Methods of Coronary Revascularization — Things May Not Be as They Seem
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《新英格兰医药杂志》
During the past three decades, randomized trials and registries have provided extensive evidence regarding the indications for and preferred method of coronary revascularization.1 The initial trials focused on indications for coronary-artery bypass grafting (CABG) versus medical therapy. Subsequent trials compared percutaneous transluminal coronary angioplasty (PTCA) with medical therapy, and CABG with PTCA. These were followed by comparisons of PTCA with devices and stents; one trial compared coronary revascularization with medical therapy in elderly patients.2
The New York registries of CABG and percutaneous coronary intervention (PCI), which were used in the study reported by Hannan et al. in this issue of the Journal,3 have been invaluable in determining outcomes and providing quality-assurance data because of the large numbers of patients entered, the comprehensive database of coexisting conditions, and the inclusion of all procedures performed in the state.3 In contrast to national data, a higher proportion of patients underwent CABG than PCI with stent implantation, although the number of patients treated with PTCA alone, who presumably were excluded, is unknown. The current analysis of almost 60,000 patients undergoing revascularization between January 1997 and December 2000, excluding those in whom revascularization was performed within 24 hours after myocardial infarction, underscores the previously well-documented higher rate of repeated revascularization after PCI than after CABG, but more important, demonstrates an advantage of CABG with respect to long-term survival. Because of major differences in baseline variables between the two groups (the surgical group included a "sicker" subgroup), survival curves were adjusted for baseline risk. These curves demonstrated a survival benefit for surgery in all subgroups with three-vessel disease, in patients with two-vessel disease and proximal left anterior descending coronary-artery involvement, and in some patients with two-vessel disease but without proximal left anterior descending coronary-artery involvement. Of particular interest and perhaps surprising is the finding that there were differences in survival after only three years.
Multiple trials of coronary revascularization in multivessel disease have suggested that survival is not compromised by an initial strategy of PCI, except in patients with diabetes. Therefore, the implications of this study are profound and suggest that things are not as clear-cut as originally thought. Reflecting on the findings of this study, we are reminded of the limitations of underpowered trials, particularly in lower-risk patients. All trials introduced a selection bias in that patients had to be eligible for both procedures, and most who were clinically eligible were excluded on angiographic grounds. Although this may change with technological advances in stents, two trials have demonstrated that patients enrolled represent only 5 to 12 percent of all patients undergoing revascularization at participating centers.4,5
Are these data consistent with the results of prior studies? What is new is the impressive advantage of surgery in the overall cohort and most subgroups. Most studies of coronary revascularization have emphasized a "gradient of risk": higher-risk subgroups, particularly patients with three-vessel disease, those with diffuse disease, those with left ventricular dysfunction, and perhaps those with diabetes, benefit more from CABG than do lower-risk subgroups in studies comparing CABG with medical therapy or PCI.6 This is readily explicable, since PCI is directed against a target "culprit" lesion as opposed to CABG, in which most of the epicardial vessel is bypassed, including the "future" culprits, which are responsible for most of the events once the rate of restenosis declines (Figure 1).7 The New York registry study, however, suggests that surgery may be superior in a larger group of patients than initially considered and underscores that trials of CABG versus PCI have been underpowered to detect small but significant differences in mortality. Indeed the original Bypass Angioplasty Revascularization (BARI) trial reported a statistically significant advantage of CABG over PTCA, but this was driven primarily by outcomes in patients with diabetes.8
Figure 1. Difference in the Approach to the Lesion with Percutaneous Coronary Intervention (PCI) and Coronary-Artery Bypass Grafting (CABG).
PCI is targeted at the "culprit" lesion or lesions, whereas CABG is directed at the epicardial vessel, including the "culprit" lesion or lesions and future culprits, a difference that may account for the superiority of CABG, at least in the intermediate term, in patients with multivessel disease.
Randomized trials and risk-adjusted analyses are potent methods of demonstrating the biostatistical superiority of one procedure over another. Nonetheless, much can be learned from raw data or unadjusted survival curves, which tell us about outcomes from the perspective of the patient. Data from the New York registry do not demonstrate substantial survival differences for the two-vessel–disease group overall, which is reassuring since most patients with two-vessel disease are treated with PCI. CABG is, however, the most widely and appropriately used treatment for three-vessel disease, particularly in association with left ventricular dysfunction. In this respect, an important lesson was learned from the BARI Registry of patients who were eligible for randomization but who were treated according to the preference of the patient and physician.9 Among patients with diabetes in the registry, outcomes were similar with PTCA and CABG, in contrast to large differences noted in favor of CABG in the trial. In the registry, therapy was based on clinical and angiographic findings, which led to PTCA being used in lower-risk patients and CABG in those at higher risk; that is, randomization highlighted the superiority of one procedure over another, but clinical judgment took this into account in selecting the optimal therapy for the individual patient. The magnitude of the difference in the trial was enhanced by the process of randomization in which many patients randomly assigned to PCI would have been steered toward CABG in a clinical practice environment.
Perhaps a similar situation occurs in the adjusted versus unadjusted analyses in the New York registry study by Hannan et al. PCI was used in 61 percent of patients with double-vessel disease, but it was used in only 42 percent with proximal left anterior descending coronary-artery disease and in only 14 percent with triple-vessel disease. If clinical judgment translates into a decision to use PCI in lower-risk patients with suitable coronary anatomy, preserved left ventricular function, and fewer coexisting conditions, this could be appropriate, given the similar, unadjusted outcomes in some subgroups. Should surgery be recommended for all patients with the same characteristics as the cohorts shown to have a better survival with CABG in this registry study? The question is appropriate, but as stated by the authors, many other considerations need to be weighed, including the patient's and physician's appreciation of periprocedural morbidity and mortality, a realistic perception of the effect of procedural outcomes on the quality of life, the effect of coexisting conditions, and the magnitude of the benefit of one procedure over another.
The developments in coronary revascularization devices and techniques during the past decade, including drug-eluting stents and off-pump coronary bypass, are a testimony to the constancy of change. To what extent will these developments alter the conclusions of prior trials and registry studies? Perhaps the impact of the "quiet revolution" characterized by the role of secondary prevention is yet to be realized. As the specter of restenosis recedes with the use of drug-eluting stents, prevention of disease progression in native vessels assumes increasing prominence, and future trials must focus on aggressive risk-factor reduction, and in patients with diabetes, glycemic control.7
Approximately 30 years after the first trials of coronary revascularization, new trials are asking the same questions but of different patients and in a changed therapeutic milieu. The realization that evidence-based medicine must take its place alongside clinical judgment is refreshing. Although the real world has many competitive pressures, our decisions regarding indications for revascularization and the preferred method should be made in the interest of the patient and in an atmosphere of collegiality. Such a goal would be enhanced by widespread participation of physicians in the decision-making process, including both interventional and noninterventional cardiologists and cardiac surgeons.
Source Information
From the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn.
References
Rihal CS, Raco DL, Gersh BJ, Yusuf S. Indications for coronary artery bypass surgery and percutaneous coronary intervention in chronic stable angina: review of the evidence and methodological considerations. Circulation 2003;108:2439-2445.
TIME Investigators. Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial. Lancet 2001;358:951-957.
Hannan EL, Racz MJ, Wallford G, et al. Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005;352:2174-2183.
The SoS Investigators. Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery Trial): a randomised controlled trial. Lancet 2002;360:965-970.
Detre KM, Rosen AD, Bost JE, et al. Contemporary practice of coronary revascularization in U.S. hospitals and hospitals participating in the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 1996;28:609-615.
Jones RH, Kesler K, Phillips HR III, et al. Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease. J Thorac Cardiovasc Surg 1996;111:1013-1025.
Cutlip DE, Chhabra AG, Baim DS, et al. Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials. Circulation 2004;110:1226-1230.
BARI Trial Investigators. Seven-year outcome in the Bypass Angioplasty Revascularization Investigation (BARI) by treatment and diabetic status. J Am Coll Cardiol 2000;35:1122-1129.
Detre KM, Guo P, Holubkov R, et al. Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Bypass Angioplasty Revascularization Investigation (BARI). Circulation 1999;99:633-640.(Bernard J. Gersh, M.B., C)
The New York registries of CABG and percutaneous coronary intervention (PCI), which were used in the study reported by Hannan et al. in this issue of the Journal,3 have been invaluable in determining outcomes and providing quality-assurance data because of the large numbers of patients entered, the comprehensive database of coexisting conditions, and the inclusion of all procedures performed in the state.3 In contrast to national data, a higher proportion of patients underwent CABG than PCI with stent implantation, although the number of patients treated with PTCA alone, who presumably were excluded, is unknown. The current analysis of almost 60,000 patients undergoing revascularization between January 1997 and December 2000, excluding those in whom revascularization was performed within 24 hours after myocardial infarction, underscores the previously well-documented higher rate of repeated revascularization after PCI than after CABG, but more important, demonstrates an advantage of CABG with respect to long-term survival. Because of major differences in baseline variables between the two groups (the surgical group included a "sicker" subgroup), survival curves were adjusted for baseline risk. These curves demonstrated a survival benefit for surgery in all subgroups with three-vessel disease, in patients with two-vessel disease and proximal left anterior descending coronary-artery involvement, and in some patients with two-vessel disease but without proximal left anterior descending coronary-artery involvement. Of particular interest and perhaps surprising is the finding that there were differences in survival after only three years.
Multiple trials of coronary revascularization in multivessel disease have suggested that survival is not compromised by an initial strategy of PCI, except in patients with diabetes. Therefore, the implications of this study are profound and suggest that things are not as clear-cut as originally thought. Reflecting on the findings of this study, we are reminded of the limitations of underpowered trials, particularly in lower-risk patients. All trials introduced a selection bias in that patients had to be eligible for both procedures, and most who were clinically eligible were excluded on angiographic grounds. Although this may change with technological advances in stents, two trials have demonstrated that patients enrolled represent only 5 to 12 percent of all patients undergoing revascularization at participating centers.4,5
Are these data consistent with the results of prior studies? What is new is the impressive advantage of surgery in the overall cohort and most subgroups. Most studies of coronary revascularization have emphasized a "gradient of risk": higher-risk subgroups, particularly patients with three-vessel disease, those with diffuse disease, those with left ventricular dysfunction, and perhaps those with diabetes, benefit more from CABG than do lower-risk subgroups in studies comparing CABG with medical therapy or PCI.6 This is readily explicable, since PCI is directed against a target "culprit" lesion as opposed to CABG, in which most of the epicardial vessel is bypassed, including the "future" culprits, which are responsible for most of the events once the rate of restenosis declines (Figure 1).7 The New York registry study, however, suggests that surgery may be superior in a larger group of patients than initially considered and underscores that trials of CABG versus PCI have been underpowered to detect small but significant differences in mortality. Indeed the original Bypass Angioplasty Revascularization (BARI) trial reported a statistically significant advantage of CABG over PTCA, but this was driven primarily by outcomes in patients with diabetes.8
Figure 1. Difference in the Approach to the Lesion with Percutaneous Coronary Intervention (PCI) and Coronary-Artery Bypass Grafting (CABG).
PCI is targeted at the "culprit" lesion or lesions, whereas CABG is directed at the epicardial vessel, including the "culprit" lesion or lesions and future culprits, a difference that may account for the superiority of CABG, at least in the intermediate term, in patients with multivessel disease.
Randomized trials and risk-adjusted analyses are potent methods of demonstrating the biostatistical superiority of one procedure over another. Nonetheless, much can be learned from raw data or unadjusted survival curves, which tell us about outcomes from the perspective of the patient. Data from the New York registry do not demonstrate substantial survival differences for the two-vessel–disease group overall, which is reassuring since most patients with two-vessel disease are treated with PCI. CABG is, however, the most widely and appropriately used treatment for three-vessel disease, particularly in association with left ventricular dysfunction. In this respect, an important lesson was learned from the BARI Registry of patients who were eligible for randomization but who were treated according to the preference of the patient and physician.9 Among patients with diabetes in the registry, outcomes were similar with PTCA and CABG, in contrast to large differences noted in favor of CABG in the trial. In the registry, therapy was based on clinical and angiographic findings, which led to PTCA being used in lower-risk patients and CABG in those at higher risk; that is, randomization highlighted the superiority of one procedure over another, but clinical judgment took this into account in selecting the optimal therapy for the individual patient. The magnitude of the difference in the trial was enhanced by the process of randomization in which many patients randomly assigned to PCI would have been steered toward CABG in a clinical practice environment.
Perhaps a similar situation occurs in the adjusted versus unadjusted analyses in the New York registry study by Hannan et al. PCI was used in 61 percent of patients with double-vessel disease, but it was used in only 42 percent with proximal left anterior descending coronary-artery disease and in only 14 percent with triple-vessel disease. If clinical judgment translates into a decision to use PCI in lower-risk patients with suitable coronary anatomy, preserved left ventricular function, and fewer coexisting conditions, this could be appropriate, given the similar, unadjusted outcomes in some subgroups. Should surgery be recommended for all patients with the same characteristics as the cohorts shown to have a better survival with CABG in this registry study? The question is appropriate, but as stated by the authors, many other considerations need to be weighed, including the patient's and physician's appreciation of periprocedural morbidity and mortality, a realistic perception of the effect of procedural outcomes on the quality of life, the effect of coexisting conditions, and the magnitude of the benefit of one procedure over another.
The developments in coronary revascularization devices and techniques during the past decade, including drug-eluting stents and off-pump coronary bypass, are a testimony to the constancy of change. To what extent will these developments alter the conclusions of prior trials and registry studies? Perhaps the impact of the "quiet revolution" characterized by the role of secondary prevention is yet to be realized. As the specter of restenosis recedes with the use of drug-eluting stents, prevention of disease progression in native vessels assumes increasing prominence, and future trials must focus on aggressive risk-factor reduction, and in patients with diabetes, glycemic control.7
Approximately 30 years after the first trials of coronary revascularization, new trials are asking the same questions but of different patients and in a changed therapeutic milieu. The realization that evidence-based medicine must take its place alongside clinical judgment is refreshing. Although the real world has many competitive pressures, our decisions regarding indications for revascularization and the preferred method should be made in the interest of the patient and in an atmosphere of collegiality. Such a goal would be enhanced by widespread participation of physicians in the decision-making process, including both interventional and noninterventional cardiologists and cardiac surgeons.
Source Information
From the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn.
References
Rihal CS, Raco DL, Gersh BJ, Yusuf S. Indications for coronary artery bypass surgery and percutaneous coronary intervention in chronic stable angina: review of the evidence and methodological considerations. Circulation 2003;108:2439-2445.
TIME Investigators. Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial. Lancet 2001;358:951-957.
Hannan EL, Racz MJ, Wallford G, et al. Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005;352:2174-2183.
The SoS Investigators. Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery Trial): a randomised controlled trial. Lancet 2002;360:965-970.
Detre KM, Rosen AD, Bost JE, et al. Contemporary practice of coronary revascularization in U.S. hospitals and hospitals participating in the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 1996;28:609-615.
Jones RH, Kesler K, Phillips HR III, et al. Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease. J Thorac Cardiovasc Surg 1996;111:1013-1025.
Cutlip DE, Chhabra AG, Baim DS, et al. Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials. Circulation 2004;110:1226-1230.
BARI Trial Investigators. Seven-year outcome in the Bypass Angioplasty Revascularization Investigation (BARI) by treatment and diabetic status. J Am Coll Cardiol 2000;35:1122-1129.
Detre KM, Guo P, Holubkov R, et al. Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Bypass Angioplasty Revascularization Investigation (BARI). Circulation 1999;99:633-640.(Bernard J. Gersh, M.B., C)