Iwould like to thank the Society of Thoracic Surgery

Transcription

1 THOMAS B. FERGUSON LECTURE Coronary Artery Bypass Grafting is Still the Best Treatment for Multivessel and Left Main Disease, But Patients Need to Know David P. Taggart, MD(Hons), PhD John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom Iwould like to thank the Society of Thoracic Surgery and, in particular, Dr Sydney Levitsky, the President, for the honor and privilege of presenting this Sixth Annual Thomas B. Ferguson Lecture. Dr Ferguson (Fig 1) is unquestionably one of the outstanding cardiothoracic surgeons of his generation. He is one of the few surgeons to have been both President of the AATS and STS, editor of Annals of Thoracic Surgery from 1984 to 2000, during which time he considerably raised both the academic and international profile of the journal, and is currently senior editor of CTS net. The Ferguson Lecture was established by the STS in 2000 to recognize and honor Dr Ferguson and the profound and far reaching influence of his contributions to the specialty of cardiothoracic surgery. Dr Ferguson is described by the STS as a consummate physician and friend to his patients, a widely recognized teacher to students and residents, a respected colleague to all cardiothoracic surgeons and a leader in developing the communication capabilities essential to continuing education. It is therefore a considerable honor and privilege to deliver this lecture. The STS stipulates that the subject matter of the lecture should address new and powerful external forces shaping the future of patient care. Consequently, previous lectures have dealt with issues such as public and health care policy, ethics, economics, and the development and dissemination of new technologies as powerful forces impacting on how cardiothoracic surgeons care for their patients. And it is the last issue the increasing distortion of an evidence-based surgical practice in favor of an unproven technology that I intend to address. I believe that the biggest threat today to patient care is the increasingly inappropriate (non-evidence-based) use of percutaneous coronary intervention (PCI) rather than coronary artery bypass grafting (CABG) in patients with multivessel and left main disease. Let me emphasize from the outset, however, that in some subsets of multivessel disease and left main stem stenosis, or in patients unfit for surgery, PCI can be a very Presented at the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30 Feb 1, Address correspondence to Dr Taggart, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; david. taggart@orh.nhs.uk. effective and worthwhile intervention. My criticisms, however, are aimed at the increasing, inappropriate, and non-evidence-based use of PCI as the default treatment in the wider population of patients with multivessel disease (and increasingly left main stem stenosis). I believe that such a position ignores consistently strong evidence from randomized trials and large real-world registries that CABG is a more effective treatment in terms of survival and freedom from recurrent angina and reintervention, and consequently, PCI denies patients the most effective treatment, and in particular, the prognostic benefit of surgery. The Inappropriate Use of PCI I would like to illustrate this point with two recent patient referrals that are representative of what increasingly occurs in clinical practice. The first was a 64-year-old patient with stable angina and severe three-vessel disease on angiography. This patient underwent repeated percutaneous intervention, receiving five stents (including two drug-eluting stents) over a 2-year period. CABG was not initially discussed as an option. The patient was never quite free from angina, and only a further recent deterioration finally prompted his referral for CABG. The second was a 66-year-old insulin-dependent diabetic patient with unstable angina. A cardiologic investigation demonstrated severe threevessel disease, including an occluded circumflex coronary artery. The patient received four drugeluting stents (three to the right coronary artery, one to the left anterior descending, and the circumflex was left occluded). The option of CABG was never discussed, and the interventional cardiologist who had discharged the patient back to the care of the noninterventional cardiologist was therefore unaware that the patient re-presented with unstable angina and required urgent CABG 6 months later. In both of these cases, I believe that failure to discuss CABG meant that not only were the patients denied the best treatment option but also the consents for PCI were obtained inappropriately as a consequence. In other 2006 by The Society of Thoracic Surgeons Ann Thorac Surg 2006;82: /06/$32.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg FERGUSON LECTURE TAGGART 2006;82: CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 1967 Fig 1. Dr Thomas B. Ferguson. words, without CABG having been discussed as an option, the patient had not, in effect, consented to PCI. PCI Versus CABG: History and Current Trends CABG was first performed in 1962 and has been used in multivessel and left main stem disease for almost 40 years (Table 1), and I will show that the evidence for its efficacy in this setting is strong. In contrast, PCI has been around for almost three decades (first used in 1977) and has been used in multivessel and left main disease for about 10 years. In contrast to CABG, I will demonstrate that the evidence for the efficacy of PCI in these situations is weak (or nonexistent). Both PCI and CABG have benefited from improved medical therapy, including aspirin, statins, and angiotensin-converting enzyme inhibitors, and both have witnessed technologic advances such as arterial grafts and off-pump surgery for CABG and drug-eluting stents for PCI. In the United Kingdom in 1998, equivalent numbers of PCI and CABG were each being performed in about 25,000 patients. The number of CABG procedures has plateaued, but the number of PCIs has increased exponentially, so that the current ratio in the United Kingdom is now approaching 3 patients undergoing PCI for every patient undergoing CABG [1]. This spectacular growth of PCI has caused panic in surgeons. Several articles have appeared in both the medical and lay press suggesting that it is time for heart surgeons to rethink their career. Indeed, in a relatively recent issue of the online journal CXVascular, the main headline stated Cardiac Surgeons Must Diversify or Perish [2]. With headlines like, this panic may be justified, but is there actual evidence of efficacy of PCI to make such headlines justifiable? PCI in Multivessel Disease: A Surgical Perspective There are two issues that are no longer debatable. The first is that patients want less invasive treatment, and that used appropriately, PCI can be a very effective treatment. But three important questions remain: 1. Is the current use of PCI in multivessel disease actually evidence based? 2. Are the limitations and risks of PCI explained to patients? It is stipulated by the General Medical Council in the United Kingdom that patients must be made aware of alternative and more effective treatments. Patients should be informed that angina relief and freedom from cardiac events, notably myocardial infarction and long-term survival, are significantly improved with CABG compared with PCI. If patients are not told this, then consent for PCI is obtained inappropriately. 3. Does it represent value for money? Do numerous/repeat PCI make economic or medical sense? So when a cardiologist states, patients want less invasive treatment, this is usually predicated on the assumption by the patient that both treatments are equally effective. In clinical practice, however, the patient is rarely informed that PCI is not as effective as CABG and impairs survival when compared with CABG. Current State of CABG Before CABG is confined to the history books, it is worth reemphasising that it is a very safe and effective procedure. The follow-up data on CABG extends beyond 40 years, and no other surgical intervention has been so regularly and rigorously scrutinized. In the United Kingdom, for the last few years, the hospital mortality for all primary CABG operations has remained at about 2%, and this is despite the fact that about one third of patients Table 1. Coronary Artery Bypass Grafting versus Percutaneous Coronary Intervention: History and Current Trends CABG PCI Initial use Use in MVD and LMD 35 years 10 years Evidence for efficacy in MVD and LMD Strong Weak Improved medical therapy Technical advances Aspirin, statins, ACEI Arterial grafts OPCABG Aspirin, statins, ACEI DES CABG coronary artery bypass grafting; PCI percutaneous coronary intervention; MVD multivessel disease; LMD left main disease; ACEI angiotensin-converting enzyme inhibitor; DES drug-eluting stents; OPCABG off-pump coronary artery bypass grafting.

3 1968 FERGUSON LECTURE TAGGART Ann Thorac Surg CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 2006;82: would be considered high risk because of factors such as urgency of operation, advanced age, impaired ventricular function, and coexistent morbidity [3]. In lower-risk patients, the mortality and major morbidity risk is even less. A recent meta-analysis of 37 randomized trials comparing on-pump and off-pump CABG and involving almost 3400 patients found the 30-day mortality was 1% [4]. In the Arterial Revascularization Trial (ART), a current randomized trial of single versus bilateral internal mammary artery [5] conducted in more than 20 centers in five countries, the 30-day mortality in all 1128 patients currently entered into the trial is 1.2%. This is consistent with the results in the surgical arm of the Stent or Surgery (SoS) trial, where the 1-year mortality for about 500 CABG patients was 0.8% [6], emphasizing the remarkable safety and efficacy of CABG. Scientific Rationale for CABG in Multivessel and Left Main Stem Disease There is a strong scientific basis for CABG in multivessel and left main stem disease. This is summarized in the meta-analysis by Yusuf and colleagues [7] of seven randomized trials of CABG versus medical therapy, involving 2650 patients followed-up for 10 years, which was published in The Lancet in Although the trials are now outdated compared with current best surgical and medical therapy, they nevertheless established certain principles. The trials showed that there was a survival advantage and marked improvement in symptom relief in patients undergoing CABG who had left main stem disease or triple-vessel disease, especially when it involved proximal left anterior descending artery (LAD) disease, and that the benefits were magnified in patients with severe symptoms, a positive exercise electrocardiogram, or impaired left ventricular function, or a combination of these. Furthermore, the authors also made three important observations about CABG: 1. They concluded that the benefits of CABG in more extensive disease are underestimated for three reasons: the patients in the trials were predominantly low risk; the results were analyzed on an intention-to-treat basis, so that although 40% of the medical group had crossed over to CABG by 10 years, they were still analyzed as only having had medical therapy; and only 10% of surgical patients received an internal thoracic artery graft, which is now known to be the most important component of surgery. 2. They emphasized that there was no survival benefit for CABG in patients with single-vessel or double-vessel disease and normal left ventricular function. Let me repeat this, as it is vital to the understanding of the conduct of subsequent trials of PCI vs CABG. There was no survival benefit for CABG in patients with single-vessel or double-vessel disease and normal left ventricular function. Table 2. Current Coronary Artery Bypass Grafting Patient Characteristics Previous RCT (%) UK 2003 (%) Age (mean) 51 (7) 64 (9) Ejection fraction Left main disease vessel disease Occluded vessel(s) 30 Proximal LAD disease Urgent operation 30 IMA graft used RCT randomized controlled trial; UK United Kingdom; LAD, left anterior descending artery; IMA internal mammary artery. 3. They recommended that future trials of PCI and CABG should include a high proportion of patients for whom surgery is known to be superior to medical therapy; however, as we will see, this never happened. Characteristics of Patients Undergoing CABG Today The accompanying Table 2 shows that the characteristics of patients currently undergoing CABG are very different from what they were in those previous trials. Patients are now a mean of a decade older, with a higher proportion having impaired ventricular function, significant left main disease, true triple-vessel disease, and occluded vessels. More than 90% of patients have proximal LAD disease, and about one third of patients undergo an urgent operation. Most important, more than 90% of CABG patients now receive an internal thoracic artery graft. In other words, patients undergoing CABG today are those who are known to have the most prognostic benefit from surgery. Summary of 15 Randomized Trials of PCI Versus CABG in Multivessel Disease The accompanying Table 3 is a complex but important table that summarizes the 15 randomized trials of PCI (five of which included the use of a stent) versus CABG in so-called multivessel disease. The summary line in Table 3 shows a number of key factors about these trials: The trials involved almost 9000 patients but probably only around 5% of the total eligible population; There were no patients with left main stem stenosis; Only about one third of patients had true triplevessel disease; Only about 40% of patients had proximal LAD disease; and Most patients had an ejection fraction of more than.50. In summary, therefore, the key feature to realize is that the vast majority of these patients had single-vessel or

4 Ann Thorac Surg FERGUSON LECTURE TAGGART 2006;82: CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 1969 Table 3. Summary of 15 Randomized Controlled Trials of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Multivessel Disease Trial N Pop (%) Stent LMD (%) 3VD (%) Proximal LAD (%) EF.50 DM (%) IMA (%) RITA ERACI LAUSANNE GABI EAST CABRI MASS BARI TOULOSE SIMA 121? ERACI II AWESOME MASS II ARTS a SoS a SUMMARY % CABG (UK) a The 5% is estimated. Pop popliteal; LMD left main disease; 3VD three-vessel disease; LAD left anterior descending artery; EF ejection fraction; DM diabetes mellitus; IMA internal mammary artery; RITA Randomised Intervention Treatment of Angina; ERACI (II) Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease; GABI German Angioplasty Bypass Surgery Investigation; EAST Emory Angioplasty versus Surgery Trial; CABRI Coronary Angioplasty versus Bypass Revascularisation Investigation; BARI The Bypass Angioplasty Revascularization Investigation; SIMA Stenting versus Internal Mammary Artery; AWESOME Angina With Extremely Serious Operative Mortality Evaluation; MASS II Medicine, Angioplasty, or Surgery Study; ARTS Arterial Revascularization Therapies Study; SoS Stent or Surgery. double-vessel disease and normal left ventricular function, a population in whom it had already been clearly established that there was no prognostic benefit from surgery. The corollary is that the trials largely excluded those patients who are known to have prognostic benefit from surgery, including left main disease and true triplevessel disease, true proximal LAD disease, occluded vessels, and impaired ventricular function. Nevertheless, a meta-analysis of 13 of these trials by Hoffman and colleagues [8] showed that even in these low-risk patients, there was a small but statistically significant survival benefit for surgery (p 0.02; number needed to treat, 53) and a marked reduction in the need for reintervention (p 0.001; number needed to treat, 3). Another meta-analysis of those trials comparing CABG versus PCI where stents were used [9] found no difference in 1-year survival. This result was entirely predictable, however, because 60% of the patients had singlevessel or double-vessel disease and all had normal left ventricular function (ie, a population known to have no prognostic benefit from CABG); whereas, patients with known prognostic benefit (ie, those with left main disease, severe complex three-vessel disease, occluded vessels, and poor left ventricular function) were excluded. Indeed, although only 4% of the screened population were actually randomized (and were atypical of most CABG patients in the real world), these results have been used to justify PCI in all patients with multivessel disease. I think it is regrettable that the Journal of Thoracic and Cardiovascular Surgery published this meta-analysis without an accompanying editorial or commentary to indicate these very significant limitations. In the best-known comparison of PCI and CABG, Serruys and colleagues [10] recently published 5-year outcomes of the Arterial Revascularization Therapy Study (ARTS) in which 1200 patients were randomized to PCI with stents or CABG. There was no difference in 1-year or 5-year survival (mortality in both groups was 2.6% at 1 year and 8% at 5 years), but there was a marked reduction in the need for reintervention by a factor of three (30% versus 9%) in favor of CABG. Yet again, however, these results were entirely predictable, because 70% of the patients actually had single-vessel or doublevessel disease and all had normal left ventricular function (ie, yet another population in whom it was known that there was no prognostic benefit from surgery). Nevertheless, in the 208 diabetic patients in the ARTS trial, the risk of death was 8% for CABG and 13% for PCI, with respective rates of need for repeat revascularization of 10% and 43% [10]. In the second largest trial of these trials, the SoS trial, almost 1000 patients were randomized to either PCI with stents or CABG. Again, the vast majority of patients had single-vessel or double-vessel disease and normal left ventricular function. Nevertheless the 1-year mortality was 0.8% in the CABG group versus 2.5% in the SoS

5 1970 FERGUSON LECTURE TAGGART Ann Thorac Surg CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 2006;82: group, with respective rates of repeat revascularization of 6% and 21% [5]. Nonapplicability of These Trials to Clinical Practice In an article published in the British Medical Journal last year [11], Surgery is the best intervention for severe coronary artery disease, with reference to the applicability of these trials to real clinical practice, I wrote: By largely excluding patients with severe three vessel coronary artery disease, the trials were, in effect, inherently biased against the prognostic benefit of surgery. Subsequent reporting of these trials was misleading. Because the papers were styled and titled as trials of multi-vessel ischaemic heart disease, the highly unrepresentative nature of the patient populations was apparent only to expert readers who were prepared to pursue the small print. Accompanying editorials, invariably written by cardiologists, either ignored or fleetingly mentioned this fundamental limitation. PCI Is Not as Effective as CABG in the Real World If the 15 randomized trials do not support the efficacy of PCI versus CABG (except in very-low-risk patients), is there any evidence from the real world that PCI is as effective as CABG? The answer is a convincing No! In the New York Registry [12] of almost 60,000 patients with at least two-vessel disease undergoing CABG or PCI as an initial strategy, and propensity-matched for both cardiac and noncardiac comorbidity, CABG at 3 years had significantly reduced the risk of death for patients with two-vessel and three-vessel disease. For threevessel disease (including proximal LAD disease), mortality at 3 years was 10.7% of CABG patients versus 15.6% of PCI patients, with a hazard ratio for death with CABG versus PCI of 0.65 (95% confidence interval [CI], 0.56 to 0.74). Even for patients with two-vessel disease without proximal LAD disease, the hazard ratio for death with CABG versus PCI was 0.76 (95% CI, 0.6 to 0.96). Furthermore, the incidence of repeat revascularization was sevenfold higher within 3 years for PCI rather than CABG (35% versus 5%). Numerous other studies in the literature testify to the superior efficacy of CABG over PCI with respect to survival and reduced reintervention: In more than 6000 patients with severe coronary disease, Brener and colleagues [13] reported that that an initial strategy of PCI increased the 5-year mortality by a factor of 2.3 (95% CI, 1.9 to 2.9). Serruys own group [14] compared 409 propensity-matched patients undergoing PCI and 409 undergoing CABG for mainly two-vessel disease and reported a significant improvement in both absolute and event-free survival in favor of CABG. The authors concluded, after adjusting, stent was an independent predictor of higher mortality. There is similar evidence of the superior results of CABG in diabetic patients, where PCI increased the 5-year mortality up to fourfold in 2766 riskmatched diabetic patients [15] and the 2-year mortality up to fourfold in 800 diabetic patients [16]. Why PCI Will Never Match CABG in Multivessel Coronary Artery Disease An accompanying editorial [17] to the New York Registry [12] questioned why, in comparison with PCI, there is such a prognostic benefit with CABG. The answer is that CABG deals not only with the immediate culprit lesion, which can be of any complexity, but also deals with future culprit lesions because the bypass graft is to the mid or distal vessel. Furthermore, CABG offers more complete revascularization with more durable grafts (particularly internal thoracic arteries) and especially in complex disease or with small vessels. In contrast, PCI only deals with the immediate culprit lesion, assuming that this is suitable, and has no protective effect against failure of the initial procedure or the development of new lesions. CABG in Left Main Stem Stenosis Significant left main stenosis is present in 10% of all angiograms. CABG has been shown to improve life expectancy in patients with left main stem stenosis in 29 studies, including three randomized trials conducted between 1975 and The most definitive report on the benefits of CABG is that of the long-term Coronary Artery Surgery Study (CASS) experience [18] based on almost 1500 patients with a left main stenosis of more than 50%. On the basis of these results, the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines stated the benefit of surgery over medical treatment for patients with significant left main stenosis ( 50%) is little argued. The median survival for surgically treated patients is 13.3 years versus 6.6 years in medically treated patients [19]. With regard to PCI for left main stem stenosis, ACC/ AHA guidelines [20] stated that PCI for unprotected left main stenosis is a class III indication in virtually all patients, where a class III indication is defined as a condition for which there is evidence or general agreement that the procedure/treatment is not useful/effective and, in some cases, may be harmful. Anatomy of Left Main-Stem Stenosis The potential rationale for using PCI in left main-stem stenosis is that about one quarter of lesions are midshaft, with apparently normal proximal and distal segments [21] and may be considered suitable for PCI. In contrast, 40% of lesions are bifurcated (involving the distal, left main, and the origins of the LAD and circumflex), 25% are circular (with at least two narrowings), 9% are ostial, and 2% are occluded, with retrograde filling

6 Ann Thorac Surg FERGUSON LECTURE TAGGART 2006;82: CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 1971 Table 4. Stenting in Suitable Left Main Versus Coronary Artery Bypass Grafting in All Left Main Stem Stenosis In-hospital 1 2 Year Author (reference) Sites N Stent (%) Death (%) Revasc (%) Death (%) Revasc (%) Keeley [22] Tan (all) [23] ? Tan (low risk) [23] ? Takagi [24] Park [25] Brueren [26] Kelley [27] ? Summary 7 PCI trials CABG ONPUMP (2000 5) CABG OFFPUMP (2000 5) PCI percutaneous coronary intervention; CABG coronary artery bypass grafting. from collaterals from the right coronary artery. Whereas CABG can treat all left main stem stenosis regardless of specific anatomy, PCI requires suitable anatomy. In the accompanying Table 4, I have summarized the results of six studies of bare metal stenting in suitable left main stem stenosis [22 27]. These PCI trials were conducted in 35 sites around the world and involved 780 patients, of whom 88% received a stent. Note that with stenting, the in-hospital mortality was 6%, with a further 4% of patients requiring immediate revascularization. Even more worrying, however, was that the 1-year to 2-year mortality was 17%, and 29% of patients required repeat revascularization. In all of these studies, the authors emphasized the limitations of PCI and recommended that for most suitable patients, CABG offered a superior outcome in terms of survival and freedom from reintervention. In contrast, seven studies of on-pump CABG between 2000 and 2005, in 3293 patients, had a 3.4% in-hospital mortality for all patients, including a high proportion of urgent patients (DP Taggart, unpublished observations). Interestingly, in those same seven studies where CABG was performed as an off-pump procedure in 1225 patients with left main stem disease, the mortality was 1.1%. This probably reflects superior myocardial preservation with off-pump surgery [28], which mitigates the impaired myocardial protection with conventional cardioplegia in patients with significant left main stem stenosis. Drug-Eluting Versus Bare Metal Stents in Left Main Coronary Artery Stenosis Two groups of investigators [29, 30] have compared outcome with bare metal and drug-eluting stents in patients with unprotected left main stenosis (Table 5). Colombo and colleagues [29] compared 64 bare metal and 85 drug-eluting stents and reported at 6 months 4% mortality and 19% repeat revascularization with drugeluting stents. Serruys and colleagues [30] compared 86 bare metal and 95 drug-eluting stents and reported a 30-day mortality of 11% with drug-eluting stents but an 18-month mortality of 14%, with 24 % of patients having some major adverse cardiovascular event. Serruys and colleagues wrote: Table 5. Drug-Eluting Stents in Left Main Stem Stenosis Chieffo/Colombo Circ 2005 Valgimigli/Serruys Circ BMS 85 DES 86 BMS 95 DES 30 days Mortality (%) 7 11 Repeat revascularization (%) 2 0 MACE (%) months Mortality (%) 9 4 Repeat revascularization (%) MACE (%) months Mortality (%) Repeat revascularization (%) 23 6 MACE (%) BMS bare metal stents; DES drug-eluting stents; MACE major adverse cardiac events.

7 1972 FERGUSON LECTURE TAGGART Ann Thorac Surg CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 2006;82: Drug eluting stents are superior to bare metal stents in reducing major adverse cardiovascular events, but not 18 month mortality. Until new evidence is provided by randomised clinical trials directly comparing the surgical and percutaneous approaches, CABG should remain the preferred revascularisation treatment in good surgical candidates with left main coronary artery disease [30]. With all these studies consistently demonstrating marked superiority of CABG over PCI for left main stem disease, I am uncertain that randomized trials against stenting are currently justifiable or ethical. The basis for randomized trials is that there should be equipoise between treatments, and that clearly does not exist for PCI in comparison with CABG in patients with left main stenosis. Five Myths Concerning PCI and Drug-Eluting Stents If I have argued that there is little evidence for the efficacy for PCI in multivessel or left main disease in the real world in comparison with CABG, is there good evidence that PCI is much safer than CABG? PCI is certainly a less invasive procedure, but it still has significant risks: 1. Risk of myocardial infarction. A recent study of 37% of patients who had a troponin elevation after PCI found that in 28%, magnetic resonance imaging defined a mean loss of 6 grams of left ventricular muscle mass [31]. This actually amounts to about 5% of true left ventricular muscle mass and means that 10% of patients have a significant myocardial infarction with PCI. This almost certainly explains the frequently observed deterioration in ventricular function after repeated PCI interventions. 2. Risk of cognitive dysfunction. It is frequently stated that PCI avoids the cerebral dysfunction associated with CABG. However, two randomized trials (the SoS and the Bypass Angioplasty Revascularization Investigation [BARI]) showed no difference in neuropsychologic outcome 6 months, 1 year, or 5 years after PCI or CABG [32, 33]. 3. Risk of restenosis with drug-eluting stents. The introduction of drug-eluting stents was accompanied by numerous articles stating that they abolish restenosis. However, the true rates of restenosis with drug-eluting stents from 10% in the simplest lesions [34] to almost 30% in more complex lesions [35, 36]. 4. Do drug-eluting stents improve clinical outcome over bare metal stents? Two meta-analyses have been done of 11 randomized trials of drug-eluting stents versus bare metal stents [37, 38]. These trials involved almost 5000 patients, followed-up for 6 to 12 months, where coronary lesions were of intermediate length (9 to 15 mm) in medium sized vessels (2.6 to 3.0 mm) and excluded high-risk lesions (multivessel disease, small vessels, long lesions, diabetes mellitus, restenosis). Although a significant reduction was found in angiographic restenosis in these relatively low-risk coronary lesions with drug-eluting stents (9% versus 29%), there was no decrease in mortality (0.9% both groups) or myocardial infarction (2.7% versus 2.9%) at 1 year. This probably reflects the previous observation of the superiority of CABG over PCI [17] that stents can only deal with the immediate culprit lesion but do not protect against future lesions. 5. Late thrombosis with drug-eluting stents. Several studies have reported that even a year after drugeluting stent implantation, patients who stop dual antiplatelet medication are at risk of myocardial infarction, which is associated with a very high mortality [39 41]. The reason is that drug-eluting stents prevent reendothelialization of vessels, making the vessel more prone to thrombosis. Health Economic Issues From the health economic point of view, there are doubts about the real value of PCI. In a review published by the on behalf of the National Institute for Clinical Excellence (NICE) in the United Kingdom in 2004, health economists wrote: In the absence of substantive clinical evidence of the superiority of stenting with drug eluting stents over CABG (for 2 and 3 vessel disease), to encourage the widespread use of drug eluting stents will drive up the cost of stenting, and if allowed to displace CABG, reduce the gain in quality and possibly the duration of life arising from CABG in the long term [42]. Summary and Conclusions 1. PCI, used appropriately (including some subsets of multivessel disease and left main stem stenosis) can be a very effective and worthwhile intervention. My criticisms, however, are aimed at its increasing, inappropriate, and non-evidence-based use in the wider population of patients with multivessel disease and, increasingly, left main stem stenosis, despite strong evidence from randomized trials and large real-world registries that CABG is a more effective treatment in terms of survival and freedom from recurrent angina and reintervention. 2. Although randomized trials, registries, and guidelines all strongly favor CABG for most patients with left main stem disease, are randomized trials against PCI ethical or justifiable? 3. Why will PCI never match the results of CABG in multivessel or left main disease? As explained earlier, CABG deals with the initial coronary lesion of any complexity, is also prophylactic against future culprit lesions, and offers more complete and more durable revascularization. 4. Patients undergoing PCI for multivessel or left main disease should be informed that PCI as an initial strategy, rather than CABG, significantly reduces survival, even at 3 years, and increases the

8 Ann Thorac Surg FERGUSON LECTURE TAGGART 2006;82: CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 1973 Table 6. Current Cardiology Recommendations for Percutaneous Coronary Intervention Society Written by Recommendations for PCI ACC/AHA 2005 Circ 2006 ESC 2005 EHJ 2005 BCS 2006 Heart 2006 Summary 23 cardiologists 1 surgeon 46 cardiologists 0 surgeons 8 cardiologists 1 surgeon 77 cardiologists 2 surgeons Patients with 2 or 3 vessel disease who are otherwise eligible for CABG including diabetes SURGICAL OPINION NOT RECOMMENDED All patients except diabetics with multivessel disease, unprotected LM, chronic total occlusions SURGICAL OPINION NOT RECOMMENDED Patients to be fully involved in decisions... treatment options SURGICAL OPINION NOT RECOMMENDED IN EFFECT: Almost all patients can be treated by PCI without discussing or offering patient option of CABG ACC American College of Cardiology; AHA American Heart Association; ESC PCI percutaneous coronary intervention; CABG coronary artery bypass grafting; LM left main; ECS European Cardiology Society; BCS British Cardiovascular Society. risk of reintervention fourfold to sevenfold. With PCI, there is a 10% risk of significant myocardial infarction and no benefit in short-term or long-term cognitive outcome when compared with CABG. Finally, even with drug-eluting stents, the risk of restenosis is 10% to 30%, and there is a real risk of late thrombosis if antiplatelet medication is stopped. So why is PCI replacing CABG against best evidence? There are three reasons: 1. the cardiologist is the gatekeeper, and this may produce a conflict of interest in terms of selfreferral; 2. the disingenuous presentation and inappropriate application of results of randomized trials in highly select and atypical groups to the whole population; and 3. the result of what happens when evidence-based medicine is challenged by a multibillion dollar industry. Current Recommendations for PCI I have summarized the current guidelines for PCI of three prestigious societies from America [43], Europe [44] and Britain [1] (Table 6). It is noticeable that the writing committee for these guidelines include 77 cardiologists but only two surgeons, and the recommendations are largely based on the 15 randomized controlled trials of highly select patients to which I have already referred. Despite this, the recommendations of these three societies are essentially that most patients with multivessel disease should have PCI as an initial default strategy. None recommend that the patient even be offered the option of CABG or promote the concept of the multidisciplinary team. So What is the Best Management of the Patient With Multivessel or Left Main Disease? The Problem The problem is summarized by Dr Califf, Head of Interventional Cardiology at Duke University, in an editorial in JACC, Stenting or Surgery [45]. It is likely that most people undergoing coronary angiography are not told the entire story when a decision is made about undergoing PCI. He attributes this to conflicts of self-referral and financial incentives, and concludes, Without surgical opinion, the patient is in no position to have a rational input into the decision. The Solution Patients with multivessel disease should be treated by a multidisciplinary team. As I wrote in the British Medical Journal: The current tendency of some cardiologists to exclusively investigate and treat patients with severe multi-vessel disease without a surgical opinion ensures that the best and most balanced advice is unlikely to be consistently offered. Most importantly, by effectively denying patients the opportunity of making a fully informed choice, it falls far short of best practice [11]. The Mechanism to Effect Change The conventional approach is to effect change through education and debate. However, it is becoming increasingly clear that, for some of the reasons previously outlined, some cardiology practice no longer appears to based on best evidence. I believe that the predominant American, Asian, and European surgical societies should individually and collectively promote, in the public domain, that CABG is the best treatment for severe coronary disease and that patients should seek the advice of a surgeon. It is only by delivering this message directly to the public that there is a chance of redressing the balance and ensuring that patients at least have access to the best treatment. Furthermore, educating the public in this manner fits well with the STS mission statement to help cardiothoracic surgeons serve patients better while the medicolegal implications of such a recommendation may stop some of the worst PCI excesses. Finally, I believe that surgical societies should no longer provide a token surgeon on cardiology guidelines, they are hopelessly outgunned, and ineffectual against what are, in effect, exclusive cardiology dictates. If

9 1974 FERGUSON LECTURE TAGGART Ann Thorac Surg CABG IS SUPERIOR TO PCI FOR MULTIVESSEL AND LEFT MAIN STEM DISEASE 2006;82: surgical opinion is genuinely to be heard, there must be comparable numbers of surgeons on writing committees. Finishing With the Thoughts of Cardiologists Finally, if it appears that I am hostile to current cardiology practice or interventions, let me emphasize again that this is not the case. I repeat: PCI, used appropriately (including some subsets of multivessel disease and left main stem stenosis), is a very effective and worthwhile intervention. Accordingly, in a spirit of consensus and cooperation, I would like to finish my lecture by quoting some cardiologists. The great father of interventional cardiology, Andreas Gruntzig, who tragically died prematurely in a plane crash at the age of 46, stated in 1979, we estimate that only about 10 15% of candidates for bypass surgery have lesions suitable for this procedure (PCI). A prospective randomised trial will be necessary to evaluate the usefulness in comparison with surgical and medical management [46]. In The Lancet on January 7 of this year, the headline cover stated, In view of the survival benefits shown for coronary artery bypass grafting the real controversy is why patients with symptoms and anatomy known to benefit from the procedure are still submitted to percutaneous coronary intervention [47]. That this was written by three senior cardiologists begins to give some encouragement that perhaps the tide may, at last, be turning. I would like to thank the society, and in particular Dr Levitsky, for having given me the great honor and privilege of presenting the Ferguson Lecture. References 1. Dawkins KD, Gershlick T, de Belder M, et al; Joint Working Group on Percutaneous Coronary Intervention of the British Cardiovascular Intervention Society and the British Cardiac Society. 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