Management of left main coronary artery disease: CABG is still the best therapy

David P. Taggart
John Radcliffe Hospital, Oxford, UK

Address for correspondence:
Dr David P. Taggart
Professor of Cardiovascular Surgery, University of Oxford
Dept of Cardiac Surgery, John Radcliffe Hospital
Oxford, OX3 9DU, UK
Tel: +44-(0)1865-221121 Fax: +44-(0)1865-220244
Email: david.taggart@btinternet.com

Abstract
This article reviews the pathophysiology of left main stem stenosis and the rationale for coronary artery bypass graft (CABG) surgery and stenting. As the majority of left main stem stenoses are distal/bifurcation lesions (at very high risk of restenosis with stents) and the majority of patients also have multivessel coronary artery disease (for which CABG is already a superior therapy to stents), the result is that for most unprotected left main stem stenosis surgery remains the standard of care. In the absence of real clinical equipoise, the article questions the ethics of randomised trials for left main stem stenosis and strongly advocates that all patients requiring intervention should receive advice from a multidisciplinary team.

Introduction
Over the past decade, coronary artery bypass graft (CABG) surgery has generally been regarded as the 'gold standard' therapy for significant left main stem (LMS) stenosis because of the proven survival benefit. Indeed, recently updated ACC/AHA guidelines for CABG state that "the benefit of surgery over medical treatment in patients with significant LMS stenosis (greater than 50%) is little argued" [1]. Because percutaneous coronary intervention (PCI) has not been shown to improve clinical outcome over optimal medical therapy in any situation with stable coronary artery disease [2,3], it is counter-intuitive to believe that it will do so in LMS stenosis. Consequently, both ESC [4] and ACC/AHA [5,6] guidelines for PCI still recommend CABG for patients with LMS stenosis who are eligible surgical candidates. Nevertheless, on the basis of early results with drug eluting stents (DES) in small cohorts of selected patients with LMS stenosis, some cardiologists are debating whether it is now appropriate for DES to replace CABG completely [7]. Furthermore, a recent survey of current interventional practice in patients with LMS stenosis, reported that 29% of European patients and 18% of North American patients underwent PCI rather than CABG [8]. While PCI may have a role in patients with ostial LMS stenosis (see below) and has a crucial role in patients who are haemodynamically unstable or are poor candidates for CABG, this article questions whether there is adequate clinical evidence to support the use of stents in most elective patients with unprotected LMS disease.

Pathophysiology of LMS and implications for revascularization with stents or surgery
Significant LMS disease is defined as any lesion exceeding 50% of the vessel diameter. In a recent study, LMS stenosis was reported to be present in 4-6% of patients undergoing coronary angiography [9,10]. However, its incidence is even higher in patients undergoing CABG, being present in up to 30% of such patients [11]. Furthermore, its incidence appears to be increasing and in the UK the proportion of CABG patients with LMS stenosis increased from 15% to 30% in the past decade [11].

The proximal location of the left main coronary artery and its relatively large diameter make it, in theory, an attractive target for PCI. However, in reality, several anatomical features severely diminish the likelihood of a successful long-term outcome with PCI. Firstly, up to 90% of stenoses extend from the distal LMS artery into the proximal left anterior descending and/ or circumflex coronary arteries [12-19] and such bifurcating lesions are at notoriously high risk of restenosis [20-23]. Secondly, around half the lesions are calcified [9] which also reduces the chance of a successful outcome with PCI. Finally, up to 80% of patients with LMS also have multi-vessel coronary artery disease [12-19] where coronary revascularisation with CABG already offers a survival advantage [24-29]. This is because, in contrast to PCI where the short and long-term success is critically dependent on the precise anatomical location and complexity of the lesion, these features are of little relevance to CABG as the bypass grafts are to placed to the mid coronary arteries, thereby offering prophylaxis to whole territories of proximal myocardium.

Scientific rationale for CABG in LMS stenosis
Over the past three decades, several randomised trials [30] and prospective cohort studies [31] have consistently demonstrated a marked survival benefit of CABG over medical therapy in patients with LMS stenosis. While current medical and surgical therapies have improved significantly since these pivotal studies (e.g. greater use of aspirin, statins and arterial grafts), a meta-analysis of the RCTs demonstrated a two-thirds reduction in mortality with CABG at 5 years with the benefit persisting at 10 years [30]. However, the trials probably underestimated the real survival benefit of surgery for the following reasons:

• the patients were relatively low risk
• analysis on an intention-to-treat basis discounted the survival benefit accrued in around 40% of the patients allocated to medical therapy who eventually crossed over to CABG but were still analysed as having only received medical therapy
• only around 10% of patients allocated to CABG actually received an internal mammary artery (IMA) graft (the most important component of a CABG procedure) [30]

In the CASS registry of almost 1500 patients, followed for up to 16 years, the median survival was almost seven years longer in the CABG group (13.3 vs. 6.6 years) [31] leading the ACC/AHA guidelines to state that "the benefit of surgery over medical treatment in patients with significant LMS stenosis (greater than 50%) is little argued" [1].

The UK Society of Cardiothoracic Surgery database recently reported 3% mortality in all 5000 patients undergoing CABG for LMS stenosis in 2003, in contrast to a mortality of 1.8% in all 17,000 patients with no LMS stenosis [11]. However, it must be appreciated that the risks of CABG are even lower in low-risk populations e.g. the one-year mortality in 504 CABG patients in the SoS trial was 0.8% [32] and the 30-day mortality in 3105 patients in the ART trial was 1% [33]. Whether surgical results can be improved further with the use of off-pump CABG and composite arterial grafts based on bilateral IMA grafts [34], to simultaneously avoid the use of cardiopulmonary bypass and to permit a no-touch aortic technique (thereby reducing the risk of stroke), is the subject of ongoing trials.

PCI with bare metal stents and drug-eluting stents for LMS
The recognition that stents minimized the procedural complications of elastic recoil and vessel dissection associated with plain balloon angioplasty encouraged several investigators to use bare metal stents (BMS) initially, and then drug-eluting stents (DES) in patients with LMS stenosis. However, interpretation of the clinical outcome of these studies and their relevance to real world clinical practice is frequently hampered by:

• the lack of several pieces of vital data including what actual proportion of all LMS stenosis patients underwent PCI rather than CABG (as PCI required a "suitable" lesion)
• the proportion of PCI patients who were precluded from CABG because of sufficiently severe co-morbidity (and were therefore also high risk for PCI)
• the proportion of patients who had significant distal LMS and bifurcation lesions; and
• the proportion of patients who had multivessel coronary artery disease

Finally, the follow-up was relatively short term for most of these studies, rarely exceeding two years and frequently only around one year.

With regard to BMS, at least eight studies were conducted in over 1100 patients between 1999-2003 in several sites around the world. These studies are summarized elsewhere [35] but included an overall in-hospital mortality of 6% with a need for further immediate revascularisation averaging 4% (range: 0-20%). However, more worrying was the fact that two-year mortality averaged 17% (range: 3-31%) and the need for repeat revascularisation rate averaged 29% (range: 15% to 34%).

However, more favourable results have been reported in 'low risk' patients mainly typified by younger patients with good left ventricular function, predominantly ostial or mid shaft LMS lesions and a lower incidence of concomitant coronary artery disease. For example, the ULTIMA registry reported a one-year mortality of 3.4% and a repeat revascularization rate of 32% in 89 low-risk patients [36] while Silvestri et al. reported a one-year mortality of 7% and a repeat revascularization rate of 28% in 63 of 93 low-risk patients 'with no contraindications to surgery' [37]. In one of the largest reports to date, Park et al. reported a total mortality of 7.4% at three years in 270 patients and a repeat revascularization rate of 28% [38]. However, as stated earlier, it should be borne in mind that the risks of CABG would also be low in such low-risk populations, e.g. the one-year mortality in 504 CABG patients in the SoS trial was 0.8% [32].

The ability of DES to reduce restenosis has now encouraged their use in LMS stenosis and, to date, several groups have published results involving almost 600 patients [12-19]. Again, however, relevance to real clinical practice is hampered by lack of detail regarding eligibility criteria for PCI vs. CABG (with the exception of one study [19]), small individual patient numbers (50-130 per study), limited clinical follow-up (most less than a year) and, with the exception of one study [15], incomplete or limited angiographic determination of the true incidence of restenosis. Considering that up to 94% of patients had significant distal or bifurcation LMS stenosis and 37-100% also had significant coronary artery disease, the average in-hospital mortality of 2.4% (range 0-11%) with an average immediate repeat revascularisation rate of 2% (range 0-6%) appears encouraging. However, at a mean follow-up of less than a year (range 6-18 months) mortality had increased to 7% (range 0-14%) and repeat revascularisation averaged 13% (range from 2-38%).

It is of particular note that while Park's group reported no deaths in 116 LMS patients at 18 months [13,17], they documented significant restenosis in 13% of the 85% of patients who underwent angiography at six months. It should be noted that in the only study with complete angiographic follow-up - at both three and nine months - Price and colleagues reported that the restenosis rate increased from 34% to 44% [15]. This difference in rates of restenosis probably reflects not only different patient populations and the duration and completeness of angiographic follow-up but, most importantly, the frequency of distal and bifurcation LMS stenosis. Serruys' group have again emphasised the crucial impact of distal LMS stenosis in predicting adverse outcomes with an almost three-fold increase in patients with distal LMS stenosis (30%) compared to those without (11%) at a median of 18 months [23]. In addition, as restenosis is frequently asymptomatic [15,19], it is uncertain how often or for how long surveillance angiography is necessary, with its associated financial implications.

LMS lesions potentially suitable for PCI
A recent multicentre retrospective registry of 147 patients with nonbifurcation LMS reported that PCI appears to be safe and effective. Restenosis rates were <1% at 6-month angiographic follow-up, major adverse clinical event rates were 7%, and at a median follow-up of around 2½ years cumulative cardiac mortality was 2.7% [39]. However, the authors reported that there were four late unexplained deaths raising the possibility of late stent thrombosis (see below).

Risk of stent thrombosis
A further consideration is that stent thrombosis appears to be a potentially important limitation of DES associated with an increased risk of myocardial infarction of 65-70% and of mortality of 25-45% [40-44]. The most likely mechanism is impaired endothelialisation leaving a potentially prothrombotic substrate within the vessel and necessitating prolonged dual antiplatelet medication with aspirin and clopidogrel for at least a year, despite its potential for increased bleeding complications and associated cost implications [45]. While the precise incidence of thrombosis associated with DES is unknown, in 'offlabel' use (and depending on the complexity of the lesion and other patient co-morbidities), the annual risk is estimated at between 1% and 5% and is 'associated with increased risks of both early and late stent thrombosis, as well as death or myocardial infarction' [46]. Health economists have repeatedly questioned the cost-effectiveness of stenting in multi-vessel coronary artery disease and the same uncertainties will almost certainly apply to LMS stenosis [47-49].

In view of continuing mortality and high repeat rates of revascularisation, these studies of both BMS and DES largely support the hypothesis that for the majority of surgically eligible patients, CABG offers a superior outcome in terms of survival and freedom from reintervention as reflected in European [4] and North American [5,6] guidelines for PCI.

Current comparisons of PCI and CABG for LMS stenosis
Although several trials of PCI vs. DES are underway (including the SYNTAX (which has now completed enrolment) only the LEMANS trial has reported results [50]. This randomised trial of 52 PCI and 53 CABG patients with LMS stenosis reported similar major adverse cardiac events (MACE) at 12 months by which time 15% of PCI patients had undergone further interventions [50]. However, as only 72% of the CABG group received an internal mammary artery graft and there was a relatively high mortality in this low-risk group, this questions the standard of surgery in that trial.

Three groups have reported registry outcomes for LMS stenosis for patients undergoing CABG or PCI with DES [16,18,19]. In the Bologna Registry [19], at a median followup of 14 months, the overall mortality was respectively 12% and 13% in 154 CABG and 157 PCI patients (but 3% respectively in good risk patients), with respective rates of repeat revascularisation of 3% and 26%. In an Italian Registry [16], there was no difference in one-year mortality after adjustment for baseline characteristics in 107 PCI and 142 CABG patients (who were significantly older with a higher proportion of renal failure (8% vs. 2%)). Crucially, however, the need for repeat revascularisation was 20% for PCI and 4% for CABG patients. Lee and colleagues reported the six-month outcome in 50 PCI and 123 CABG patients with LMS stenosis but the small numbers and short follow-up make the data difficult to interpret [18].

The justification for randomised trials of PCI vs. CABG with LMS stenosis can be debated, in the absence of real clinical equipoise between the interventions for most patients (i.e. substantial uncertainty over the risks and benefits of each therapy) [51]. However, it is vital that where such trials are conducted, they are powered sufficiently to evaluate mortality as well as other clinically important differences (to avoid an erroneous conclusion that the two interventions are equally effective). They should also include at least mediumterm follow-up of at least five years (as the benefits of surgery accrue with time) and they should maintain a registry of all potentially eligible patients not entered into the trials (to reflect real clinical practice).

Conclusions
As most patients with LMS stenosis have distal/bifurcation disease and simultaneous multi-vessel coronary artery disease (which both mitigate against long term success with PCI), then in the absence of contraindications to surgery, CABG is still the 'gold standard' for most patients because of its substantial survival advantage and freedom from repeat intervention. PCI may be considered in those patients with isolated LMS stenosis not involving the bifurcation, those ineligible for CABG because of significant concomitant co-morbidity or in appropriately informed patients who refuse surgery.

Finally, consultation by a multidisciplinary team (MDT) - including a non-interventional as well as an interventional cardiologist and a cardiac surgeon - is essential to ensure that the patient receives the most balanced advice [29,52]. An MDT is vital to ensure that the patient understands that due to the greater potential lethality of LMS stenosis, the choice of surgery or PCI has significant implications for longevity and the risk of repeat reintervention. It should be emphasised that apparent satisfactory short-term outcomes of PCI are less favourable even within a year and that significant uncertainties about its reliability and durability over the longer term mandate surveillance angiography and should be weighed against the proven survival benefits of surgery.




References

1. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 2004;110:e340-437.
2. Katritsis DG, Ioannidis JP. Percutaneous coronary intervention versus conservative therapy in nonacute coronary artery disease: a meta-analysis. Circulation 2005;111:2906-12.
3. Boden WE, O'Rourke RA, Teo KK, et al. COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-16.
4. Silber S, Albertsson P, Aviles FF, et al. Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 2005;26:804-47.
5. Smith SC Jr, Dove JT, Jacobs AK, et al. American Heart Association Task Force on Practice Guidelines. Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines)- -executive summary. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty). J Am Coll Cardiol 2001;37:2215-39.
6. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, et al. ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). Circulation 2006;113:156-75.
7. Baim DS, Mauri L, Cutlip DC. Drug-eluting stenting for unprotected left main coronary artery disease: are we ready to replace bypass surgery? J Am Coll Cardiol 2006;47:878-81.
8. Kappetein AP, Dawkins KD, Mohr FW, et al. Current percutaneous coronary intervention and coronary artery bypass grafting practices for three-vessel and left main coronary artery disease. Insights from the SYNTAX run-in phase. Eur J Cardiothorac Surg 2006;29:486-91.
9. Ragosta M, Dee S, Sarembock IJ, et al. Prevalence of unfavorable angiographic characteristics for percutaneous intervention in patients with unprotected left main coronary artery disease. Catheter Cardiovasc Interv 2006;68:357-62.
10. Jonsson A, Ivert T, Svane B, et al. Classification of left main coronary obstruction - feasibility of surgical angioplasty and survival after coronary artery bypass surgery. Cardiovasc Surg 2003;11:497-505.
11. Keogh BE, Kinsman R. Fifth national adult cardiac surgical database report 2003. Dendrite Clinical Systems (Henley-on Thames, Oxfordshire, UK) 2004.
12. de Lezo JS, Medina A, Pan M, et al. Rapamycin-eluting stents for the treatment of unprotected left main coronary disease. Am Heart J 2004;148:481-5.
13. Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis: comparison with bare metal stent implantation. J Am Coll Cardiol 2005;45:351-6.
14. Valgimigli M, van Mieghem CA, Ong AT, et al. Short- and longterm clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: insights from the Rapamycin-Eluting and Taxus Stent Evaluated At Rotterdam Cardiology Hospital registries (RESEARCH and T-SEARCH). Circulation 2005;111:1383-9.
15. Price MJ, Cristea E, Sawhney N, et al. Serial angiographic follow-up of sirolimus-eluting stents for unprotected left main coronary artery revascularization. J Am Coll Cardiol 2006;47:871-7.
16. Chieffo A, Morici N, Maisano F, et al. Percutaneous treatment with drugeluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience. Circulation 2006;113:2542-7.
17. Kim YH, Park SW, Hong MK, et al. Comparison of simple and complex stenting techniques in the treatment of unprotected left main coronary artery bifurcation stenosis. Am J Cardiol 2006;97:1597-601.
18. Lee MS, Kapoor N, Jamal F, et al. Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2006;47:864-70.
19. Palmerini T, Marzocchi A, Marrozzini C, et al. Comparison between coronary angioplasty and coronary bypass surgery for the treatment of unprotected left main coronary artery stenosis (the Bologna Registry). Am J Cardiol 2006;98:54-9.
20. Tanabe K, Hoye A, Lemos PA, et al. Restenosis rates following bifurcation stenting with sirolimus-eluting stents for de novo narrowings. Am J Cardiol 2004;94:115-8.
21. Lemos PA, Hoye A, Goedhart D, et al. Clinical, angiographic, and procedural predictors of angiographic restenosis after sirolimus-eluting stent implantation in complex patients: an evaluation from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) study. Circulation 2004;109:1366-70.
22. Hoye A, Iakovou I, Ge L, et al. Long-term outcomes after stenting of bifurcation lesions with the "crush" technique: predictors of an adverse outcome. J Am Coll Cardiol 2006;47:1949-58.
23. Valgimigli M, Malagutti P, Rodriguez-Granillo GA, et al. Distal left main coronary disease is a major predictor of outcome in patients undergoing percutaneous intervention in the drug-eluting stent era: an integrated clinical and angiographic analysis based on the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) registries. J Am Coll Cardiol 2006;47:1530-7.
24. Hoffman SN, TenBrook JA, Wolf MP, et al. A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes. J Am Coll Cardiol 2003;41:1293-304.
25. Brener SJ, Lytle BW, Casserly IP, et al. Propensity analysis of long-term survival after surgical or percutaneous revascularization in patients with multivessel coronary artery disease and high-risk features. Circulation 2004;109:2290-5.
26. 26. Hannan EL, Racz MJ, Walford G, et al. Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005;352:2174-83.
27. Malenka DJ, Leavitt BJ, Hearne MJ, et al. Comparing long-term survival of patients with multivessel coronary disease after CABG or PCI: analysis of BARI-like patients in northern New England. Circulation 2005;112:I371-6.
28. Smith PK, Califf RM, Tuttle RH, et al. Selection of surgical or percutaneous coronary intervention provides differential longevity benefit. Ann Thorac Surg 2006;82:1420-8.
29. Taggart DP. Surgery is the best intervention for severe coronary artery disease. BMJ 2005;330:785-6.
30. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994;344:563-70.
31. Caracciolo EA, Davis KB, Sopko G, et al. Comparison of surgical and medical group survival in patients with left main equivalent coronary artery disease. Long-term CASS experience. Circulation 1995;91:2335-44.
32. Zhang Z, Mahoney EM, Spertus JA, et al. The impact of age on outcomes after coronary artery bypass surgery versus stent-assisted percutaneous coronary intervention: one-year results from the Stent or Surgery (SoS) trial. Am Heart J 2006 Dec;152:1153-60.
33. Taggart DP, Lees B, Gray A, et al. Protocol for the Arterial Revascularisation Trial (ART). A randomised trial to compare survival following bilateral versus single internal mammary grafting in coronary revascularisation [ISRCTN46552265]. Trials. 2006;7:7.
34. Taggart DP. Thomas B. Ferguson Lecture. Coronary artery bypass grafting is still the best treatment for multivessel and left main disease, but patients need to know. Ann Thorac Surg 2006; 82:1966-75.
35. Tan WA, Tamai H, Park SJ, et al. Long-term clinical outcomes after unprotected left main trunk percutaneous revascularization in 279 patients. Circulation 2001;104:1609-14.
36. Silvestri M, Barragan P, Sainsous J, et al. Unprotected left main coronary artery stenting: immediate and medium-term outcomes of 140 elective procedures. J Am Coll Cardiol 2000;35:1543-50.
37. Park SJ, Park SW, Hong MK, et al. Long-term (three-year) outcomes after stenting of unprotected left main coronary artery stenosis in patients with normal left ventricular function. Am J Cardiol 2003;91:12-6.
38. Chieffo A, Park SJ, Valgimigli M, et al. Favorable long-term outcome after drugeluting stent implantation in nonbifurcation lesions that involve unprotected left main coronary artery. A multicenter registry. Circulation 2007;116:158-62.
39. Tung R, Kaul S, Diamond GA, et al. Narrative review: drug-eluting stents for the management of restenosis: a critical appraisal of the evidence. Ann Intern Med 2006;144:913-9.
40. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-30.
41. Camenzind E, Gabriel Steg P, Wijns W. Stent Thrombosis Late After Implantation of First-Generation Drug-Eluting Stents. A Cause for Concern. Circulation 2007;115:1440-55.
42. Lagerqvist B, James SK, Stenestrand U, et al. Long-term outcomes with Drug-Eluting Stents versus Bare-Metal Stents in Sweden. N Engl J Med 2007;356:1009-19.
43. Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006;48:2584-91.
44. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol 2007;49:734-9.
45. Farb A, Boam MS. Stent thrombosis redux-the FDA perspective. N Engl J Med 2007;356:984-7.
46. Hill R, Bagust A, Bakhai A, et al. Coronary artery stents: a rapid systematic review and economic evaluation. Health Technol Assess 2004;8:1-242.
47. Kaiser C, Brunner-La Rocca HP, Buser PT, et al. Incremental costeffectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial (BASKET). Lancet 2005;366:921-9.
48. Griffin SC, Barber JA, Manca A, et al. Cost effectiveness of clinically appropriate decisions on alternative treatments for angina pectoris: prospective observational study. BMJ. 2007;334:624.
49. Buszman PE, Kiesz SR, Bochenek A, et al. Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization. J Am Coll Cardiol 2008;51:538-45.
50. Taggart DP. Coronary-artery stents. N Engl J Med 2006;354:2076-8.
51. Taggart DP. Coronary revascularisation. BMJ 2007;334:593-4.

06-2008 BUY1163660/JB3272/MB002753CMC Int'l English 16th Edition

 

Source: C2I2, Volume VI, Issue 1, 2008

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