioperative support, has made this specific subgroup the one in which the relative survival benefit of surgical therapy is the greatest. Accordingly, left ventricular dysfunction in patients with documented ischemia is now considered an important indication—rather than contraindication—for surgical revascularization.16,24,25,32 Recent evidence that ischemic, viable, hypokinetic myocardium (hibernating or stunned) regains stronger contractile function after effective revascularization, has prompted expansion of the indications for surgical revascularization among patients with severe left ventricular dysfunction to include patients who would otherwise be considered candidates for cardiac transplantation. This subject is discussed in more detail in the following.

In summary, in regard to chronic stable angina, a survival advantage is demonstrable for surgical revascularization over medical therapy in patients with: left main disease;33 triple-vessel disease and left ventricular dysfunction;34,35 two-vessel disease and proximal LAD disease;36 and severe ischemia and multivessel disease (Fig. 19-2).37,38 Those survival advantages have not been demonstrable among patients with single-vessel disease.39–41

Apart from affording a survival benefit, CABG is indicated for the relief of angina pectoris and improvement in the quality of life. Between 80 and 90% of patients who are symptomatic on medical therapy become symptom-free after CABG. This benefit extends to low-risk patients for whom survival benefit from surgery is not likely.24 Relief of symptoms appears to relate to both the completeness of revascularization and maintenance of graft patency, with the benefit of CABG diminishing with time. Recurrence of angina following CABG surgery occurs at rates of 3 to 20% per year. Although enhanced survival is reported when an ITA graft is used to the LAD, there is no significant difference in postoperative freedom from angina.41 This may be because of vein graft occlusion or progression of native disease in grafted or ungrafted vessels.17

Unfortunately, few patients experience an advantage in work rehabilitation with surgery as compared with medical management. Generally, employment declines in both groups and is determined nearly as much by socioeconomic factors as age, preoperative unemployment, and type of job as by type of therapy or clinical factors such as postoperative angina. Notably, surgical revascularization has not been shown to reduce the incidence of nonfatal events such as myocardial infarction (MI), although this may be because of perioperative infarctions that offset the lower incidence of infarction in each study follow-up.26,42

PCI versus Medical Therapy

Despite the increasing application of catheter-based technology to multivessel disease, the majority of interventions have historically been in single-vessel disease. Accordingly, most of the data comparing angioplasty with medical therapy are derived from studies comprised principally or exclusively of patients with a limited extent of obstructive disease, although most people with angiographically detectable stenosis in one vessel have more extensive atherosclerotic changes throughout most of their coronary vessels. Many of these trials also antedate the use of IIb/IIIa inhibitors, clopidogrel, and stents. Although angiographic success rates of 85 to 90% are commonplace, no study to date has ever shown a benefit in survival or subsequent MI for PCI over medical therapy in patients with stable angina pectoris. However, the results of several recent studies have demonstrated improvement in symptoms and exercise tolerance.

In the ACME (A Comparison of angioplasty with MEdical therapy)–I study, 212 patients with documented ischemia and a single coronary artery stenosis greater than 70% were randomly assigned to medical therapy or angioplasty.43 After 6 months, there was no mortality difference in either treatment group; however, PCI provided more complete angina relief with fewer medications and better quality of life scores, as well as longer exercise duration on stress testing than medical therapy.43 This benefit came at some cost, however; among the 100 angioplasty patients, 19 underwent repeat PCI and seven underwent CABG during the first 6 months, compared with 11 angioplasty procedures and no CABG surgery in the patients randomized to medical therapy.43 Moreover, nearly half of all patients assigned to initial medical therapy were asymptomatic at 6 months. Because this modest symptomatic benefit was achieved at such a large procedural and financial cost, patients who are either asymptomatic or have mild symptoms should have objective evidence of ischemia before PCI.44 In a follow-up study by the same investigators, 101 patients with stable angina and two-vessel disease were randomized to PCI or medical therapy.45 At 6 months, both groups had similar improvement in exercise duration, freedom from angina, and overall quality of life. These studies together suggest that, in many patients, an initial trial of medical therapy is appropriate.

Several other studies have included patients with multivessel disease. In the Randomized Intervention Treatment of Angina (RITA)–2, of 1018 patients with stable angina randomized to medicine or PCI, one-third had two-vessel disease and 7% had three-vessel disease.46 Perhaps surprisingly, at a median follow-up of 2.7 years, the primary end points of death or MI had occurred twice as often in the PCI group (6.3 versus 3.3%, p < .02). Surgical revascularization was required during the follow-up interval in 7.9% of the PCI group and repeat angioplasty was required in 11%. In the medical group, 23% of patients required revascularization. Angina relief and exercise tolerance were improved to a greater degree in the angioplasty group early, but this difference disappeared by 3 years. These results are echoed in the MASS-II trial, in which angina relief was superior with PCI, but rates of intervention/reintervention were actually higher in the PCI group.30 Again, this supports an initial strategy of medical therapy.

A comparison of PCI versus medicine as initial strategy among patients with hyperlipidemia was examined in the Atorvastatin versus REvascularization Trial (AVERT).47 Among 341 patients with one- or two-vessel disease, ischemic events were actually less common in the medical than PCI groups (13% versus 21%, p < .05). Although criticized for employing outdated angioplasty technology and other issues, the results of this study are consonant with the demonstration that lipid-lowering agents may have a powerful impact on ischemic events.48 In some respects, the lower use of aggressive lipid-lowering agents in the PCI arm biased the results in favor of medical therapy.

The most recently published trial, COURAGE, randomized 2287 patients with stable angina and objective evidence of ischemia to best medical therapy or PCI and medical management. All patients received long-acting metoprolol, amlodipine, and/or isosorbide mononitrate, as well as lisinopril or losartan. Patients had aggressive antilipid therapy and appropriate antiplatelet therapy. The primary finding of this trial was a lack of benefit of PCI over best medical therapy for death, myocardial infarction, or other major cardiovascular events.49 Although this result has caused much controversy in the cardiology community, it is consistent with older studies.

A meta-analysis of percutaneous interventions versus medical management was published in 2005.50 In patients with stable coronary artery disease, no benefit was found for invasive therapy in terms of death, MI, or need for subsequent revascularization. These studies provide compelling evidence that, thanks to substantial improvements in medical management, all patients should have a trial of optimized medical therapy before invasive intervention.

PCI versus CABG

Randomized Studies

A number of studies comparing an initial strategy of angioplasty versus early surgery have been carried out, all with similar results. It is important to recognize that these studies are comparisons of treatment strategies and not head-to-head comparisons of revascularization techniques. Accordingly, crossover is permitted and end points are selected to determine adverse consequences of the algorithm on an “intention to treat” basis.

A single-center Swiss study of 134 patients with isolated LAD disease was reported in 1994.51 At 2.5 years of follow-up there was no significant difference in combined outcomes of MI and cardiac death between treatment groups. There was, however, a greater need for surgical revascularization in the initial PCI treatment group, with 25% requiring a second revascularization procedure compared with only 4.4% in the initial CABG group. Although the PCI patients were taking significantly more antianginal medication, clinical impairment level, stress test performance, and quality-of-life indices did not differ at 2 years. These findings held up at 5 years52 with no difference between groups with respect to mortality or functional outcome despite repeat procedures in the PCI group.

The Medicine, Angioplasty or Surgery Study (MASS) from Brazil compared medical therapy, PCI, and CABG using an ITA bypass at a single center in 214 patients with stable angina, normal left ventricular function, and proximal stenosis of the left anterior descending coronary artery.53 In this relatively small but nonetheless important randomized trial, the combined end point of cardiac death, MI, or refractory angina requiring revascularization was statistically significantly less in surgically treated patients. Moreover, there was no significant difference between patients treated medically or with PCI. In comparison with medical therapy, however, both PCI and CABG surgery were shown to provide improved relief of severe symptoms of angina pectoris and a lower frequency of inducible ischemia on treadmill exercise testing. There was no difference among the three strategies with respect to mortality or late MI at 1 year. Similar findings were obtained at 5-year follow-up.54

The results of the second MASS trial, which enrolled 611 patients with multivessel disease, reported 1-year outcomes as noted in the preceding.39 Although technology is a moving target, this trial has the advantage that approximately 70% of PCI patients had stents placed. Despite this, the results were remarkably similar to MASS, with a lower incidence of adverse events in the medical group than PCI group. Surgical therapy provided the best angina relief and lowest incidence of adverse events. All therapies had similar survival rates.

A number of larger prospectively randomized studies comparing PCI with CABG have been reported in recent years. All share the limitation that, in general, only a very small minority of patients undergoing revascularization at any center were entered into these trials.55,56 Accordingly, the populations included in the trials may not be generally reflective of clinical practice. For instance, few patients in these studies had significant LV dysfunction and most randomized patients had only one- or two-vessel disease. In the RITA trial, approximately one-third of patients had single-vessel disease.57 Among clinically eligible patients in the Bypass Angioplasty Reperfusion Investigation (BARI)39 and Emory Angioplasty versus Surgery Trial (EAST)40 trials, approximately two-thirds of patients were excluded on angiographic grounds that included chronic total occlusion, left main coronary artery stenosis, diffuse disease, or other anatomical factors making PCI potentially dangerous. Consequently these randomized trials contain only a portion of the spectrum of patients with coronary artery disease encountered clinically. Entry bias has a significant impact on the likelihood of observing an outcome difference among therapies. Because a high proportion of the randomized patients are in the low-risk group, it is possible that any potential survival benefit of CABG surgery over PCI in high- and moderate-risk groups may be masked.56

A second consideration in evaluating these studies is that the success of revascularization procedures depends not only on the criteria employed to define success, but also on the interpretation of those criteria by both patient and physician. In the 1985 to 1986 National Heart, Lung, and Blood Institute PCI Registry, 99% of patients were discharged alive from hospital, and 92% did not sustain a MI or require CABG surgery.58 In the BARI trial, 99% of patients survived hospitalization and 88.6% of PCI-treated patients did not have MI or require repeat revascularization by angioplasty or surgery during the initial hospitalization.39 Employing event-free criteria (death, MI, CABG) for the initial hospitalization, PCI can be judged successful. However, if a repeat revascularization procedure within 5 years is regarded as a negative outcome, then far fewer patients are treated successfully. Regardless, the lack of differences in mortality or MI rates permits individuals to select one or the other procedure as initial therapy without the likelihood that they will pay a price with their health.

In the BARI, EAST, RITA, CABRI, and GABI multivessel PCI versus CABG surgery trials,39,40,57,59,60 mortality was similar between 1 and 5 years of follow-up in both the PCI and CABG treatment groups. Mortality ranged from 3% in the CABRI trial at 1 year follow-up59 and 3.4% in the RITA trial at 2.5 years57 to 13% in the BARI trial at 5 years.61 A slightly higher incidence of MI was noted in some of these trials.

The incidence of repeat revascularization is higher among patients treated with angioplasty than surgery in all trials carried out to date, ranging from 36.5% in the CABRI trial at 1 year follow-up to 62% in the EAST trial at 3 years. Repeat revascularization in the EAST trial for angioplasty-treated patients was much higher than that in the BARI, CABRI, and RITA trials. In contrast with PCI, repeat revascularization is less common after CABG in these same studies. The incidence of repeat revascularization procedures in multivessel patients randomized to CABG surgery ranged from 3.5% in the CABRI trial to 13.5% in the EAST trial.40,59 Generally, repeat revascularization procedures were required five to eight times more often in patients with multivessel disease initially treated with angioplasty as compared with those randomized to initial CABG surgery. The incidence of angina at follow-up also was generally greater in the PCI-treated patients.

In the BARI trial at 5 years, 54.5% of patients initially assigned to PCI had undergone a repeat revascularization procedure, including repeat PCI in 23.2%, CABG in 20.5%, and both in 10.8%.61 Among angina-free patients at 5 years, only 48% of the angioplasty-treated patients compared with 94% of the CABG surgery patients had not had an additional revascularization procedure after their initial procedure. An important subgroup analysis of the BARI trial demonstrated a marked survival benefit with surgery for patients with insulin-dependent diabetes receiving an ITA.

Several more recent studies of PCI versus surgery have confirmed these findings. The Argentine Randomized Trial of Coronary Angioplasty versus Bypass Surgery in Multi-vessel Disease (ERACI) trial conducted between 1998 and 1990 demonstrated no difference in death or MI, but superior event-free survival in the CABG group at 1 and 3 years.62,63 In the French Monocentric Study, 152 patients with multivessel disease underwent PCI or CABG.64 Again, superior event-free survival was seen in the surgical group, driven predominantly by a lesser need for subsequent revascularization.

The impact of advanced stent technology on the comparative results of PCI and CABG has been recently investigated as well. In the Arterial Revascularization Therapy Study (ARTS), 1205 patients with multivessel disease underwent CABG or PCI with bare-metal stents.65 No significant differences in the primary end point of freedom from death, stroke, or MI at 1 year were observed, although the need for revascularization remained higher in the angioplasty than surgery groups. Similarly the second Argentine Randomized Trial of Coronary Angioplasty versus Bypass Surgery in multivessel disease (ERACI II) study group66 demonstrated that, even with the use of stents, repeat revascularization was more common in the PCI group, particularly among diabetics in whom repeat revascularization was required in 22.3% versus 3.1% in the CABG group. Of note, in this study, the 30-day mortality was higher in the CABG than PCI group, as was the incidence of Q wave MI. Despite a high operative mortality rate (5.7%) in the surgery group that raised many questions, at 5 years, there was no difference in survival and again, CABG patients had a lower incidence of revascularization. The Surgery Or Stent (SOS study), which compared outcomes in almost 1000 patients with multivessel disease, demonstrated similar all-cause mortality among surgical compared to angioplasty patients and confirmed higher rates of repeat revascularization after angioplasty and lower freedom from angina pectoris in both patients with and without a recent acute coronary syndrome.67 Of interest in this study, the reintervention rate, while still higher than after surgery, was far below that previously reported for angioplasty at only 17%. Mercado et al. performed a meta-analysis of the ARTS, ERATSII, MASSII, and SOS trials that demonstrated similar rates of death, MI, or stroke at 1 year and higher repeat revascularization rates with PCI.68 A meta-analysis of 5-year data was also recently published, confirming the 1-year results with repeat revascularization more frequent after PCI than CABG (29% versus 7.9%, p < .001) (Fig. 19-3).69

The most recent trial, the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial, assessed the optimal revascularization strategy for patients with three-vessel or left main coronary artery disease by randomizing 1800 patients to either CABG or drug-eluting stents.70 At 12 months, the rates of myocardial infarction and death were similar between groups, but stroke was significantly more common in the CABG patients (2.2% versus 0.6% at 1 year). It should be noted that the CABG group had much less aggressive medical management postoperatively, including fewer patients on antiplatelet medications, which may account for some of the increase in stroke risk. Despite the use of DES, the rates of reintervention were still significantly higher (13.5% versus 5.9%) in the PCI group than the CABG group. Because of the lack of difference in early mortality and myocardial infarction, some cardiologists have begun to suggest that left main should no longer be an indication for CABG.71 However, others maintain that the evidence for PCI is still inadequate and that the greater freedom from reintervention with CABG suggests that CABG remains the treatment of choice for patients with left main disease.72

In conclusion, the randomized trials of PCI versus CABG are useful, but only if results are interpreted in a context of patients entering or eligible to enter these trials.55,56 PCI is a reasonable alternative to CABG surgery, and for many patients it is the preferred initial approach, provided the patient understands that there may be a higher incidence of recurrent angina and need for repeat revascularization procedures, as well as a year-long commitment to use of clopidogrel because of concern regarding catastrophic late stent thrombosis. For most patients similar to those included in these published trials, it is reassuring that a nonsurgical revascularization procedure does not place them at increased risk of MI or death in comparison with the outcomes of surgical therapy. To extrapolate these results to patients who would not have met entry criteria, however, it is intellectually flawed and potentially misleading.

Nonrandomized Database Comparisons

The information provided by randomized studies is complemented by information gleaned from large, prospectively managed, nonrandomized database studies. Such registries provide insight into the management of the sizeable population of patients who would not have been eligible for randomization. The Duke Cardiovascular Disease Databank followed 9263 patients undergoing clinically indicated coronary angiography between 1984 and 1990 for a mean of 5 years after nonrandomized treatment by CABG, PCI, or medical therapy.9 Patients with valvular disease, prior revascularization, significant (>75%) left main disease, and congenital and nonischemic cardiomyopathy were excluded. Overall, 39% of the patients had one-vessel disease, 31% two-vessel disease, and 30% three-vessel disease. Initial therapy was medical in 3053 patients, PCI in 2788 patients, and CABG in 3422 patients. To correct for baseline differences among treatment groups, a standard covariate adjustment was performed that included all identified prognostic factors in a multivariate survival model. Complete follow-up was obtained in 97% of patients. The 5-year survival was 91%, remarkably similar to that reported from Emory, which showed an overall adjusted 5-year survival rate of 93% in both groups.32 The mortality hazard ratios derived from the Cox regression model to evaluate relative survival differences in this database study are shown for medicine versus CABG surgery in Fig. 19-4, PCI versus medicine in Fig. 19-5, and PCI versus CABG in Fig. 19-6.9

From a practical standpoint, in this database study and in the randomized trials, the effect of revascularization on survival depended largely on the extent of the coronary artery disease and is an example of the concept of benefit in relationship to a “gradient of risk.” For the least severe (one-vessel) disease, there were no survival advantages of revascularization over medical therapy in up to 5 years of follow-up.9 For intermediate levels of coronary artery disease severity (ie, two-vessel disease), there was a higher 5-year survival rate for patients undergoing revascularization than for those treated medically. For patients with the most-severe coronary artery disease (ie, three-vessel disease), CABG surgery provided a significant and consistent survival advantage over medical therapy. PCI appeared prognostically equivalent to medical therapy in these patients, but only a small number of patients in this subgroup underwent angioplasty. In comparing PCI with CABG surgery, PCI demonstrated a small survival advantage over CABG surgery for patients with less-severe two-vessel disease, whereas CABG surgery was superior for more severe two-vessel disease (ie, proximal left anterior descending artery involvement).9

These important findings have been confirmed in the current era of PCI with stent implantation using the New York State Database published in 1999 using cases from 1993 to 1995.73 In this study, a survival benefit was observed with angioplasty at 3 years for those patients with single-vessel disease not involving the LAD, whereas those with LAD or three-vessel disease had superior outcomes with surgery. In the more recent study of patients with multivessel disease who received PCI, survival was higher among the 37,212 patients who underwent CABG than among the 22,102 patients who underwent stent placement after adjustment for known risk factors. The adjusted hazard ratio for the long-term risk of death after CABG relative to stents was 0.64 (0.56 to 0.74) for three-vessel disease and proximal LAD disease. This hazard ratio increased to 0.76 (0.60 to 0.96) for patients with two-vessel disease and LAD involvement74 (Fig. 19-7). This study has limitations of being a nonrandomized study and subject to bias; however, the surprising finding of a survival advantage apparent as early as 3 years postprocedure suggests that improvements in cardiac surgical anesthetic care, myocardial protection, and intensive care management have at least matched if not surpassed advances in percutaneous technology. It is important to note that PCI targets the culprit lesion. In contrast, CABG surgery targets both the culprit lesion and potential future culprit lesions by bypassing the diseased vessel. This in part may explain the apparent mortality benefit derived with CABG (Fig. 19-8).75

Acute Coronary Syndromes

The acute coronary syndromes (ACS) cover a wide spectrum from ST-segment elevation MI with underlying coronary obstruction to Prinzmetal's or variant angina in patients with coronary vasospasm in the absence of significant underlying obstruction. The term non–ST-segment elevation ACS encompasses the entities of unstable angina, non–Q wave MI, and postinfarction angina. They denote acute, symptomatic imbalances of the myocardial oxygen supply-demand ratio over a short time span. Prinzmetal angina, or coronary vasospasm, is diagnosed definitively by electrocardiograms obtained during the episode of pain and is treated medically. Unstable angina is not a uniform clinical entity, but comprises the spectrum of myocardial ischemia between chronic stable angina and MI, and is defined as a recent change in the severity, character, or trigger threshold of chronic stable angina or new-onset angina. Approximately 5.6 million Americans have chronic angina, and about 350,000 develop new-onset angina each year. Unstable angina develops in approximately 750,000 Americans each year and is associated with subsequent MI in approximately 10%. Postinfarction angina is defined as the presence of angina or other evidence of myocardial ischemia in a patient with a recent (1- to 2-week) Q wave or non–Q wave MI.

The initial approach to the patient with non–ST-segment elevation ACS (NSTEMI) is pharmacologic stabilization followed by risk stratification. The latter is based on multiple clinical, demographic, and ECG variables in addition to the use of serum biomarkers. In institutions with facilities for early angiography, patients at intermediate or high risk (the majority) undergo early angiography with a view to revascularization. In many parts of the world, however, angiographic facilities are limited and an alternative approach based upon pharmacologic stabilization followed by mobilization and risk stratification using stress testing is employed.

The most recent randomized controlled trials of aggressive versus conservative approaches to non–ST-segment elevation ACS are the FRISC II, TACTICS, and VINO trials.76–78 Despite differences between these trials, the results favor an aggressive strategy with a view toward revascularization in the majority of the patients shown to be at high risk (eg, older patients, diabetics, those with ST-segment depression on ECG, and those with elevated CPK-MB or serum troponins).

CABG versus Medical Therapy in ACS

The technical advances in PCI in the setting of ACS have relegated CABG largely to a secondary position in most cases. The special circumstances of postinfarction mechanical complications of papillary muscle rupture, ventricular septal defect, and shock are addressed specifically in other chapters of this text. It should be noted here, however, that two multicenter trials and one single-center randomized trial involving a total of 823 patients have evaluated the relative merits of CABG surgery and medical therapy in unstable angina, excluding left main disease, poor left ventricular function (ejection fraction <30%), and age greater than 70 years during the 1970s.79–81 The VA cooperative study demonstrated improved survival and a lower rate of recurrent angina with surgery, and at both 5 and 8 years there were fewer subsequent hospitalizations for cardiac reasons in the surgical group.79 Interestingly, there was no difference in progression to Q wave MI between medical and surgical groups. Like the VA study, the National Cooperative Study Group Trial80 showed no difference in progression to Q wave MI, but less severe subsequent angina with operation. Unlike the VA trial, however, there was no survival difference at 2 years (90% in both groups). Of note, 32% of the medical group crossed over to surgery by 24 months. As current medical therapy was not available to these patients, there is significant difficulty in extrapolating the results of these trials to current clinical practice. Finally, Bertolasi and colleagues reported a single-center study of 113 patients, which demonstrated less subsequent angina, fewer infarctions, and a survival benefit for surgery in short-term follow-up.81

In the TIMI-IIIB trial of medical management followed by early PCI or CABG, 6-week mortality and nonfatal MI rates were 2.1 and 6.1% among 1473 patients with unstable angina or non–Q wave MI (NQWMI).82 This study compared the results of a strategy of initial stabilization followed by aggressive treatment involving routine angiography followed by revascularization in the presence of suitable anatomy with a conservative arm reserving angiography for those with recurrent angina or a positive stress test. At 42 days and 1 year follow-up there was no difference in death or MI between the two groups. Subsequent subset analyses have demonstrated a trend in favor of an aggressive approach to revascularization over medical therapy in patients at higher risk as characterized by an elevated CPK-MB fraction (NQWMI).82 In the end, revascularization rates were similar, with only the timing of that revascularization event being different.

The Veterans Affairs non–Q wave infarcts and strategies in hospitals (VANQUISH) trial83 was a similar design to TIMI-IIIB. A higher early mortality rate was observed in the invasive group than in the medical group, possibly because of the extraordinarily high perioperative mortality rate of 7.7% in the CABG group. The opposite result was found in the second Fragmin and Fast Revascularization during Instability in Coronary Artery Disease trial (FRISC II).76 These investigators found a benefit with early revascularization, particularly among patients with elevated troponins. The reason for such different results among these studies is likely owing to differences in patient populations studied. It is likely that higher-risk patients benefit from an aggressive approach, whereas lower-risk patients have less to gain and so are more likely to suffer adverse consequences.

The Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) trial was reported in 2004,84 comparing results from PCI and CABG among patients with more than one of the following risk factors: prior CABG; ACS within 7 days; LVEF less than 35%; age greater than 70 years; or intra-aortic balloon pump. The results suggested that PCI and CABG have similar outcomes for acute coronary syndromes in these patients even in the presence of low ejection fractions.

PCI for Acute MI

Because of the rapidity with which vessel patency can be restored using percutaneous techniques, PCI has all but replaced CABG in the setting of acute ST elevation MI (STEMI). Both thrombolytic therapy and direct or primary angioplasty can restore coronary artery patency and flow during acute STEMI. In the absence of hemorrhagic concerns, however, thrombolytic therapy is more widely available and is standard early therapy for acute transmural MI when immediate angioplasty is unavailable.

In the few instances in which surgical revascularization must be undertaken following thrombolysis or acute angioplasty, perioperative bleeding is increased. Bleeding has been shown not to be excessive if glycoprotein IIb/IIa inhibitors are discontinued at least 2 hours preoperatively85 or if a platelet transfusion is provided in the presence of abciximab.86 Clopidogrel should be held for 5 days before surgery if possible.87

Several early myocardial reperfusion trials have assessed the role of routine adjunctive angioplasty given that not all arteries can be reopened by thrombolysis, reocclusion occurs in some arteries initially opened, and reocclusion is associated with increased morbidity and mortality.88,89 In these studies, the addition of routine angioplasty to thrombolytic therapy did not enhance patency, improve left ventricular function, or reduce early mortality in comparison with a more conservative approach of ischemia-driven angiography, but did increase expense and vascular bleeding problems.90,91 A meta-analysis of adjunctive PCI and thrombolysis versus thrombolysis only showed no early benefit of PCI except in patients who have clinical indications for early revascularization (eg, postinfarction angina).92 These studies were performed in an early phase of PCI, however, and the addition of stents as well as IIb/IIIa inhibitors and new lytics have more recently renewed interest in a combined strategy.

Asymptomatic Coronary Artery Disease

The role of revascularization either by PCI or CABG versus medical therapy in the setting of asymptomatic coronary artery disease has been studied in the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial.93 Of 558 patients with coronary artery disease and medically controlled angina, treatment was randomized to either revascularization or medical therapy directed toward eliminating angina or eliminating ischemia during ambulatory ECG. Revascularization was more effective than medical therapy in relieving ischemia, and CABG was superior to PCI (70% freedom from ischemia versus 46%, p < .002). Mortality at 1 and 2 years was superior for revascularization as compared with angina-directed medical therapy, but not superior to ischemia directed medical therapy.29,93 The greatest benefit was among those patients with the most severe disease. Importantly, many of these patients with “silent ischemia” on ambulatory ECG monitoring did have symptomatic angina at other times and thus were not truly asymptomatic.

The documentation of ischemia, however, is critical. Several studies emphasize the flaws in the assumption that one can identify future culprit lesions in the absence of symptoms or documentation of ischemia. Among patients undergoing serial coronary arteriography who subsequently developed acute MI or unstable angina, the severity of stenosis at the time of initial angiogram is poorly predictive of the culprit lesion causing the acute ischemic syndrome.94,95 In most cases the severity of the lesion responsible for subsequent ischemia was less than 50%, and in many patients it was not present at all on the initial angiogram, raising concern regarding the number of asymptomatic or minimally symptomatic patients undergoing angioplasty without stress testing.96 Bech and associates have demonstrated that fractional flow reserve exceeded 0.75 in 91 of 325 patients planned for PCI without noninvasive evaluation of ischemia, and that among those patients, angioplasty had no impact on event-free survival or angina.97

Drug-Eluting Stents

Recent progress in stent technology, particularly the introduction of drug-eluting stents (DESs), promises to further reduce the incidence of restenosis. The use of stents has reduced adverse remodeling, and stents eluting medications such as sirolimus or paclitaxel, are having a profound effect on the patterns of interventions for CAD. When compared with bare-metal stents, DESs have not been shown to convey any advantage in terms of MI or mortality, but do demonstrate decreased rates of angiographic restenosis in a meta-analysis of 11 randomized trials.98 In an observational study of 1680 patients who had CABG or PCI with a DES, CABG provided a benefit in terms of major cardiac events for patients with two- or three-vessel disease, as well as diabetic patients.99 In another cohort of patients with multivessel disease, CABG was associated with lower rates of death, myocardial infarction, and target-vessel revascularization than drug-eluting stents. Thus, although DES may have some advantage over bare-metal stents, the indications for PCI and CABG have not changed.100

Left Main Disease

Significant left main disease has been considered an indication for CABG rather than PCI for many years, but recently studies have begun to question this. In a matched cohort of more than 1100 patients with unprotected left main disease, there was no difference in the rates of death or the composite outcome of death, Q wave myocardial infarction, or stroke between patients undergoing CABG or PCI despite a greater rate of target-vessel revascularization in the PCI group, including the patients who received DES.101 Another single-center observational study focused on octogenarians reported no significant differences in cardiac death, myocardial infarction, or major adverse cardiac events between CABG and PCI at a mean follow-up of 2 years.102 Recently, a randomized study enrolled 105 patients with unprotected left main coronary artery disease. The study had the unusual primary end point of the change in left ventricular ejection fraction after 1 year. The authors found that there was a significant increase in ejection fraction only in the PCI group (3.3%) compared with the CABG group (0.5%). There was no difference in survival at 1 year or in major cardiac adverse events. However, it should be noted that of the patients who received CABG, only 72% received a LIMA graft, which would generally not be reflective of current surgical practice.

Severe Left Ventricular Dysfunction

Left ventricular dysfunction is a predictor of increased operative risk for most cardiac surgical procedures, and in the early days of coronary revascularization these patients were not offered CABG. Like age, however, it is also a strong predictor of poor outcome with medical therapy. Accordingly, more recently significant LV dysfunction has been considered an indication rather than contraindication to surgical revascularization. In some patients, LV function has been shown to improve—sometimes dramatically so—after revascularization, leading to the concept of “hibernating” or “stunned” myocardium.103–105 The identification of viable myocardium, which is potentially recoverable, depends on the identification of preserved metabolic activity by positron emission tomography (PET), cell membrane integrity by thallium-201 or technetium-99m SPECT, or dobutamine stress echocardiography.106

The only randomized trial in patients with severe LV dysfunction, the Surgical Treatment for Ischemic Heart Failure (STICH) trial, compared medical versus surgical therapy. The results from this hypothesis have not yet been published. However, a number of retrospective analyses of the impact of revascularization on outcome in patients with LV dysfunction with or without demonstrable viability have been reported (Fig. 19-9).107 Allman and colleagues reported the results of a meta-analysis of these studies108 demonstrating a 79.6% reduction in annual mortality (16% versus 3.2%, p < .0001) among patients with severe three-vessel disease, severely depressed LV function, and evidence of viability undergoing surgery versus medical therapy. Among those patients without demonstrable viability, the mortality rates were similar (7.7% versus 6.2%, p = NS). This study is subject to all of the limitations of a retrospective surgical series, however, including perhaps most importantly the unaccountable effect of clinical judgment employed in selecting patients for one therapy versus another.

The relative roles of CABG and PCI in this population are not clearly defined despite the number of randomized trials of angioplasty versus surgery, largely because these patients were excluded from trial entry. In a multicenter study of patients with left ventricular dysfunction (ejection fraction <40%), slightly more than one-fourth of the patients were dead in the 2 years following multivessel angioplasty.109 Similar results have been reported from other studies of PCI in patients with multivessel disease and left ventricular dysfunction. Overall, the outcome with PCI appears less favorable than that obtained after CABG surgery,32 possibly as a function of more complete revascularization in surgical patients.110

Completeness of revascularization may be particularly important in patients with left ventricular dysfunction. An analysis of data from the CASS registry demonstrated that, among patients with triple-vessel disease, 4-year survival was dependent on the number of vessels bypassed, particularly among those with more severe angina and those with worse ventricular function.110 For PCI, complete of revascularization of target arteries ranged from 57 to 61% in the prospective randomized trials in which complete revascularization was not a protocol requirement (BARI, EAST, CABRI). In the GABI and RITA trials complete revascularization by PCI was targeted and was achieved in 86% in GABI and in 81 and 63% of patients with two- or three-vessel disease in RITA.59,60

Total Occlusion

In most patients with chronic, totally occluded coronary arteries, revascularization is not possible, although the advent of stent technology has offered some improvement in this area. In the randomized trials of multivessel PCI versus CABG, 35 to 37% of the patients excluded were disqualified because of the presence of a chronic total occlusion of a coronary artery serving viable myocardium. Thus the high proportion of trial patients with less than three-vessel disease, well-preserved ventricular function, and absence of chronically occluded arteries produces a study population that favors a higher incidence of complete revascularization by PCI and attenuated consequences of incomplete revascularization than expected in community practices. Among patients with severe angina, triple-vessel disease, and ventricular dysfunction, survival is greater in those with three or more coronary arteries bypassed than in those with only two vessels bypassed.24,109 CABG surgery improves survival in patients with three- and two-vessel disease with left ventricular dysfunction compared with medical therapy. Although angioplasty may have a similar survival benefit, its influence on this high-risk subgroup has not been fully tested or reported.

The Elderly

Age is a predictor of operative risk in most models, but is also a predictor of poor outcome with medical therapy in the presence of coronary artery disease. The Swiss Multicenter Trial of invasive versus medical therapy in the elderly (TIME) trial briefly noted in the preceding, examined 301 patients greater the age of 75 with chronic angina were randomized to medical therapy with or without invasive evaluation.31 Of those undergoing angiography, two-thirds had revascularization. At the 1-year follow-up interval, there was no statistical difference in death or nonfatal myocardial infarction rates. Symptoms and quality of life were also similar. However, there was a substantial increased risk of rehospitalization with revascularization in those who had medical treatment. These data suggest that invasive evaluation should be offered to elderly people who are symptomatic only after adequate medical therapy.

The choice of mode of revascularization will be particularly impacted in this group of patients by the presence of comorbidities that may increase the risk of surgical intervention, such as cerebrovascular disease, renal dysfunction, and pulmonary disease. The impact of a reduction in operative morbidity through “off-pump” coronary bypass (OPCAB) on this choice is as yet unclear. There are an increasing number of studies to suggest that it is in just this group of patients with comorbid conditions that “off-pump” surgery offers its greatest advantage over conventional surgery. The majority of these studies are not randomized, however, making their results less conclusive than one would hope. There are two retrospective and nonrandomized trials reviewing elderly patients who underwent OPCAB. There were more grafts in the standard CABG for both studies, but there were fewer strokes, incidences of prolonged respiratory failure, bleeding, transfusions in the OPCAB group, and both ICU and hospital length of stay were reduced. Reoperation for bleeding, MI, renal failure, wound infections, and operative mortality were not significantly different.111,112 Among the randomized trials, there has been no consistent advantage to OPCAB with respect to neurocognitive outcomes, a particularly important end point in elderly people.113 A meta-analysis of both randomized and observational studies of OPCAB and standard “on-pump” CABG in diverse populations113,114 has failed to demonstrate any difference except for a reduction in atrial fibrillation in the OPCAB group (OR 0.59 [0.46–0.77]). The impact, therefore, of newer technologies on modifying the indications for CABG in elderly people is as yet unclear.

Diabetes Mellitus

It has been recognized for many years that patients with diabetes mellitus are at higher risk following percutaneous115,116 or surgical117 revascularization. The BARI trial was the first trial large enough to identify significant differences in outcome between diabetic and nondiabetic patients. In this study, which included 353 diabetic patients, a survival benefit was observed among insulin-dependent patients undergoing CABG with an ITA, as compared with those undergoing PCI. The explanation for this is not entirely clear, although an intriguing observation is that while the incidence of subsequent MI is similar between groups, survival after MI is superior among those who have undergone surgical revascularization.118 In fact, diabetics suffering spontaneous Q wave MI were more than 10 times as likely to die with their infarction if they had been treated with PCI as compared with CABG. No such protective effect was seen among nondiabetic patients either with or without Q wave MI. This survival difference was even more pronounced at 7 years with 76.4% of diabetics in the surgical arm alive as compared with 55.7% in the angioplasty arm.119

The physiologic basis for this difference remains a matter of speculation, although the completeness of revascularization may be a factor. Because of the significant incidence of restenosis after PCI in diabetics, Van Belle and colleagues120 analyzed ejection fraction at 6 months and long-term cardiac mortality and morbidity among 513 diabetic patients stratified according to the presence of occlusive restenosis (n = 94), nonocclusive restenosis (n = 257), and no restenosis (n = 162). The mortality rose with restenosis (24% without restenosis, 35% with nonocclusive restenosis, and 59% with occlusion), and ejection fraction fell with occlusion (decrease of 4.8% ± 12.6%). Coronary occlusion was strongly predicted by coronary occlusion by multivariate analysis.

The results of the BARI trial prompted retrospective post hoc analyses of several earlier trials. The results have been variable. An analysis of diabetic patients from the CABRI trial at 8 years demonstrated a mortality rate of 3.5% for CABG patients versus 15.6% for PCI.121 There was also a nonsignificant trend for better survival among diabetic patients treated surgically in the EAST trial.122 A meta-analysis of pooled data pertaining to diabetic patients from CABRI, EAST, and RITA, however, found similar 5-year mortality rates following CABG or PCI.123

The follow-up study to BARI, BARI-2D, has recently been reported.124 A total of 2368 patients with diabetes mellitus and stable coronary artery disease were randomized to receive either intensive medical therapy or intensive medical therapy and prompt revascularization (CABG or PCI left to clinical judgment). At 5 years there was no different in survival or freedom from major cardiovascular events (myocardial infarction or stroke) between medical therapy and revascularization groups. This trial was not designed to compare CABG and PCI in diabetes, but rather to examine a strategy of intensive medical therapy compared with revascularization. However, in the stratum of patients who received CABG, there were fewer major cardiovascular events when compared with medical therapy (22.4 versus 30.5%, p = .002). In the stratum of patients who received PCI, there was no difference in major cardiovascular events when compared with medical therapy.

Several other data bank studies have also been conducted. The Northern New England Cardiovascular Disease Study Group evaluated survival 5 years after treatment among 7159 diabetic patients with multivessel disease who were treated with CABG or PCI between 1992 and 1996.125 Of this group, 38.6% of patients were clinically and angiographically similar to those randomized in BARI. Patients were treated according to physician preference. Those undergoing CABG were more likely to have three-vessel disease and tended to be older with greater degrees of ventricular impairment and obstructive lung disease. There were more women and more urgent interventions in the PCI group. After adjusting for these variables, PCI was associated with a significantly greater mortality rate at 5 years (risk ratio 1.49, 95% confidence interval 1.02 to 2.17, p = .037) and particularly among diabetics with three-vessel disease (hazard ratio 2.01, confidence interval 1.04 to 3.91, p = .038).

Diabetes is a condition characterized biologically by an inflammatory, proliferative, and prothrombotic state. This may account in part for the increased risk of restenosis and occlusion. Because diabetics tend to have more diffuse disease, the importance of complete revascularization, which is more often achieved surgically that percutaneously, may be enhanced. Another explanation may have more to do with patient selection than vascular biology. It has long been recognized from the previously cited studies that the survival advantage of CABG over medical therapy is greater the more extensive the coronary disease; and more recent studies of PCI versus CABG have demonstrated similar trends. Diabetic patients tend to have more extensive disease, and in BARI diabetics had a higher frequency of three-vessel disease, diffuse disease, proximal LAD disease, and left ventricular dysfunction.

In this respect, it is interesting to note that in community studies126 and the BARI Registry, although diabetics have a poorer outcome with both PCI and CABG in comparison with nondiabetics, there were no significant differences in outcomes between these therapies in the diabetic subgroup. It must be emphasized that in these nonrandomized trials in which the selection of therapy was at the discretion of the physician and the patient, a very clear trend was noted. The “sicker” patients with left ventricular dysfunction and triple-vessel disease were far more likely to undergo CABG in contrast with patients with double-vessel disease and preserved left ventricular function. Therefore, these registry studies suggest that although the differences between bypass surgery and PCI in diabetics may be caused by altered vascular biology, these differences are magnified by the process of randomization in which patients who probably would have been treated with CABG in clinical practice were randomized to PCI.

From a clinical standpoint in regard to patient selection for coronary revascularization and the method of revascularization, the assessment of diabetics should be made on standard principles, namely, the severity and extent of coronary disease, the potential for complete revascularization, the presence or absence of left ventricular dysfunction, and the technical suitability of the lesions for PCI. The results of the aforementioned studies suggest that a preference for surgical over percutaneous revascularization is, at this time, appropriate among diabetics—at least those with extensive disease and/or ventricular dysfunction. This recommendation may change if new technologies such as drug-eluting stents and antiplatelet agents are successful in reducing the risk of restenosis and occlusion. DES are being used with greater frequency due to subset analysis of the TAXUS IV and SIRIUS trials showing a significant decrease in restenosis. However, these studies were not powered to determine restenosis rates in diabetics and there is significant risk of a type I error.127–129 Furthermore, the potential impact of risk factor reduction may alter the risk:benefit balance in future in this important and increasing subset of patients presenting with coronary artery disease. Current data suggest that the decreased incidence of repeat revascularization, cardiac rehospitilization, and recurrent angina can be reduced to the level of nondiabetics if diabetics maintain optimal glycemic control (HbA1c ≤ 7%).130 Irrespective of the mode of therapy, an aggressive approach to risk factor modification is required.

End-Stage Renal Disease

End-stage renal disease (ESRD) is a growing problem. Cardiovascular disease is the most common cause of death among those with ESRD; therefore, there will likely be high rates of revascularization required in these patients in the future. Comorbidities complicating surgical or percutaneous revascularization, such as diabetes, hypertension, and calcified vessels, are more common in patients with ESRD, increasing the risk of intervention. A study conducted by the Northern New England Consortium found dialysis-dependent patients with renal failure to be 3.1 times more likely to die after CABG after adjusting for known risk factors (OR 3.1, [2.1 to 3.7], p < .001).131 They also found significantly increased rates of mediastinitis (3.6% versus 1.2%) as well as postoperative stroke (4.3% versus 1.7%).157 The long-term survival was also decreased with renal failure, which was found to be a highly significant predictor of mortality after adjustment.132 Despite these risks, the prognosis without surgical correction of coronary artery disease is poor. Revascularization in patients with ESRD is associated with improved survival compared with medical management.133