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J Am Coll Cardiol, 1999; 34:1262-1347 © 1999 by the American College of Cardiology Foundation |
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Table of Contents |
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 Top Table of Contents PreambleI. IntroductionII. General considerations and...III. OutcomesIV. Management strategiesV. Special patient subsetsVI. Impact of evolving...VII. Institutional and operator...VIII. Economic issuesIX. IndicationsX. Areas in need...StaffSubject indexReferences |
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Preamble |
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TopTable of ContentsPreambleI. IntroductionII. General considerations and...III. OutcomesIV. Management strategiesV. Special patient subsetsVI. Impact of evolving...VII. Institutional and operator...VIII. Economic issuesIX. IndicationsX. Areas in need...StaffSubject indexReferences |
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The American College of Cardiology (ACC) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. This effort is directed by the ACC/AHA Task Force on Practice Guidelines, whose charge is to develop and revise practice guidelines for important cardiovascular diseases and procedures. Experts in the subject under consideration are selected from both organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups where appropriate. Writing groups are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes when data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered, as well as frequency of follow-up and cost-effectiveness.
The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual or potential conflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing panel. Specifically, all members of the writing panel are asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. These statements are reviewed by the parent task force, reported orally to all members of the writing panel at the first meeting, and updated yearly and as changes occur.
These practice guidelines are intended to assist physicians in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the physician and patient in light of all of the circumstances presented by that patient.
The executive summary and recommendations are published in the September 28, 1999, issue of Circulation. The full text is published in the October 1999 issue of the Journal of the American College of Cardiology. Reprints of the full text and the executive summary are available from both organizations.
Raymond J. Gibbons, MD, FACC
Chair, ACC/AHA Task Force on Practice Guidelines
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I. Introduction |
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TopTable of ContentsPreambleI. IntroductionII. General considerations and...III. OutcomesIV. Management strategiesV. Special patient subsetsVI. Impact of evolving...VII. Institutional and operator...VIII. Economic issuesIX. IndicationsX. Areas in need...StaffSubject indexReferences |
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The current Committee was charged with revising the guidelines published in 1991 (1). The Committee reviewed pertinent publications, including abstracts, through a computerized search of the English literature since 1989 and performed a manual search of final articles. Special attention was devoted to identification of randomized trials published since the original document. A complete listing of all publications covering coronary bypass surgery in the past 10 years is beyond the scope of this document. However, evidence tables were developed and extensively reviewed by an expert in meta-analysis. Inaccuracies or inconsistencies present in the original publication were identified and corrected when possible. Recommendations provided in this document are based primarily on published data. Because recent randomized trials are unavailable in many facets of coronary artery disease (CAD) treatment, observational studies and, in some areas, expert opinion form the basis for recommendations that are offered. In each section of the Indications (Section IX), the relative levels of evidence favoring the Class I, II, and III indications were noted.
The ACC/AHA classifications I, II, and III are used to summarize indications as follows:
Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective.
Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/or efficacy of a procedure.
Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.
Class IIb: Usefulness/efficacy is less well established by evidence/opinion.
Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful.
The Committee consists of acknowledged experts in cardiac surgery, interventional cardiology, general cardiology, internal medicine, and family practice. The Committee included representatives from the American Academy of Family Physicians (AAFP) and the American College of Physicians (ACP), as well as the Society for Thoracic Surgery (STS). Both academic and private practice sectors were represented. The document was reviewed by 3 outside observers nominated by the ACC and 3 outside reviewers nominated by the AHA, as well as outside reviewers nominated by AAFP, ACP, STS, the American College of Surgery, and the Society of Cardiovascular Anesthesiologists. This document will be reviewed annually after publication by the Task Force to determine whether a revision is necessary. The guidelines will be considered current unless the Task Force revises them or withdraws them from distribution.
These guidelines overlap several previously published ACC/AHA guidelines, including those for the management of acute myocardial infarction (MI), for the management of stable angina, for percutaneous transluminal coronary angioplasty (PTCA), and for exercise testing. For each of these guidelines, an analysis of overlap or contradiction has been explored by the Committee with attempts to create consensus in each instance. Finally, it is acknowledged that no guideline can take into account all of the various parameters that must be part of the individual decision to recommend CABG for a single patient. However, this entire report is intended to provide a framework that doctors can use in combination with other types of knowledge and patient preferences to make rational decisions about treatment.
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II. General considerations and background |
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TopTable of ContentsPreambleI. IntroductionII. General considerations and...III. OutcomesIV. Management strategiesV. Special patient subsetsVI. Impact of evolving...VII. Institutional and operator...VIII. Economic issuesIX. IndicationsX. Areas in need...StaffSubject indexReferences |
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Alexis Carrel (1872 to 1944) understood the association between angina pectoris and coronary stenosis (2). Before World War I, he had developed a canine model of aortocoronary anastomosis using carotid arteries as a conduit. For his seminal work in the development of cardiovascular surgical techniques, he was awarded the Nobel Prize. Carrel’s contributions lay fallow, as he had predicted, until a time when advances in technology would allow safe application to humans.
Carrel and the aviator Charles Lindbergh collaborated in the 1930s in developing a primitive heart-lung machine intended to allow direct cardiac operation. Lindbergh was driven to this project by the desire to save a family member dying of valvular heart disease. The project did not produce a clinically useful device, but it did make incremental progress toward the ultimate goal (3). Over a professional lifetime of intense dedication, John Gibbon developed a clinically useful cardiopulmonary bypass (CPB) technology and applied it successfully to a patient in 1953 (4).
With direct coronary operation awaiting advancing techniques, surgical efforts to relieve angina pectoris in the mid-20th century included suppression of metabolic stimulation through thyroidectomy and augmentation of noncoronary flow to the myocardium through creation of pericardial or omental adhesions. Attempts to create an artificial collateral by implantation of the internal mammary artery (IMA) into the myocardium, the Vineberg procedure, met with limited success (5).
Coronary surgery moved into the modern era in the 1950s. It is not entirely clear to whom credit should be given for the first coronary bypass. The first direct surgical approach to the coronary circulation in a patient was likely performed by William Mustard in 1953 in Toronto, who used a carotid-to-coronary bypass. The patient did not survive the operation.
The first clinical use of the IMA to graft a coronary vessel appears to have been in response to an intraoperative misadventure. William Longmire applied the technique of coronary endarterectomy in a series of patients in 1958. A right coronary artery disintegrated during one of these operations, and an IMA was placed as a direct graft to restore flow. In retrospect, the surgeon thought it to be a good operation (2).
Michael DeBakey and Edward Garrett had a similar experience with a left anterior descending (LAD) coronary endarterectomy in 1964 (6). This situation was salvaged by an aortocoronary saphenous vein graft (SVG). The patient did well and had a patent aortocoronary SVG when restudied 8 years later. This experience was subsequently recorded and recognized as the first successful clinical aortocoronary SVG. An aortocoronary SVG operation by David Sabiston at Duke in 1962, involving an anastomotic end-to-end technique done without the use of CPB, was the first planned saphenous vein operation but was complicated by an early fatal outcome (7,8).
Mason Sones showed the feasibility of selective coronary arteriography and amassed a large library of cineangiograms that were studied in depth by Rene Favaloro (9). Sones and Favaloro formed an innovative team that demonstrated the efficacy and safety of SVG interposition and aortocoronary SVGs for single-vessel, left main, and multivessel coronary disease. An explosive growth in the application of these techniques ensued, such that within a decade, coronary bypass operation became the most frequent surgical procedure in the United States.
Recognition of the value of the IMA (also known as the internal thoracic artery) as a conduit came slowly. V.I. Kolessov, working in the 1960s at the Pavlov Institute in Leningrad, described a series of patients in whom the IMA was used for coronary revascularization without the aid of routine arteriography or CPB (10,11). Frank Spencer developed extensive experimental experience with the IMA to the coronary circulation in canine models. After preliminary animal and cadaveric work with microscopic methods, George Green brought this technique to successful clinical application. Floyd Loop and colleagues at the Cleveland Clinic incorporated the IMA into the coronary operation in a large series of patients and subsequently published the landmark article demonstrating the powerful survival benefit afforded by use of the IMA for LAD coronary distribution revascularization (12).
The 1970s, the first full decade of CABG, helped to define its appropriate role relative to medical therapy. Coronary bypass was found to consistently relieve angina and improve the quality of life in symptomatic patients. Three large, prospectively randomized, multicenter trials, The Coronary Artery Surgery Study (CASS), The Veteran’s Administration Coronary Artery Bypass Trial, and the European Coronary Artery Bypass Trial, were conducted. These trials and several smaller studies helped to define subsets of patients likely to benefit from coronary bypass surgery in terms of prolongation of life and specifically identified patients with more advanced disease as those most appropriate for application of the operation for survival benefit. In addition to patients with triple-vessel disease and left main disease, patients with ischemic left ventricular (LV) dysfunction were found to benefit from the operation relative to medical therapy. These results led to the application of coronary bypass to progressively sicker patients in the 1980s.
Improvements in operative techniques and new technologies have allowed increasingly difficult patients to be approached with success. Improvements in cardiac anesthesia have paralleled improvements in operative techniques. Operation on complex patients became routine as sophisticated perioperative monitoring techniques, such as Swan-Ganz pulmonary artery catheters and intraoperative transesophageal echocardiography (TEE), were applied to specific problem situations. Anesthetic techniques, CPB technology, and most important, methods of myocardial protection were refined and successfully applied to specific problem situations. Close collaboration between the surgeon, the anesthesiologist, the perfusionist, and the intensive care team has been critically important to these advances. These refinements, discussed in Section VI, have led to an expected 30-day mortality of <1% in patients receiving elective coronary bypass who are <65 years of age and who have no severe LV dysfunction or congestive heart failure (CHF). Even in otherwise uncomplicated patients aged <65 years and with an ejection fraction (EF) of 0.25 to 0.35, first-time coronary bypass has an operative risk of <5%.
In addition to improvements in short-term outcomes, evolving technology has contributed to improved long-term results. The widespread use of the IMA, the use of other arterial conduits, long-term antiplatelet therapy, and lipid management are discussed in later sections of these guidelines. Progress has also been significant in the moderation of perioperative morbidity. Central nervous system (CNS) injury, the systemic insults of CPB, infection, and bleeding are addressed in subsequent discussions. Finally, the application of CABG without CPB and through limited incisions has recently presented the prospect of further reductions in perioperative morbidity.
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III. Outcomes |
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TopTable of ContentsPreambleI. IntroductionII. General considerations and...III. OutcomesIV. Management strategiesV. Special patient subsetsVI. Impact of evolving...VII. Institutional and operator...VIII. Economic issuesIX. IndicationsX. Areas in need...StaffSubject indexReferences |
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2. Predicting hospital mortality
The risk of death with CABG has been the focus of numerous studies in the last 2 decades. Although early reports were useful in correlating patient factors with outcomes such as in-hospital mortality (13), they were inadequate in their ability to risk stratify (14,15). Subsequently, a number of large single-center and multicenter cardiac surgical databases were established (13,16,17). From these databases, risk stratification models were created to better understand the variation in institutional and surgeon performance and to provide a more accurate risk prediction of mortality for patients facing CABG. Although all datasets identified patient and disease characteristics that consistently predicted mortality, the inclusion or exclusion of certain variables, variations in definitions of the same variables, and institutional and regional differences in practice styles have made it difficult to compare results across datasets. A review of 7 large datasets, representing >172,000 patients who underwent surgery between 1986 and 1994, was carried out to find the predictive power of certain preoperative variables (18). Seven core variables (ie, urgency of operation, age, prior heart surgery, sex, LVEF, percent stenosis of the left main coronary artery, and number of major coronary arteries with >70% stenosis) were found to be predictive of mortality after CABG in all 7 datasets. Variables relating to the urgency of operation, age, and prior coronary bypass surgery were found to have the greatest predictive power, while variables describing coronary anatomy had the least predictive power. Besides these 7 core variables, 13 "level 1" variables were identified that, when added to the core variables, had a modest influence on the predictive capability of the model. These level 1 variables included the following: PTCA during index admission; recent (<1 week) MI; history of angina, ventricular arrhythmia, CHF, or mitral regurgitation (MR); comorbidities including diabetes, cerebrovascular disease, peripheral vascular disease (PVD), chronic obstructive pulmonary disease (COPD), and creatinine level. While the level 1 variables carry predictive power, their addition beyond these 7 core variables has been found to have a minimal impact on predictability (15).
While Jones and others have attempted to develop a common risk stratification language, general application of risk stratification models across populations must be done with caution. Although it may be possible to generalize the relative contribution of individual patient variables, rules must be calibrated to regional mortality rates and should be updated periodically to maximize accuracy (19,20). Table 1 compares the relative risk of the 7 core variables identified by Jones et al (18) to be most predictive of mortality as reported by 6 datasets.
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Sex also predicts early mortality after CABG, with females facing an increased risk. Reported relative risks have ranged from 1.5 to 2.0. Smaller body size (30), smaller diameter of coronary arteries (31), increased age, and comorbidity status (32) have all been suggested as explanations for this increased risk. Despite the increased risk, long-term results appear similar to those of males (33).
Having had previous open heart surgery adds considerable risk for patients having subsequent coronary artery surgery. The relative risk of early mortality appears to be 
3.0 compared with first-time CABG patients (16). An additional factor that further increases risk in this subset appears to be whether reoperation is carried out within 1 year of the primary operation (34). Despite the significant increased risk, long-term results after reoperative CABG are encouraging (35).
Coronary artery surgery in the presence of or immediately after an acute MI is controversial. Despite optimistic reports of low mortality if the operation is carried out within 6 hours of the onset of chest pain (36), most authors have found this approach to carry excessive mortality (37–39). Fibrinolytic therapy and/or PTCA appears to be the preferable first-line therapy in the presence of an evolving MI. CABG surgery is reserved for patients with evidence of ongoing ischemia despite these interventions, or it may be performed coincident with repair directed at mechanical complications of infarction (ie, ventricular septal defect or papillary muscle rupture).
The presence of comorbidities is also related to survival after CABG. Though not identified by Jones et al (18) as a core variable, treated diabetes (40), the presence of PVD (41), renal insufficiency (42), and COPD have all been shown to have a negative impact on outcome after CABG.
A nonoperative variable that seems to have both a short-term and a long-term impact on survival is the use of the IMA as a bypass conduit. Loop, Lytle, and others have reported that use of the IMA is an independent predictor of survival 10 to 20 years after CABG (43,44). Hospital mortality after CABG has also been reported to be lower when the IMA is used (45).
In summary, early mortality after CABG is associated particularly with advancing age, poor LV function, and the urgency of operation. Additional coronary anatomic and comorbid conditions further influence risk. If overall risk for an institution or region is known, then a general estimate for the individual patient can be rendered preoperatively by using mathematical models, as illustrated in Table 2 and Figure 1. This application may find utility as patients and their physicians weigh the potential benefits versus risks of proceeding with bypass surgery.
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Postoperative neurological deficits have been divided into 2 types: type 1 deficits are those associated with major, focal neurological deficits, stupor, and coma; type 2 deficits are characterized by deterioration in intellectual function or memory. Roach et al (51) reported on a multi-institutional prospective study aimed at determining the true incidence of both stroke (type 1 deficits) and encephalopathy (type 2 deficits) after CABG. In this study, 2108 patients operated on at 24 institutions were observed for signs of neurological dysfunction after CABG. Adverse cerebral outcomes occurred in 129 patients (6.1%) and were evenly distributed between type 1 (3.1%) and type 2 (3.0%) deficits. The influence of these complications included a 21% mortality for those with type 1 deficits and a 10% mortality for those with type 2 deficits. In addition, patients with neurological complications had, on average, a 2-fold increase in hospital length of stay and a 6-fold likelihood of discharge to a nursing home.
Independent risk factors were identified for both type 1 and type 2 deficits (51). Predictors of both types of cerebral complications included advanced age, especially age >70 years, and a history or the presence of significant hypertension. Both of these variables have previously been reported to be associated with adverse cerebral outcomes after CABG (28,52).
Predictors of type 1 deficits included the presence of proximal aortic atherosclerosis as defined by the surgeon at the time of surgery (odds ratio [OR] 4.52), a history of prior neurological disease (OR 3.19), use of the intra-aortic balloon pump ([IABP] OR 2.60), diabetes (OR 2.59), a history of hypertension (OR 2.31), a history of unstable angina (OR 1.83), and increasing age (OR 1.75 per decade). Perioperative hypotension and the use of ventricular venting were also weakly associated with this type of outcome.
Proximal aortic atherosclerosis has been reported to be the strongest predictor of stroke after CABG, supporting the theory that liberation of atheromatous material during manipulation of the aorta is the main cause of this complication (53). Although palpation of the aorta has traditionally been used by surgeons to identify patients with atheromatous disease of the ascending aorta and to find "soft spots" for cannulation or cross clamping, the use of ultrasound has been suggested as a more accurate means of assessing the aorta (54). Duda et al (54) have suggested that once aortic atherosclerosis is identified, alternative strategies to prevent mobilization of aortic atheroma should be considered, including techniques such as groin or subclavian placement of the aortic cannulas, fibrillatory arrest without aortic cross-clamping, use of a single cross-clamp technique, modifying the placement of proximal anastomoses, or all-arterial revascularization. Other authors recommended ascending aortic replacement under circulatory arrest as the best means of minimizing this complication (55,56).
A history of previous neurological abnormality or the presence of diabetes is also a predictor of type 1 CNS complications. These are likely markers for patients with marginal cerebral blood flow, alterations in CNS vasomotor autoregulatory mechanisms, or diffuse atherosclerosis. The need for an IABP is likely correlated with a higher risk of atheromatous emboli and is often required in patients with systemic hypoperfusion, each of which may cause stroke after CABG. The fact that use of an LV vent has been associated with stroke suggests air emboli as the cause and argues for meticulous technique when placing these devices to prevent this complication.
Factors predictive of type 2 neurological deficits include a history of alcohol consumption, dysrhythmia (including atrial fibrillation), hypertension, prior CABG, PVD, or CHF. Because aortic atherosclerosis is not a predictor of type 2 complications, encephalopathic changes may be related to the brain’s microcirculation and are more likely to occur after periods of hypotension or inadequate perfusion.
Individual patient counseling regarding postoperative stroke risk represents an important opportunity to assist patients as they weigh the risks and benefits of elective CABG. Although postoperative stroke rates may vary between hospitals or regions, if local rates are known, then these may be used to assist the patient in appreciating the general risk of this dreaded complication. Strategies to reduce the risk of postoperative neurological complications are discussed in depth in Section IV, A1.
4. Morbidity associated with CABG: mediastinitis
Deep sternal wound infection has been reported to occur in 1% to 4% of patients after CABG and carries a mortality rate of nearly 25% (57,58). Studies have consistently associated obesity and reoperation with this complication, while other risk factors such as use of 1 or both IMAs, duration and complexity of operation, and the presence of diabetes have been reported inconsistently. Most studies examining deep sternal wound infection have been single-center, retrospective reviews, and variation in wound surveillance techniques and the definition of deep sternal wound infection limit comparisons.
Obesity is a strong correlate of mediastinitis after CABG (59). In 1 report of 6,459 patients undergoing CABG at a single institution, Milano et al (60) found obesity to be the strongest independent predictor of mediastinitis (OR 1.3). In a prospective multi-institutional study, the Parisian Mediastinitis Study Group also found obesity to carry the greatest association with the development of postoperative mediastinitis (OR 2.44) (61). The mechanism by which obesity leads to this complication is poorly understood but is likely multifactorial. Perioperative antibiotics may be poorly distributed in adipose tissue, skin folds present a special challenge in maintaining sterility, and large regions of adipose tissue serve as an ideal substrate for bacteria and represent a clinical challenge for diagnosis when early infection occurs.
Another patient characteristic that has been associated with postoperative mediastinitis is the presence of diabetes (60,62), especially in patients requiring insulin (59). In addition to the microvascular changes seen in diabetic patients, elevated blood glucose levels may impair wound healing. The use of a strict protocol aimed at maintaining blood glucose levels 
200 mg/dL by the continuous, intravenous infusion of insulin has been shown to significantly reduce the incidence of deep sternal wound infection in diabetic patients (63,64).
Prior cardiac surgery is another factor associated with the development of mediastinitis (60,61,65). Reoperation requires additional dissection, longer perfusion times, more bleeding, and a higher likelihood of needing transfusion, variables that have all been linked to this complication.
Operator-dependent variables may also contribute to the development of deep sternal wound infection. These include the use of 1 or more IMAs for bypass conduits and excessive use of electrocautery for hemostasis (60,66). No studies have found the use of a single IMA to be predictive of mediastinitis. Two reports identified the use of both IMAs to be an independent predictor (61,62), while several others have shown no correlation with the development of mediastinitis (57,60). Because the use of both IMAs may predispose to devascularization of the sternum, it seems likely that this technique promotes infection, especially when combined with other risk factors such as diabetes and/or obesity.
In summary, deep sternal wound infection after CABG is an expensive and potentially lethal complication that appears to have a multifactorial etiology. Strategies to reduce the incidence of this complication include meticulous aseptic technique, keeping perfusion times to a minimum, avoidance of unnecessary electrocautery, appropriate use of perioperative antibiotics, and strict control of blood glucose levels during and after operation. Each of these is discussed in greater depth in Section IV, A4.
5. Morbidity associated with CABG: renal dysfunction
The first major multicenter study of renal dysfunction after CABG surgery has recently been published (67). This study of 2,222 patients who underwent myocardial revascularization with CPB defined postoperative renal dysfunction (PRD) as a postoperative serum creatinine level of 
2.0 mg/dL or an increase in the serum creatinine level of 0.7 mg/dL from preoperative to maximum postoperative values. PRD occurred in 171 (7.7%) of the patients studied; 30 of these (18%, or 1.4% of all study patients) required dialysis. The mortality rates were 0.9% among patients who did not develop PRD, 19% in patients with PRD who did not require dialysis, and 63% among those who required dialysis.
Several preoperative risk factors for PRD were identified, including advanced age, a history of moderate to severe CHF, prior CABG, type 1 diabetes mellitus, and preexisting renal disease (preoperative creatinine levels between 1.4 and 2.0 mg/dL). The risk of PRD in patients <70 years of age nearly tripled with 1 preoperative risk factor and increased further with 2 risk factors. A detailed analysis of the impact of these preoperative risk factors for PRD for 3 age groups is presented in Table 3. These findings allow identification of high-risk patients for PRD and a general estimation of the risk for PRD for an individual patient. The reported risk for patients with moderate renal dysfunction is consistent with previous reports from smaller, single-center studies (68–70).
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1.6 mg/dL in the 6 months before surgery and who did not require preoperative dialysis (74). The mean age of the patients was 71 years, and nearly 80% were males. The hospital mortality was 19%, and 26% of surviving patients required chronic dialysis. Among 19 patients with a creatinine level 2.6 mg/dL, 42% of survivors required chronic hemodialysis, whereas none of the surviving patients with a creatinine level 2.6 mg/dL required chronic dialysis. This study suggests that patients >70 years old with a creatinine level 2.6 mg/dL are at extreme risk for dialysis dependency after CABG, and alternative options for coronary management should be strongly considered. The importance of perioperative renal function is emphasized by a recent report that correlated acute renal failure sufficient to require dialysis and operative mortality after cardiac surgery (75). The 42,773 patients who underwent CABG or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality. This degree of acute renal failure occurred in 460 (1.1%) patients. Overall, operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. Acute renal failure requiring dialysis was independently associated with early mortality after cardiac surgery, even after adjustment for comorbidity and postoperative complications.
B. Posthospital outcomes. The extensive application of CABG has been a consequence of its effectiveness in the relief of angina and prolongation of survival in certain subsets. The 1991 Guidelines provided data that allow a general understanding of expectation after CABG (1). In a heterogeneous group of patients, survival at 5 years was 92% and at 10 years was 81%. Freedom from angina was 83% at 5 years and 63% at 10 years. The previous guidelines provided equations for predicting patient-specific outcomes, including freedom from unfavorable events, in a comparison of coronary bypass surgery versus medical treatment. These detailed predictive instruments remain appropriate for use and are not presented here. While a discussion of the comparative benefits of CABG versus medical therapy appears in Section III, C, a brief description of the factors that influence the long-term results of the operation is appropriate here.
The predictors of long-term survival after CABG have been analyzed in a number of studies. In an analysis of 23,960 patients from 1977 to 1994 from Emory University, advanced age, EF, presence of diabetes, number of diseased vessels, and sex were significant multivariate predictors of survival, while angina class, hypertension, history of MI, renal dysfunction, and CHF were other important factors identified by univariate analysis (Table 4) (76). Other studies have identified predictors for the recurrence of angina and for postoperative MI (Table 5). Importantly, untoward events after coronary bypass tend to increase in frequency between 5 and 10 years after the operation, apparently coincident with the gradual occlusion of vein grafts. Approximately 50% of vein grafts are closed by 10 years after operation.
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C. Comparison of medical therapies versus surgical revascularization. Since the 1991 Guidelines, relatively little clinical trial information comparing medical with surgical treatment of CAD has been published. However, longer follow-up of patients enrolled in the earlier, major randomized trials has solidified the appropriate indications for surgical treatment.
The traditional stratification of patients has been based on the extent of CAD (ie, number of vessels with anatomically significant disease and whether or not the major epicardial obstruction is proximal) in association with the extent of LV dysfunction (determined by a simple measure of global LVEF). The major end point of the studies has been survival. The major randomized trials enrolled patients between 1972 and 1984, at which time the predominant medical therapy was the use of ß-blockers and nitrates.
There are several important limitations of the randomized trials in view of current practice (Table 6). In the ensuing years, calcium channel blockers have been added, particularly for symptomatic patients. The use of aspirin has become more widespread in all patients with CAD. The role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and other lipid-lowering agents has now been recognized as important in reducing recurrent ischemic events. It is hoped that these agents will be used equally in patients treated with medications alone and in patients after CABG surgery, whose revascularization therapy is complemented by appropriate medical treatment to reduce ischemic complications. The contribution of recent advances in surgical revascularization techniques cannot be fully assessed. The potential value of arterial conduits for revascularization, particularly the IMA, cannot be evaluated from these early randomized studies, yet their use is now routine in CABG surgery. There are also no prospective, randomized studies comparing the more recent off-bypass or minimally invasive surgical approaches to medical therapy. Finally, the randomized trials oversimplify the designation of 1-, 2-, and 3-vessel disease. Several reports show that prognosis is also critically related to the location of lesions within vessels, not simply the number of vessels involved (9,18).
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2. Location and severity of stenoses
a. Left main disease
The benefit of surgery over medical treatment for patients with significant left main stenosis is little argued. All of the trials define significant left main stenosis as being >50% as judged by contrast angiography. The median survival for surgically treated patients is 13.3 years versus 6.6 years in medically treated patients (95,96).
Left main equivalent disease, defined as severe (70%) proximal LAD and proximal left circumflex disease, appears to behave similarly to true left main disease. Median survival for surgical patients is 13.1 years versus 6.2 years for medically assigned patients (95). However, there are few randomized or randomizable patients with this anatomy. By 15 years, there is less survival benefit for patients assigned to surgery. It is estimated that if all medical patients survived 15 years, 65% would eventually have surgery (88). At 15 years, cumulative survival in the CASS registry for patients with left main equivalent disease was 44% for surgical patients and 31% for the medical group (95,97,98).
b. Three-vessel disease
Significant CAD is defined variably in the major studies. CASS originally reported results with significant stenosis defined as 70%. The Veterans Administration and European studies used 50% as the cutoff for significant stenosis, and when the studies were combined for the meta-analysis (88), the 50% criterion defined significant disease for all vessels.
The outcome of patients with 3-vessel CAD assigned to surgical or medical treatment is similar at the 10-year follow-up to that reported earlier in randomized trials. The more severe the symptoms, the more proximal the LAD CAD, and the worse the LV function, the greater is the benefit from surgery (84,88,99–103). In patients with 3-vessel disease, the relative risk reduction for surgery at 5 years is 42% and at 10 years is 24%, with an increase in survival of 5.7 months at 10-year follow-up (88).
c. Proximal LAD disease
Proximal LAD CAD (>50% stenosis) is an important contributor to outcome. In patients with proximal LAD disease, the relative risk reduction of CABG at 5 years is 42% and at 10 years, 22%. In LAD disease without proximal involvement, the relative risk reduction at 5 years is 34% and at 10 years, 10%. In the presence of depressed LV function, the absolute benefit of surgery is greater because of the risk of this population (84,104).
d. LV function
LV systolic function remains an important predictor of which patients are likely to benefit from surgery (100–102,105). In patients with a normal EF, surgical revascularization provides little survival benefit. In patients with mild to moderately depressed function, the poorer the LV function, the greater is the potential benefit of surgery (100–102,106,107). The relative benefit is similar, but there is greater absolute benefit because of the high-risk profile of these patients. It is important to note that the randomized trials did not include patients with an LVEF <0.35. Thus, many of the patients operated on today were not well represented in the randomized trials.
A major growth in our understanding of the potential reversibility of chronic systolic dysfunction among patients with CAD has occurred in the past few years. Systolic dysfunction that is a result of chronic hypoperfusion ("hibernating") and not a result of infarction can now be identified noninvasively by positron emission tomographic scanning, radioisotope imaging, or dobutamine echocardiography. Patients with large areas of myocardial viability may benefit from revascularization. Small, observational studies of patients with hibernating myocardium who are undergoing coronary revascularization have shown functional and perhaps survival benefit, especially when LV function is particularly poor. This is discussed further in Section V, I.
There are few data regarding optimal choices for women. The higher early surgical mortality needs to be weighed against the lessons derived from the predominantly male subjects (108), and this as well as other subsets will be discussed in Section V.
e. Symptoms/quality of life
More attention has been paid recently to improvement in symptoms and quality of life measurements. The findings from randomized trials for these outcomes parallel those of the survival data. Apart from its effect on survival, CABG is potentially indicated for 2 symptom-based indications: to alleviate symptoms of angina pectoris over and above medical therapy and to reduce the incidence of nonfatal outcomes such as MI, CHF, and hospitalization. CABG is considered to improve or to relieve angina pectoris in a much broader group of patients than the subgroups in which it has been found to improve survival. Registry studies have suggested a favorable impact on late MI among highest-risk subsets, such as patients with 3-vessel disease and severe angina pectoris. However, in the pooled data from the randomized trials (88), no overall beneficial impact of CABG on subsequent MI could be demonstrated. This likely reflects an early increase in MI perioperatively in patients undergoing CABG surgery balanced by fewer MIs in the long term.
At 5 years, patients treated surgically used less antianginal medicines, with 63% of patients completely symptom-free compared with 38% of medically assigned patients (99). At 10 years, however, these differences were no longer significant. Patients treated surgically and medically used similar amounts of long-acting nitrates and ß-blockers, with 47% of surgical patients asymptomatic compared with 42% of medical patients. Recreational status, employment, frequency of CHF, use of other medicines, and hospitalization frequency were also similar between the groups (109–116).
At 10 years, the frequency of angina and other quality-of-life measurements were similar between surgically and medically treated groups. Those who have multivessel disease and who receive complete revascularization are less symptomatic, and symptom benefit is most apparent in patients with severe angina and LV dysfunction (EF <0.35) (109,111–117). Perhaps because of the symptomatic relief associated with surgical revascularization, the "crossover" from medical treatment to surgery may be of greater significance in improving quality of life. Medically assigned patients who had persistent angina despite medical therapy were able to undergo surgical revascularization and thus obtain relief of symptoms.
f. Loss of benefit of surgery
The meta-analysis based on individual patient data from all of the available randomized trials indicates a gradually increasing reduction in mortality over the first 5 to 7 years when coronary surgery is compared with medical therapy. After this period, at about the 10- to 12-year follow-up, there is a tendency of the survival curves to converge. This decreased long-term benefit has been shown in the individual studies as well and is likely due to a combination of factors. First, it is inevitable in studies with long-term follow-up that survival curves of various treatment groups will eventually merge. This result has to do with the reduced life expectancy of patients with coronary disease, regardless of treatment.
Second, there is an increased event rate in late follow-up of surgically assigned patients because of the progression of native and graft disease, with a disproportionate increase in late surgical mortality. Finally, crossover to surgery of medically assigned patients is important. Thus, high-risk, medically assigned patients may gain the "benefit" of surgery even when assigned to medical therapy. The crossover rate at 10 years is between 37% and 50%, and this may contribute to the better survival and improved quality of life in such "medically assigned" patients.
g. Summary
CABG improves long-term survival in a broad spectrum of patients at moderate to high risk with medical therapy. Although a relative risk reduction of 40% can be expected overall in comparison with medical therapy, absolute benefits are proportional to the expected risk with medical therapy. As such, absolute benefit is greatest among those at highest risk with medical therapy (5-year mortality >20%). Clinical and angiographic markers of risk, including severity of CAD, LV dysfunction, and myocardial ischemia, can identify patients in various risk strata.
D. Comparison with percutaneous techniques. Although PTCA was initially used only for the treatment of single-vessel CAD, advances in technique, equipment, and experience have resulted in its expanded use for patients with multivessel disease. In general, PTCA is less invasive and requires a shorter hospitalization and recovery time than does bypass surgery. However, the disadvantages of PTCA as initial therapy for coronary disease include restenosis of treated lesions and, compared with CABG, a lesser ability to revascularize all lesions in patients with multivessel disease. Recent clinical trials comparing PTCA and CABG have further defined the relative advantages and disadvantages of these treatments.
1. Overview of randomized trials
Nine randomized, clinical trials comparing PTCA and CABG have been published (Table 10). Before discussing the results of these trials, it is important to consider what we can expect to learn from them. A comparative trial must be large enough to have sufficient statistical power to detect a difference in survival, the usual primary end point. If no difference is observed between CABG and PTCA, it can be concluded that the treatments are equivalent only if trials are large enough to reliably detect or exclude relative differences in mortality of 20% and include a large number of patients in whom CABG has been shown to improve prognosis. Because 600 deaths would be needed in the "control" group to exclude a relative risk difference of 20% with 90% power, trials with 4,000 moderate- to high-risk patients per treatment arm would be needed. However, if a 30% risk difference is considered the smallest clinically important difference, trials of 2,000 patients in each group are required. Unfortunately, all of these trials excluded patients in whom survival had already been shown to be better with CABG when compared with medical therapy. Second, follow-up must be long enough (generally 4 to 5 years) to detect a survival advantage with either approach. Third, to reliably compare the 2 treatments, there must be a high rate of compliance with the original treatment allocation; if a substantial proportion of patients "cross over" (30% to 40% by 5 years), the ability to detect differences in survival decreases markedly. Finally, the patients enrolled in the trial must be similar to those not enrolled to allow generalization of the findings. All of the randomized trials fall short of 1 or more of these criteria. However, the largest of the 9 randomized trials, the Bypass Angioplasty Revascularization Investigation (BARI), comes closest to fulfilling these criteria and will be discussed in detail (118).
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The most important limitation of all of the randomized trials relates to the generalizability of the conclusions. The findings are not applicable to all patients with multivessel coronary disease for 2 reasons. First, only 5% of screened patients with multivessel disease were enrolled in the trials (119,120). In the BARI trial, >25,000 patients with multivessel coronary disease by diagnostic angiography were screened for eligibility. About 50% of these patients were ineligible because of left main disease, insufficient symptoms, or other reasons. One third of the remaining 4110 patients had multivessel disease suitable for both PTCA and CABG, and only half of these (7% of those screened) were enrolled in the randomized trial (121). Second, examination of the Emory Angioplasty versus Surgery Trial (EAST) registry suggests that physician judgment may be an important determinant of outcome that is eliminated by a randomized design. In this registry of 450 eligible patients who refused randomization, survival was slightly better than in the 392 randomized patients despite similar baseline features (122). This may reflect physician judgment, as CABG was utilized more often in patients with 3-vessel disease and PTCA more often in patients with 2-vessel disease (122).
The age range (mean age varied from 56 to 61 years) and sex distribution (20% female) were similar in most trials, although the Medicine, Angioplasty, or Surgery Study (MASS) trial had 42% women (123). All of the randomized trials excluded patients with low EFs and those for whom CABG was known to provide a survival advantage. Six trials included only patients with multivessel disease and 2, only single-vessel disease (MASS, Lausanne); the Randomized Intervention Treatment of Angina (RITA) trial included both (Table 10). Several trials were conducted in single centers, whereas RITA, the German Angioplasty Bypass-surgery Investigation (GABI), the Coronary Angioplasty versus Bypass Vascularization Investigation (CABRI), and BARI were multicenter. The CABRI and EAST trials permitted incomplete revascularization, whereas the others had a goal of complete revascularization. CABRI and RITA included vessels with total occlusion, accounting for the lower success rate of PTCA; the success rate for these vessels in RITA was only 48%. Asymptomatic patients were excluded from GABI, and the extent of coronary disease also varied widely. Three-vessel disease was present in only 12% and 18% of RITA and GABI subjects, respectively, and present in >40% of BARI and Estudio Randomizado Argentino de Angioplastia vs Cirugia (ERACI) patients. The incidence of diabetes mellitus varied from 10% to 12% (Toulouse, Goy, ERACI, GABI, and CABRI) to >20% (EAST and BARI). <
