Article

Clinical Implications of the SYNTAX Study

Abstract

Recent years have seen an ongoing debate as to whether coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) is the most appropriate revascularisation strategy for patients with coronary heart disease (CAD). The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) study was conducted with the intention of defining the specific roles of each therapy in the management of de novo three-vessel disease or left main CAD. Interim results after 12 months show that PCI leads to significantly higher rates of major adverse cardiac or cerebrovascular events compared with CABG (17.8 versus 12.4; p=0.002), largely owing to increased rates of repeat revascularisation. However, CABG was much more likely to lead to stroke. Interestingly, categorisation of patients by severity of CAD complexity according to the SYNTAX score has shown that there are certain patients in whom PCI can yield results that are comparable to, if not better than, those achieved with CABG. Careful clinical evaluation and comprehensive assessment of CAD severity, alongside application of the SYNTAX score, can aid practitioners in selecting the most suitable therapy for each individual CAD patient.

Disclosure: The authors have no conflicts of interest to declare.

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Citation:Interventional Cardiology 2009;4(1):48-52

Correspondence: Patrick W Serruys, Erasmus MC, Thoraxcentre, Kamer Ba583, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E: p.w.j.c.serruys@erasmusmc.nl

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Coronary artery disease (CAD) is the predominant cause of heart disease and the leading cause of death worldwide. In recent decades revolutionary treatments have been developed and ushered in for its management. Following its introduction in 1968, coronary artery bypass (CABG) surgery rapidly became established as the standard of care for treatment of CAD.1 In 1977, Andreas Gruntzig performed the first percutaneous coronary intervention (PCI), which was seen as an innovative non-surgical alternative to CABG.2 Since their inception, both techniques have undergone significant developments that have reduced rates of morbidity and mortality despite the increasing age and prevalence of co-morbidities in the patient population receiving revascularisation.3 Advances in cardiac surgery include off-pump CABG, enhanced myocardial preservation, improvements in anaesthesia, pre-operative risk assessment and post-operative care, and an increased use of arterial conduits, which have reduced the rate of graft occlusion.4–7 In patients treated with PCI, improvements in technology and antiplatelet therapy coupled with landmark studies8–10 have effectively led to the replacement of balloon angioplasty with coronary artery stenting, which is the current preferred method of PCI.

The selection of appropriate therapy for CAD has been the subject of continuing debate for many years. Several studies comparing the use of bypass surgery and coronary bare-metal stents (BMS) in patients with multivessel disease have revealed higher rates of repeat revascularisation at five years in patients treated with BMS, while those patients treated with CABG have higher rates of stroke.

Nevertheless, overall survival has been comparable between both groups.11–17 However, seminal improvements in treatment options have now rendered these studies historical in their applicability to contemporary practice. The introduction of drug-eluting stents (DES) has greatly enhanced the PCI approach to managing CAD, with demonstrated superiority in reducing restenosis over their bare-metal predecessors while maintaining similar rates of death and myocardial infarction (MI).18–21

These reductions in restenosis and re-intervention have also been reproduced in patients with multivesssel disease22,23 and left main disease,24–26 such that the use of PCI has expanded to the treatment of patients with severe CAD.27 Nevertheless, to date the use of PCI in this patient population has not been supported by adequate data from evidence-based medicine or sufficiently powered randomised clinical trials.27 Indeed, current guidelines state that CABG remains the gold standard and treatment of choice for patients with severe CAD, including three-vessel disease and left main CAD.28

The SYNTAX Study

The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) study was designed to assess the optimum revascularisation strategy for patients with de novo three-vessel or left main CAD.29 To avoid criticism that patients enrolled would be non-representative of real-world patient cohorts, the SYNTAX trial adopted an all-comers design in which all eligible patients with de novo three-vessel or left main CAD were included. Patients were consecutively enrolled at sites in 17 countries in Europe and the US. Evaluation by a local heart team consisting of both an interventional cardiologist and a cardiothoracic surgeon determined the eligibility of the patients for PCI and/or CABG using a number of baseline factors, including angiograms, demographic characteristics, the SYNTAX score (denoting coronary vasculature lesion complexity), the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the Parsonnet score (indicating surgical risk profile). Those amenable for treatment with both techniques were randomised to undergo treatment by either CABG or PCI using the TAXUS Express paclitaxel-eluting coronary stent system (Boston Scientific Corporation). Patients for whom only one of the two revascularisation techniques was suitable were allocated to a parallel nested registry to identify specific patient populations in which each technique would be inappropriate: the PCI registry (CABG-ineligible patients) and the CABG registry (PCI-ineligible patients).

Patient Characteristics

While the SYNTAX study examined only patients with left main and/or up to three-vessel CAD, this population was not necessarily a general representation of patients requiring intervention. Indeed, patients can present with a spectrum of complexities in their coronary vasculature and a range of severity in CAD.

Developments in PCI technique over the last two decades have led to a general consensus that one- and two-vessel disease can be treated by PCI, while the main debate has circled around the treatment of three-vessel disease and the main stem. Specifically, in the SYNTAX study the selection of a population of patients with left main and/or three-vessel disease allowed the trial investigators to directly compare the outcomes from PCI and surgery in this population of patients with severe CAD.

Of the initial 4,337 patients with previously untreated three-vessel and/or left main CAD, only 3,075 were deemed eligible following screening.30 Of these patients, 1,275 were eligible for only one of the treatment options: 1,077 were enrolled in the CABG registry and 198 in the PCI registry. The remaining 1,800 patients were randomised to undergo CABG (n=897) or PCI with DES (n=903). Baseline demographic and clinical characteristics were largely well-balanced between the two groups. The PCI group had a significantly larger proportion of patients with blood pressure of 130/80mmHg or higher, while the CABG group had a higher number of current smokers and a higher number of patients with elevated triglyceride levels (≥150mg/dl) and reduced high-density lipoprotein cholesterol levels (<40mg/dl for men, <50mg/dl for women). Left main disease was present in 38.8 and 39.5% of patients in the PCI and CABG groups, respectively. Similar percentages of patients were considered to be at high surgical risk in both treatment groups, as indicated by EuroSCORE values of 6 or more (24.9% in the CABG group and 24.7% in the PCI group; p=0.94) and a Parsonnet score of 15 or more (20.2 and 20.5%, respectively; p=0.87).

Raw SYNTAX scores related to the characteristics of coronary artery lesions were 29.1 and 28.4 for the CABG and PCI groups, respectively (p=0.19). Among all patients, 23.1% had total occlusion and 72.8% had a bifurcation lesion. Significantly, each patient on average received treatment for more than four clinically significant coronary lesions (mean: 4.4 for CABG, 4.3 for PCI).

One-year Interim Results

The primary end-point of the SYNTAX study was formed of multiple components, consisting of any major adverse cardiac or cerebrovascular event (MACCE), an assessment of the composite outcome of death, myocardial infarction (MI), stroke and repeat vascularisation within 12 months of randomisation. At 12 months, the PCI group had experienced a significantly higher MACCE rate than the CABG group (17.8 and 12.4%, respectively; p=0.002).30 An absolute difference of 5.5% between the primary composite MACCE end-points of the two groups indicated that the pre-defined criteria for non-inferiority were not met. This led study investigators to uphold CABG as the standard of care in patients with three-vessel or left main CAD.

The difference observed in the primary composite MACCE end-point was largely due to the significantly increased rate of repeat revascularisation at 12 months in patients in the PCI group compared with those in the CABG group (13.5 versus 5.9%; p<0.001). Notably, an examination of only the hard end-points of death, MI and stroke showed that CABG patients had a significantly higher rate of stroke than the PCI group at 12 months, despite the balance between treatment groups in terms of baseline characteristics (see Table 1). Cardiac causes of death were greater with PCI than with CABG (3.7 and 2.1%, respectively; p=0.05), although non-cardiac causes of death were higher with CABG than with PCI (1.4 and 0.7%, respectively; p=0.13). Similar rates were observed for symptomatic graft occlusion in the CABG group and stent thrombosis in the PCI group (p=0.89).

The cohort of patients in the randomised arm of the study encompassed a wide range of three-vessel disease and/or left main stem disease, and therefore analysis of this group en mass does not provide clinicians with the appropriate information to deal with the individual patients that they see on a day-to-day basis. Therefore, to improve the applicability of the trial’s results, the patient population was subdivided according to the degree of coronary vasculature lesion complexity using the SYNTAX score. In patients having CABG, the MACCE rate at 12 months was similar regardless of their scores (see Figure 1). By contrast, 23.4% of patients in the PCI group with high SYNTAX scores (≥33) experienced significantly increased MACCE rates compared with those with low (0–22, 13.6%; p=0.002) or intermediate (23–32, 16.7%; p=0.04) scores.30 It is clear from the 12-month data that those patients with a SYNTAX score below 23 have outcomes with PCI that are at least as good as those with CABG in terms of safety, mortaility and MI, justifying the use of PCI in this subgroup of patients. The performance of patients with an intermediate score depended on the underlying CAD: patients with multivessel disease and/or diabetes appeared to do better with surgery, while patients with main stem disease without diabetes had comparable outcomes with either treatment.31

Differential treatment-dependent results have also become apparent in subgroup analyses (see Figure 2).30 While the 12-month MACCE rate was similar between treatment groups among patients with left main CAD (15.8 and 13.7% for PCI and CABG, respectively), the significantly higher rate of repeat vascularisation among these patients when receiving PCI (11.8% versus 6.5% in the CABG group) was offset by a significantly higher rate of stroke among left main CAD patients treated with CABG (2.7% versus 0.3% for PCI). Interestingly, a post hoc analysis found that patients with both left main disease and two- or three-vessel disease had higher MACCE rates than those who had isolated left main disease or left main disease in combination with one-vessel disease.

Patients with three-vessel disease in the absence of left main disease in the PCI group experienced significantly increased rates of MACCE (19.2 versus 11.5%) and repeat revascularisation (14.6 versus 5.5%) compared with the CABG group. Since PCI did not meet the non-inferiority criteria against CABG, any information obtained from subgroup analyses can only be regarded as speculative or hypothesis-generating, and warrants further investigation in future studies.

Implications for Clinical Practice
Use of Evidence-based Medicine to Direct Therapeutic Procedures

The results of the SYNTAX study have a number of implications in therapy. When designing the study, interventional cardiologists had proposed using intensive post-procedural medications such as antiplatelets, angiotensin-converting (ACE) inhibitors, statins and beta-blockers. These are frequently administered following PCI, with well-established benefits.32 While this practice was upheld in the SYNTAX study, the same degree of intensive therapy was not practised in the CABG arm of the study. This minor variation in the standard of care between the two groups is not a new occurrence; in practice, this presents only a small difference as patients soon return to the care of a cardiologist after surgical intervention. The lower rate of stroke observed among the PCI group is attributed to the higher use of antiplatelet therapy in this cohort of patients following the medical procedure and its protective effects against thromboembolic events. It is therefore possible that this benefit could be extended to patients undergoing CABG if the use of additional antiplatelet drugs were adopted as the norm in practice. Moreover, it is necessary to consider that the greater invasiveness of CABG could also account for the higher rate of stroke; the clamping of the aorta and atrial fibrillation resulting from the insertion of cannulae in the left atrium can increase the risk of cerebral emboli. This risk could potentially be minimised with intensive medical therapy. Alternatives to the standard CABG operation, which is known to confer a 1–2% risk of stroke, have been proposed. There is emerging evidence that suggests the use of anaortic techniques – in which surgery is conducted without cardiopulmonary bypass or aortic manipulation – can significantly diminish the incidence of stroke associated with the surgical procedure.33–35

The SYNTAX Score

Developed in 2005, the primary goal of the SYNTAX score was to encourage interventional cardiologists and cardiothoracic surgeons to work together in assessing the complexities of each patient’s coronary vasculature to try and foresee and anticipate the risks involved with each procedure and, in doing so, to reach a consensus in selecting the most appropriate therapy. A number of pre-existing classification systems focusing on specific functional and anatomical parameters of coronary lesions were used to form a global classification scoring system, with a greater number of points awarded to more severe lesion characteristics, such as those located proximal to or at the main stem, total occlusions, bifurcations and trifurcations.36

The SYNTAX score is now available online for use in clinical practice, complete with tutorials and example calculations (www.syntaxscore.com). Indicative of the complexity of the CAD, the score can divide patient populations into terciles, as shown in the SYNTAX study. The division of low, intermediate and high terciles is specific to the patient population being assessed. In populations with a similar degree of complexity to that enrolled in the SYNTAX study, scores below 23 would direct clinicians to recommend PCI, scores between 23 and 32 would lean towards surgery and scores of 33 and above would strongly suggest surgery.30 In this study, the SYNTAX score was shown to be predictive of outcomes in patients undergoing PCI. Notably, patients in the PCI group with high SYNTAX scores experienced elevated overall rates not only for MACCE, but also for the composite components of death, stroke and MI, suggesting the avoidance of PCI in patients with high SYNTAX scores. An assessment of the SYNTAX score found acceptable core lab reproducibility with an impact on PCI outcomes at one year, although no effect on outcome was present one year following surgical revascularisation.37 Further validation of the score is needed in other patient populations, but it is likely that the SYNTAX scoring tool will prove useful in a wide range of patients with complex CAD, with gradual integration to become a regular instrument in clinical practice.

Patient Assessment, Patient Involvement and Practitioner Perspectives

The use of a specialist heart team to conduct a thorough evaluation of each patient’s clinical history, diagnostic angiogram and electrocardiogram in the SYNTAX study prior to randomisation was a necessary element to decide whether a patient could be appropriately revascularised by either PCI or CABG, or both. This approach is already commonly employed by state institutions across Europe, where the cardiothoracic surgeon and the interventional cardiologist collaborate to reach a conclusion. In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial,38 no significant differences in terms of cardiac death, MI or other MACCE were observed between patients with stable angina pectoris treated with PCI and those receiving optimal medical therapy. In light of these data, one would anticipate the involvement of non-invasive cardiologists in the screening and treatment of patients with CAD in the coming decade.

Greater involvement from patients through physician-provided information and education is also expected to affect the choice of procedure. Indeed, patient participation could greatly influence which treatment method to proceed with, especially if one considers the risk–benefit ratio. Moving away from societal pressures of cost-effectiveness, medicine has begun to focus on patient-centric evaluations of risk–benefit. Although study results show no significant difference in mortality, stroke or MI rates between PCI and CABG, there are significant differences between the long-term efficacy of the two treatments and recovery time. With PCI, recovery, ambulation and return to normal daily activity can be achieved within two weeks in the majority of patients; however, patients do have a risk of late stent thrombosis and a gradual waning of the effect of the DES, resulting in a minority experiencing restenosis requiring re-intervention. By comparison, CABG is much more invasive, with all the risks of trauma generally associated with surgery and a much longer recovery time, as well as an increased risk of stroke. However, the long-term effect of CABG is much more robust and persistent. Therefore, patients and physicians must consider all of these factors, weighing the early benefits against the long-term risks of each treatment and balancing the two options with respect to their lifestyle, quality of life and general condition.39

The Role of Percutaneous Coronary Intervention

During the run-in phase of the SYNTAX study, a website survey conducted in 100 centres across Europe and the US found that these centres had treated more than 12,000 patients with three-vessel disease (n=8,532) and left main CAD (n=3,540) within a designated three-month period.27 Approximately one-third of this population was treated using PCI, and the remaining two-thirds by surgery. The SYNTAX study now provides justification for the use of PCI in this patient population through evidence-based support, in that the use of PCI rather than surgery in three-vessel disease and left main CAD patients was, and continues to be, a valid practice decision.

The observed efficacy of PCI in patients with left main disease negates the original convention set by guidelines stating that lesions in the main stem should always be treated surgically.28 The concept that certain types of main stem CAD can be managed by PCI has very important implications. Knowing which population of patients with three-vessel disease can be treated with PCI is invaluable.40 Moreover, if a greater proportion of patients with three-vessel disease and/or left main CAD from the lower two terciles of the SYNTAX score receive PCI in lieu of CABG, these patients would benefit from not only a substantially lower risk of stroke, but also the potential of achieving revascularisation without needing to recover from a sternotomy.

Insights and Conclusions

Data from the two-, three- and five-year follow-ups of the SYNTAX study are awaited with interest. From the long-term follow-up of other randomised studies comparing coronary stenting and CABG in CAD, long-term survival and safety profiles remain similar between the two modalities.41,42 However, a slow and progressive erosion of the efficacy of PCI is evident over time, such that by comparison the rates of adverse cardiac and cerebrovascular events are much higher than those of CABG patients over the long term, driven by the need for increased rates of revascularisation.16,41,43 Drawing on the results of these previous studies, it is reasonable to expect similar results: a waning of the PCI effect requiring subsequent re-intervention, and persistence of surgical results.

For the practitioner, the most important message to take away from the SYNTAX study is that patients with three-vessel disease should no longer be treated using a generalised approach, but rather should undergo a careful clinical evaluation and thorough assessment of their coronary anatomy. The SYNTAX score can be used to aid the interventional cardiologist and cardiac surgeon as to which of PCI or CABG is more appropriate; however, all factors – including patient preference – need to be considered. The goal of therapy, whichever modality is chosen, is ultimately to confer the greatest benefit on the patient with the least amount of risk. This can be achieved through continued co-operation and communication between cardiac surgeons and cardiologists.

References

  1. Favaloro RG, Saphenous vein autograft replacement of severe segmental coronary artery occlusion: operative technique, Ann Thorac Surg, 1968;5(4):334–9.
    Crossref | PubMed
  2. Gruntzig AR, Senning A, Siegenthaler WE, Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty, N Engl J Med, 1979;301(2):61–8.
    Crossref | PubMed
  3. 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(14): e340–437.
    PubMed
  4. Buxton BF, Komeda M, Fuller JA, Gordon I, Bilateral internal thoracic artery grafting may improve outcome of coronary artery surgery. Risk-adjusted survival, Circulation, 1998;98(19 Suppl.):II1–6.
    PubMed
  5. Tavilla G, Kappetein AP, Braun J, et al., Long-term follow-up of coronary artery bypass grafting in three-vessel disease using exclusively pedicled bilateral internal thoracic and right gastroepiploic arteries, Ann Thorac Surg, 2004;77(3): 794–9, discussion 799.
    Crossref | PubMed
  6. Barner HB, Operative treatment of coronary atherosclerosis, Ann Thorac Surg, 2008;85(4):1473–82.
    Crossref | PubMed
  7. Janssen DP, Noyez L, Wouters C, Brouwer RM, Preoperative prediction of prolonged stay in the intensive care unit for coronary bypass surgery, Eur J Cardiothorac Surg, 2004;25(2):203–7.
    Crossref | PubMed
  8. Serruys PW, de Jaegere P, Kiemeneij F, et al., A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group, N Engl J Med, 1994;331(8):489–95.
    Crossref | PubMed
  9. Macaya C, Serruys PW, Ruygrok P, et al., Continued benefit of coronary stenting versus balloon angioplasty: one-year clinical follow-up of Benestent trial. Benestent Study Group, J Am Coll Cardiol, 1996;27(2):255–61.
    Crossref | PubMed
  10. Fischman DL, Leon MB, Baim DS, et al., A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators, N Engl J Med, 1994;331(8):496–501.
    Crossref | PubMed
  11. Serruys PW, Unger F, Sousa JE, et al., Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease, N Engl J Med, 2001;344(15):1117–24.
    Crossref | PubMed
  12. Rodriguez A, Bernardi V, Navia J, et al., Argentine Randomized Study: Coronary Angioplasty with Stenting versus Coronary Bypass Surgery in patients with Multiple- Vessel Disease (ERACI II): 30-day and one-year follow-up results. ERACI II Investigators, J Am Coll Cardiol, 2001;37(1): 51–8.
    Crossref | PubMed
  13. Morrison DA, Sethi G, Sacks J, et al., Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME), J Am Coll Cardiol, 2001;38(1):143–9.
    Crossref | PubMed
  14. Mercado N, Wijns W, Serruys PW, et al., One-year outcomes of coronary artery bypass graft surgery versus percutaneous coronary intervention with multiple stenting for multisystem disease: a meta-analysis of individual patient data from randomized clinical trials, J Thorac Cardiovasc Surg, 2005;130(2):512–19.
    Crossref | PubMed
  15. Booth J, Clayton T, Pepper J, et al., Randomized, controlled trial of coronary artery bypass surgery versus percutaneous coronary intervention in patients with multivessel coronary artery disease: six-year follow-up from the Stent or Surgery Trial (SoS), Circulation, 2008;118(4):381–8.
    Crossref | PubMed
  16. Daemen J, Boersma E, Flather M, et al., Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease: a meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials, Circulation, 2008;118(11):1146–54.
    Crossref | PubMed
  17. Hlatky MA, Boothroyd DB, Bravata DM, et al., Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials, Lancet, 2009;373(9670):1190–97.
    Crossref | PubMed
  18. Stettler C, Wandel S, Allemann S, et al., Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis, Lancet, 2007;370 (9591):937–48.
    Crossref | PubMed
  19. Kirtane AJ, Gupta A, Iyengar S, et al., Safety and efficacy of drug-eluting and bare metal stents: comprehensive metaanalysis of randomized trials and observational studies, Circulation, 2009;119(25):3198–3206.
    Crossref | PubMed
  20. Stone GW, Moses JW, Ellis SG, et al., Safety and Efficacy of Sirolimus- and Paclitaxel-Eluting Coronary Stents, N Engl J Med, 2007;356(10):998–1008.
    Crossref | PubMed
  21. Spaulding C, Daemen J, Boersma E, et al., A Pooled Analysis of Data Comparing Sirolimus-Eluting Stents with Bare-Metal Stents, N Engl J Med, 2007;356(10):989–97.
    Crossref | PubMed
  22. Serruys PW, Daemen J, Morice MC, et al., Three-year follow-up of the ARTS-II - sirolimus-eluting stents for the treatment of patients with multivessel coronary artery disease, Eurointervention, 2008;3:450–59.
    Crossref | PubMed
  23. Daemen J, Tsuchida K, Stefanini GG, et al., Two-year clinical follow-up of the unrestricted use of the paclitaxeleluting stent compared to the sirolimus-eluting stent as part of the Taxus-Stent Evaluated at Rotterdam Cardiology Hospital(T-SEARCH) registry, Eurointervention, 2006;2(3): 330–37.
    PubMed
  24. Arampatzis CA, Lemos PA, Tanabe K, et al., Effectiveness of sirolimus-eluting stent for treatment of left main coronary artery disease, Am J Cardiol, 2003;92(3):327–9.
    Crossref | PubMed
  25. Seung KB, Park DW, Kim YH, et al., Stents versus coronaryartery bypass grafting for left main coronary artery disease, N Engl J Med, 2008;358(17):1781–92.
    Crossref | PubMed
  26. Meliga E, Garcia-Garcia HM, Valgimigli M, et al., Longest Available Clinical Outcomes After Drug-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease: The DELFT (Drug Eluting stent for LeFT main) Registry, J Am Coll Cardiol, 2008;51(23):2212–19.
    Crossref | PubMed
  27. 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(4):486–91.
    Crossref | PubMed
  28. 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), J Am Coll Cardiol, 2006;47(1):216–35.
    PubMed
  29. Ong AT, Serruys PW, Mohr FW, et al., The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) study: design, rationale, and runin phase, Am Heart J, 2006;151(6):1194–1204.
    Crossref | PubMed
  30. Serruys PW, Morice MC, Kappetein AP, et al., Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease, N Engl J Med, 2009;360(10):961–72.
    Crossref | PubMed
  31. Garg S, Serruys P, Mediations on secondary revascularisation in the aftermath of the SYNTAX trial, Eurointervention, 2009;5(Suppl. D):D14–20.
    PubMed
  32. Steinhubl SR, Berger PB, Mann JT 3rd, et al., Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial, JAMA, 2002;288(19):2411–20.
    Crossref | PubMed
  33. Vallely MP, Potger K, McMillan D, et al., Anaortic techniques reduce neurological morbidity after off-pump coronary artery bypass surgery, Heart Lung Circ, 2008;17(4):299–304.
    Crossref | PubMed
  34. Calafiore AM, Di Mauro M, Teodori G, et al., Impact of aortic manipulation on incidence of cerebrovascular accidents after surgical myocardial revascularization, Ann Thorac Surg, 2002;73(5):1387–93.
    Crossref | PubMed
  35. Prapas SN, Panagiotopoulos IA, Hamed Abdelsalam A, et al., Predictors of prolonged mechanical ventilation following aorta no-touch off-pump coronary artery bypass surgery, Eur J Cardiothorac Surg, 2007;32(3):488–92.
    Crossref | PubMed
  36. Sianos G, Morel MA, Kappetein AP, et al., The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease, EuroIntervention, 2005;1:219–27.
    PubMed
  37. Serruys PW, Onuma Y, Garg S, et al., Assessment of the SYNTAX score in the Syntax study, EuroIntervention, 2009;5(1):50–56.
    Crossref | PubMed
  38. Boden WE, O’Rourke RA, Teo KK, et al., Impact of optimal medical therapy with or without percutaneous coronary intervention on long-term cardiovascular end points in patients with stable coronary artery disease (from the COURAGE Trial), Am J Cardiol, 2009;104(1):1–4.
    Crossref | PubMed
  39. Federspiel J, Stearns S, Van Domburg R, et al., Risk-Benefit Trade-offs in Revascularization Choices, Med Decis Making, 2009; in press.
  40. Serruys P, Garg S, Percutaneous Coronary Interventions for All Patients With Complex Coronary Artery Disease: Triple Vessel Disease or Left Main Coronary Artery Disease. Yes? No? Don’t Know?, Rev Esp Cardiol, 2009; in press.
    Crossref | PubMed
  41. Serruys PW, Ong AT, van Herwerden LA, et al., Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial, J Am Coll Cardiol, 2005;46(4):575–81.
    Crossref | PubMed
  42. Serruys P, Onuma Y, Garg S, et al., Five-year clinical outcomes of the arterial revascularisation therapies (ARTS-II) study of the sirolimus-eluting stent in the treatment of patients with multivessel de novo coronary artery lesions [abstract], Eurointervention, 2009;5(Suppl. E).
  43. Rodriguez AE, Baldi J, Fernandez Pereira C, et al., Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II), J Am Coll Cardiol, 2005;46(4):582–8.
    Crossref | PubMed