- Email: [email protected]
Time for Coronary Artery Bypass Grafting to Make a Comeback?
NEWS AND VIEWS
Time for Coronary Artery Bypass Grafting to Make a Comeback? David Taggart During the last year, the 3-year outcome data from the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial in overall results, results for 3-vessel disease,1 and results for left main disease2 have provided important insights into contemporary results of coronary revascularization either by stenting or surgery. EXISTING EVIDENCE BEFORE SYNTAX The authors of 2 metaanalyses published in 2009 compared outcomes of coronary arterial bypass grafting (CABG) and percutaneous coronary intervention (PCI). Hlatky and colleagues3 published a collaborative analysis of individual patient data from 10 randomized trials involving 7812 patients with median follow-up of 6 years. The overall rate of mortality was lower for CABG than PCI but did not reach conventional statistical significance (hazard ratio [HR] 0.9; P ⫽ 0.12). However, mortality was significantly lower with the use of CABG than PCI in patients with diabetes (HR 0.7) and those older than 65 years of age (HR 0.82). The overall combined composite end point of death or repeat intervention was 10% for CABG and 25% for PCI (P ⬍ 0.0001). Jeremiah and colleagues4 studied the impact of revascularization on mortality in patients with nonacute coronary artery disease. They identified 28 studies between 1977 and 2007 involving more than 13,000 patients, of whom 6476 underwent revascularization and 6645 were treated with optimal medical therapy. At a median follow-up at 3 years, the overall HR for death with revascularization was 0.74, being far more favorable with CABG (HR 0.62) than with PCI (HR 0.82). However, as repeatedly emphasized,5,6 these randomized trials often involved very low-risk patients
Department of Cardiovascular Surgery, University of Oxford, Oxford, United Kingdom. Disclosure: Dr. Taggart reports receiving consulting fees from Medtronic, VGS, and AstroZeneca and lecture fees from Abbot Vascular. Address reprint requests to Lisa Jones, Department of Cardiovascular Surgery, University of Oxford, Oxford Heart Centre, 71 Plantation Road, Oxford OX2 6JE, United Kingdom. E-mail: [email protected]
1043-0679/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2011.04.004
who are atypical of those encountered in real clinical practice. As reported previously, these randomized trials only enrolled approximately 5% of the eligible population, most of whom had single- or doublevessel coronary disease and normal left ventricular function and therefore were unlikely to gain any prognostic benefit from CABG. Likewise, these trials largely excluded patients with 3-vessel and left main disease, the population traditionally that is considered to derive prognostic benefit from CABG. Further interpretation of any conclusions drawn from these trials is also undermined by short durations of follow-up and a large number of patient crossovers, both of which tend to minimize the real benefits of CABG over the longer term. By contrast, several propensity match registries,5 containing data on several thousands of patients consistently suggest a strong survival benefit of CABG of approximately 5% by 3-5 years accompanied by a 6-fold reduction in the need for repeat intervention in comparison with PCI. However, propensity-matched registries must also be interpreted cautiously because it is not possible to exclude all known or potentially unknown confounding factors. THE SYNTAX TRIAL In recognition of reduced target vessel revascularization with the use of drug-eluting stents compared with bare metal stents, the SYNTAX trial was deigned to compare CABG versus PCI by the use of drug-eluting stents.7 The SYNTAX trial was unique both because it was a relatively “all-comer” trial in comparison with the very highly selected patient populations in previous trials and also because it contained a nested parallel registry to examine outcomes in patients deemed ineligible for randomization. SYNTAX, therefore, had a randomized component with 1800 patients and a registry component with 1275 patients of whom 1077, ie, 84%, were CABG patients. In other words, approximately one-third of all potential patients had coronary artery disease of such severity that they were deemed ineligible for randomization and were referred for CABG. Of the 1800 randomized patients 1095 patients had 3-vessel coronary disease, of whom 546 underwent PCI and 549 CABG. Mortality at 3 years was 5
TIME FOR CABG TO MAKE A COMEBACK? 5.7% CABG and 9.5% for PCI, ie, almost a 4% difference, which was both clinically and statistically highly significant (P ⫽ 0.02).1 The incidence of cerebrovascular accident in patients with 3-vessel disease was similar at 3 years at 2.6% for PCI and 2.9% for CABG. CABG also, however, resulted in a marked reduction in the risk of myocardial infarction (3.3 vs 7.1%; P ⫽ 0.005) and for the need for repeat revascularization (19% vs 29%; P ⬍ 0.001). According to the severity of coronary artery disease divided by SYNTAX scores in to low (SYNTAX ⬍22) intermediate (SYNTAX 23-32), and high (SYNTAX ⬎32), the major benefits of CABG were seen in those in the intermediate- and higher-risk groups. Indeed, approximately 79% of all patients with 3-vessel disease had SYNTAX scores greater than 22, implying that in these patients there is a marked survival advantage with CABG. It is noteworthy that this conclusion is also entirely consistent with the findings from several propensity matched registries.5 For left main disease, there appeared a different picture to that for 3-vessel disease. In a previous review in the literature we had documented that up to 90% of left main lesions are distal bifurcation lesions that are very at very high risk of restenosis with PCI, whereas up to 90% of patients also have multivessel coronary disease, for whom CABG already offers a survival advantage independent of the left main.8 In SYNTAX there were 705 patients with left main disease randomized to either PCI (number ⫽ 357) or CABG (number ⫽ 348). Total mortality at 3 years was 8.4% for CABG and 7.3% for PCI (P ⫽ 0.64). In contrast to 3-vessel disease, the incidence of stroke was 4% for CABG and 1.2% for PCI (P ⫽ 0.002), and the respective incidence of myocardial infarction 4.1% for CABG and 6.9% for PCI (P ⫽ 0.14). Overall revascularization was slightly less frequent, with CABG at 22.3% vs 26.8% for PCI. However, when the patients were subdivided again according to SYNTAX scores of low, intermediate, and high risk, the low-risk (2.6% vs 6%) and intermediate-risk (4.9% vs 12.4%) patients had a lower risk of death with PCI than CABG. However, in the higherrisk group, the risk of death with PCI was 13.4% vs 7.6% for CABG and with an almost 3-fold increase in need for repeat revascularization with PCI (27.7% vs 9.2% P ⫽ 0.001). Therefore, a new trial, the EXCEL trial, which started enrolling patients in 2010, will randomize approximately 2600 patients with low or intermediate left main to PCI or CABG. What is vitally important in this trial is that patients with SYNTAX scores greater than 32, ie, almost two-thirds of 6
all left main patients, are excluded because of the findings in SYNTAX trial. IMPACT OF RECENT STUDIES ON THE NEW EUROPEAN SOCIETY OF CARDIOLOGY/EUROPEAN ASSOCIATION FOR CARDIOTHORACIC SURGERY GUIDELINES ON MYOCARDIAL REVASCULARIZATION This extensive document has recently been published as a joint effort between the European Society of Cardiology and the European Association for Cardiothoracic Surgery with 25 members from 13 countries and equally balanced between noninterventional and interventional cardiologists and cardiac surgeons.9 Table 9 of these guidelines compares the relative efficacy of PCI versus CABG in 8 anatomic patterns of coronary disease. Four categories address coronary disease not involving the left main (ie, subdivided into 1- or 2-vessel disease with or without proximal left anterior descending artery involvement, and 3-vessel disease according to SYNTAX scores greater or less than 22). An additional 4 categories address the left main, subdivided into ostial or mid-shaft lesions with or without 1-vessel coronary disease, and distal bifurcation lesions subdivided by SYNTAX scores greater than or less than 32. In 7 of the 8 categories, CABG is still classified as a-1A indication for revascularization, whereas most PCI classifications are 2 A or 2B. However, for patients with 3-vessel disease with SYNTAX scores greater than ⬎22 and for left main disease with SYNTAX scores greater than 32, these are still considered class III indications for PCI. Of crucial importance, the guidelines also address in detail the importance of patient information and consent, the need for multidisciplinary heart teams, and that “ad hoc” PCI should not be the default position for most patients because it undermines the principle of informed consent. Furthermore, local protocols determined by these guidelines means that treatment can be recommended in most patients without the need for systematic discussion by the Heart Team. CONCLUSIONS According to the findings of SYNTAX almost 80% of all patients with 3-vessel disease and two-thirds with left main stem stenosis have a marked survival advantage with CABG and a marked reduction in the need for repeat revascularization. There is no difference in the incidence of stroke at 3 years between PCI and CABG for patients with 3-vessel disease but a greater incidence of stroke with CABG in patients
Seminars in Thoracic and Cardiovascular Surgery ● Volume 23, Number 1
TIME FOR CABG TO MAKE A COMEBACK? with left main disease (4% vs 1%). The survival benefit and freedom from repeat intervention for CABG patients in the SYNTAX trial is entirely consistent
1. Mohr FW: SYNTAX 3VD: Three-year outcomes from a prospective randomized trial of paclitaxel-eluting stents compared to bypass graft surgery in patients with triple vessel coronary artery disease. Transcatheter Cardiovascular Therapeutics Symposium, Washington, 2010 2. Serruys PW: SYNTAX left main: Three-year outcomes from a prospective randomized trial of paclitaxel-eluting stents compared to bypass graft surgery in patients with left main coronary artery disease. Transcatheter Cardiovascular Therapeutics Symposium, Washington, 2010 3. Hlatky MA, Boothroyd DB, Bravata DM, et al: Coronary artery bypass surgery compared with percutaneous coronary interventions for multi-
4.
5.
6. 7.
with evidence from numerous propensity matched registries. It is time, therefore, for CABG to make a comeback.
vessel disease: A collaborative analysis of individual patient data from ten randomised trials. Lancet 373:1190-1197, 2009 Jeremias A, Kaul S, Rosengart TK, et al: The impact of revascularization on mortality in patients with nonacute coronary artery disease. Am J Med 122:152-161, 2009 Taggart DP, Thomas BF: Lecture. Coronary artery bypass grafting is still the best treatment for multivessel and left main disease, but patients need to know. Ann Thorac Surg 82:1966-1975, 2006 Taggart DP: PCI or CABG in coronary artery disease? Lancet 373:1150-1152, 2009 Serruys PW, Morice MC, Kappetein AP, et al; SYNTAX Investigators: Percutaneous coronary
Seminars in Thoracic and Cardiovascular Surgery ● Volume 23, Number 1
intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 360:961-972, 2009 8. Taggart DP, Kaul S, Boden WE, et al: Revascularization for unprotected left main stem coronary artery stenosis stenting or surgery. J Am Coll Cardiol 51:885-892, 2008 9. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for CardioThoracic Surgery (EACTS): European Association for Percutaneous Cardiovascular Interventions (EAPCI), Kolh P, Wijns W, Danchin N, et al: Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 38 Suppl:S1S52, 2010
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Time for Coronary Artery Bypass Grafting to Make a Comeback? David Taggart During the last year, the 3-year outcome data from the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial in overall results, results for 3-vessel disease,1 and results for left main disease2 have provided important insights into contemporary results of coronary revascularization either by stenting or surgery. EXISTING EVIDENCE BEFORE SYNTAX The authors of 2 metaanalyses published in 2009 compared outcomes of coronary arterial bypass grafting (CABG) and percutaneous coronary intervention (PCI). Hlatky and colleagues3 published a collaborative analysis of individual patient data from 10 randomized trials involving 7812 patients with median follow-up of 6 years. The overall rate of mortality was lower for CABG than PCI but did not reach conventional statistical significance (hazard ratio [HR] 0.9; P ⫽ 0.12). However, mortality was significantly lower with the use of CABG than PCI in patients with diabetes (HR 0.7) and those older than 65 years of age (HR 0.82). The overall combined composite end point of death or repeat intervention was 10% for CABG and 25% for PCI (P ⬍ 0.0001). Jeremiah and colleagues4 studied the impact of revascularization on mortality in patients with nonacute coronary artery disease. They identified 28 studies between 1977 and 2007 involving more than 13,000 patients, of whom 6476 underwent revascularization and 6645 were treated with optimal medical therapy. At a median follow-up at 3 years, the overall HR for death with revascularization was 0.74, being far more favorable with CABG (HR 0.62) than with PCI (HR 0.82). However, as repeatedly emphasized,5,6 these randomized trials often involved very low-risk patients
Department of Cardiovascular Surgery, University of Oxford, Oxford, United Kingdom. Disclosure: Dr. Taggart reports receiving consulting fees from Medtronic, VGS, and AstroZeneca and lecture fees from Abbot Vascular. Address reprint requests to Lisa Jones, Department of Cardiovascular Surgery, University of Oxford, Oxford Heart Centre, 71 Plantation Road, Oxford OX2 6JE, United Kingdom. E-mail: [email protected]
1043-0679/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2011.04.004
who are atypical of those encountered in real clinical practice. As reported previously, these randomized trials only enrolled approximately 5% of the eligible population, most of whom had single- or doublevessel coronary disease and normal left ventricular function and therefore were unlikely to gain any prognostic benefit from CABG. Likewise, these trials largely excluded patients with 3-vessel and left main disease, the population traditionally that is considered to derive prognostic benefit from CABG. Further interpretation of any conclusions drawn from these trials is also undermined by short durations of follow-up and a large number of patient crossovers, both of which tend to minimize the real benefits of CABG over the longer term. By contrast, several propensity match registries,5 containing data on several thousands of patients consistently suggest a strong survival benefit of CABG of approximately 5% by 3-5 years accompanied by a 6-fold reduction in the need for repeat intervention in comparison with PCI. However, propensity-matched registries must also be interpreted cautiously because it is not possible to exclude all known or potentially unknown confounding factors. THE SYNTAX TRIAL In recognition of reduced target vessel revascularization with the use of drug-eluting stents compared with bare metal stents, the SYNTAX trial was deigned to compare CABG versus PCI by the use of drug-eluting stents.7 The SYNTAX trial was unique both because it was a relatively “all-comer” trial in comparison with the very highly selected patient populations in previous trials and also because it contained a nested parallel registry to examine outcomes in patients deemed ineligible for randomization. SYNTAX, therefore, had a randomized component with 1800 patients and a registry component with 1275 patients of whom 1077, ie, 84%, were CABG patients. In other words, approximately one-third of all potential patients had coronary artery disease of such severity that they were deemed ineligible for randomization and were referred for CABG. Of the 1800 randomized patients 1095 patients had 3-vessel coronary disease, of whom 546 underwent PCI and 549 CABG. Mortality at 3 years was 5
TIME FOR CABG TO MAKE A COMEBACK? 5.7% CABG and 9.5% for PCI, ie, almost a 4% difference, which was both clinically and statistically highly significant (P ⫽ 0.02).1 The incidence of cerebrovascular accident in patients with 3-vessel disease was similar at 3 years at 2.6% for PCI and 2.9% for CABG. CABG also, however, resulted in a marked reduction in the risk of myocardial infarction (3.3 vs 7.1%; P ⫽ 0.005) and for the need for repeat revascularization (19% vs 29%; P ⬍ 0.001). According to the severity of coronary artery disease divided by SYNTAX scores in to low (SYNTAX ⬍22) intermediate (SYNTAX 23-32), and high (SYNTAX ⬎32), the major benefits of CABG were seen in those in the intermediate- and higher-risk groups. Indeed, approximately 79% of all patients with 3-vessel disease had SYNTAX scores greater than 22, implying that in these patients there is a marked survival advantage with CABG. It is noteworthy that this conclusion is also entirely consistent with the findings from several propensity matched registries.5 For left main disease, there appeared a different picture to that for 3-vessel disease. In a previous review in the literature we had documented that up to 90% of left main lesions are distal bifurcation lesions that are very at very high risk of restenosis with PCI, whereas up to 90% of patients also have multivessel coronary disease, for whom CABG already offers a survival advantage independent of the left main.8 In SYNTAX there were 705 patients with left main disease randomized to either PCI (number ⫽ 357) or CABG (number ⫽ 348). Total mortality at 3 years was 8.4% for CABG and 7.3% for PCI (P ⫽ 0.64). In contrast to 3-vessel disease, the incidence of stroke was 4% for CABG and 1.2% for PCI (P ⫽ 0.002), and the respective incidence of myocardial infarction 4.1% for CABG and 6.9% for PCI (P ⫽ 0.14). Overall revascularization was slightly less frequent, with CABG at 22.3% vs 26.8% for PCI. However, when the patients were subdivided again according to SYNTAX scores of low, intermediate, and high risk, the low-risk (2.6% vs 6%) and intermediate-risk (4.9% vs 12.4%) patients had a lower risk of death with PCI than CABG. However, in the higherrisk group, the risk of death with PCI was 13.4% vs 7.6% for CABG and with an almost 3-fold increase in need for repeat revascularization with PCI (27.7% vs 9.2% P ⫽ 0.001). Therefore, a new trial, the EXCEL trial, which started enrolling patients in 2010, will randomize approximately 2600 patients with low or intermediate left main to PCI or CABG. What is vitally important in this trial is that patients with SYNTAX scores greater than 32, ie, almost two-thirds of 6
all left main patients, are excluded because of the findings in SYNTAX trial. IMPACT OF RECENT STUDIES ON THE NEW EUROPEAN SOCIETY OF CARDIOLOGY/EUROPEAN ASSOCIATION FOR CARDIOTHORACIC SURGERY GUIDELINES ON MYOCARDIAL REVASCULARIZATION This extensive document has recently been published as a joint effort between the European Society of Cardiology and the European Association for Cardiothoracic Surgery with 25 members from 13 countries and equally balanced between noninterventional and interventional cardiologists and cardiac surgeons.9 Table 9 of these guidelines compares the relative efficacy of PCI versus CABG in 8 anatomic patterns of coronary disease. Four categories address coronary disease not involving the left main (ie, subdivided into 1- or 2-vessel disease with or without proximal left anterior descending artery involvement, and 3-vessel disease according to SYNTAX scores greater or less than 22). An additional 4 categories address the left main, subdivided into ostial or mid-shaft lesions with or without 1-vessel coronary disease, and distal bifurcation lesions subdivided by SYNTAX scores greater than or less than 32. In 7 of the 8 categories, CABG is still classified as a-1A indication for revascularization, whereas most PCI classifications are 2 A or 2B. However, for patients with 3-vessel disease with SYNTAX scores greater than ⬎22 and for left main disease with SYNTAX scores greater than 32, these are still considered class III indications for PCI. Of crucial importance, the guidelines also address in detail the importance of patient information and consent, the need for multidisciplinary heart teams, and that “ad hoc” PCI should not be the default position for most patients because it undermines the principle of informed consent. Furthermore, local protocols determined by these guidelines means that treatment can be recommended in most patients without the need for systematic discussion by the Heart Team. CONCLUSIONS According to the findings of SYNTAX almost 80% of all patients with 3-vessel disease and two-thirds with left main stem stenosis have a marked survival advantage with CABG and a marked reduction in the need for repeat revascularization. There is no difference in the incidence of stroke at 3 years between PCI and CABG for patients with 3-vessel disease but a greater incidence of stroke with CABG in patients
Seminars in Thoracic and Cardiovascular Surgery ● Volume 23, Number 1
TIME FOR CABG TO MAKE A COMEBACK? with left main disease (4% vs 1%). The survival benefit and freedom from repeat intervention for CABG patients in the SYNTAX trial is entirely consistent
1. Mohr FW: SYNTAX 3VD: Three-year outcomes from a prospective randomized trial of paclitaxel-eluting stents compared to bypass graft surgery in patients with triple vessel coronary artery disease. Transcatheter Cardiovascular Therapeutics Symposium, Washington, 2010 2. Serruys PW: SYNTAX left main: Three-year outcomes from a prospective randomized trial of paclitaxel-eluting stents compared to bypass graft surgery in patients with left main coronary artery disease. Transcatheter Cardiovascular Therapeutics Symposium, Washington, 2010 3. Hlatky MA, Boothroyd DB, Bravata DM, et al: Coronary artery bypass surgery compared with percutaneous coronary interventions for multi-
4.
5.
6. 7.
with evidence from numerous propensity matched registries. It is time, therefore, for CABG to make a comeback.
vessel disease: A collaborative analysis of individual patient data from ten randomised trials. Lancet 373:1190-1197, 2009 Jeremias A, Kaul S, Rosengart TK, et al: The impact of revascularization on mortality in patients with nonacute coronary artery disease. Am J Med 122:152-161, 2009 Taggart DP, Thomas BF: Lecture. Coronary artery bypass grafting is still the best treatment for multivessel and left main disease, but patients need to know. Ann Thorac Surg 82:1966-1975, 2006 Taggart DP: PCI or CABG in coronary artery disease? Lancet 373:1150-1152, 2009 Serruys PW, Morice MC, Kappetein AP, et al; SYNTAX Investigators: Percutaneous coronary
Seminars in Thoracic and Cardiovascular Surgery ● Volume 23, Number 1
intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 360:961-972, 2009 8. Taggart DP, Kaul S, Boden WE, et al: Revascularization for unprotected left main stem coronary artery stenosis stenting or surgery. J Am Coll Cardiol 51:885-892, 2008 9. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for CardioThoracic Surgery (EACTS): European Association for Percutaneous Cardiovascular Interventions (EAPCI), Kolh P, Wijns W, Danchin N, et al: Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 38 Suppl:S1S52, 2010
7