Nuevas evidencias en revascularización coronaria: SYNTAX-ASCERT. El debate continúa.

Transcription

1 XXXVIII Congreso Argentino de Cardiología Nuevas evidencias en revascularización coronaria: SYNTAX-ASCERT. El debate continúa. La visión del cardioangiólogo intervencionista Dr. Alfredo E. Rodriguez, PhD, MTSAC, FACC, FSCAI Director del Centro de Estudios en Cardiología Intervencionista CECI Jefe Cardiología Intervencionista Sanatorio Otamendi y Miroli, CABA, Argentina Sanatorio Las Lomas, San Isidro, Buenos Aires, Argentina Clinica IMA, Adrogué, Buenos Aires, Argentina IV Simposio TCT@CACI@SAC 5-6 de octubre, 2012 Sheraton Hotel & Convetion Center

2 February 2007 O.R. ORAR III Trial: Clinical Cases of Oral Rapamycin + BMS group Male 46 yrs HT DLP BMI>29 Smoker Previous MI with Primary PCI in RCA 2 years ago.

3 ULMD & PCI

4 ULMD & PCI OVERALL SURVIVAL OVERALL SURVIVAL P=0.91 BMS CABG P=0.26 DES CABG DEATH, MI and STROKE DEATH, MI and STROKE P=0.59 BMS CABG P=0.16 DES CABG TARGET VESSEL REVASCULARIZATION TARGET VESSEL REVASCULARIZATION P<0.001 BMS CABG P<0.001 DES CABG Park S, et al.n Engl J Med, 2008 DES vs CABG

5 ULMD & PCI Kaplan-Meier Curves for Outcome in Patients Who Underwent Stent Implantation With DES or Concurrent Bypass Surgery Park, D. W. et al. J Am Coll Cardiol 2010;0:j.jacc v

6 ULMD & PCI Syntax MACCE to 3 years in LM subgroups

7 ULMD & PCI Characteristics: 8 studies with 2905 patients (CABG n=1669, PCI n= 1236) 2 randomized studies. Follow Up 12 months.

8 ULMD & PCI DEATH

9 ULMD & PCI DEATH, MI & STROKE

10 ULMD & PCI D. Capodanno et al. J Am Coll Cardiol 2011;58:

11 ULMD & PCI D. Capodanno et al. J Am Coll Cardiol 2011;58:

12 ULMCA stenosis: PCI or CABG Four Randomized studies have compared the efficacy of PCI vs CABG for treatment of ULMCA stenosis: LE LE MANS (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: ) BOUDRIOT (Boudriot E, Thiele H, Walther T, et al. Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis. J Am Coll Cardiol 2011;57: ) SYNTAX (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: PRECOMBAT (Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med 2011;364: ) Any of them have power to detect differences in death/mi/cva

13 ULMCA stenosis: PCI or CABG RATIONALITY of ECCEL Trial o More than 2000 patients with ULMC stenosis and SYNTAX <33 are being assigned to CABG or PCI o Primary end point death/mi/cva at 3 years of FU o Secodary end points death/mi/cva and unplanned revascularization o Study powered for non inferiority and superiority testing.

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16 *TAXUS EXPRESS

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18 European Heart Journal (2011) 32, Years Clinical Outcome. 3-vessels, LM and Diabetes subgroups. CABG PC I

19 ULMD & PCI Increased rate of cardiac events at one, two, three and four years of follow-up in Syntax trial in both groups: DES and CABG. Rodriguez AE et al, World J Cardiol 2012,

20 Cumulative Event Rate (%) All-Cause Death to 4 Years CABG (N=897) TAXUS (N=903) 50 Before 1 year * 3.5% vs 4.4% P= years * 1.5% vs 1.9% P= years * 1.9% vs 2.6% P= years * 2.2% vs 3.2% P=0.22 P=0.048 CABG FU rate 91.3% Mortality 18.7% 25 PCI F-U rate 97.3% Mortality 11.1% 11.7% Drop out: 70 CABG pts, and 24 PCI pts 8.8% Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

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22 78% DES Weintraub WS et al, ASCERT trial, N Engl Med 2012

23 Weintraub WS et al, ASCERT trial, N Engl Med 2012

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25 SYNTAX: 3 Years Clinical Outcome. 3-vessels, LM and Diabetes subgroups 1- Are we going to far?? 2- Are we using wrong stent device?? 3- Are we selecting the wrong PCI strategy

26 SYNTAX: 3 Years Clinical Outcome. 3-vessels, LM and Diabetes subgroups Are we going to far?? Are we are using wrong stent device?? Are we selecting the wrong PCI strategy??

27 Freedom From Death (A) and from Death and Myocardial Infarction (B) Daemen et al. Circulation. 2008;118:

28 Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials Hlatky MA, Boothroyd DB, Bravata DM, Boersma E, Booth J, Brooks MM, Carrié D, Clayton TC, Danchin N, Flather M, Hamm CW, Hueb WA, Kähler J, Kelsey SF, King SB, Kosinski AS, Lopes N, McDonald KM, Rodriguez A, Serruys P, Sigwart U, Stables RH, Owens DK, Pocock SJ. Lancet Apr 4;373(9670):1190-7

29 Death among patients. Diabetes and group allocation Diabetics: Better outcome with CABG, more data is pending Non Diabetics: Game is Over!! Hlatky MA et al. Lancet Apr 4;373(9670):

30 SYNTAX: 3 Years Clinical Outcome. 3-vessels, LM and Diabetes subgroups Are we going to far?? Are we are using wrong stent device?? Are we selecting the wrong PCI strategy??

31 Results in Very Late Outcome of Patients with Multiple Vessel Disease Treated With Drug Eluting Stents, Bare Metal Stents or Coronary Bypass Surgery: Insights From Final Five Years Follow Up of ERACI III Study BACKGROUND ERACI III Registry compared previous randomized data of BMS and CABG (ERACI II) with a prospective registry in a similar cohort of patients treated with first DES designs: TAXUS Express (Boston Scientific) and Cypher ( Cordis and J&J). At one year of follow up patients treated with DES had a significant lower incidence of MACCE either compared to BMS or CABG ( EuroIntervention 2006;2:53). At three years, patients treated with DES had significant lower MACCE compared to BMS (p=0.035) driven by lower TVR, however, a trend to high rate of MI with DES was observed. MACCE rate compared to CABG was similar (Eur Heart J 2007;28:218).

32 ESC Congress 2010 Stockholm, Sweden

33 ORAR III trial. 3 years results AE Rodriguez, PW Serruys et al. Catheter Cardiovasc Interv Death MI Stroke TVR p=0.86 TLR p=0.84 TVF p= p= yr % OR OR OR OR DES DES DES DES

34 ORAR III trial. 3 years results AE Rodriguez, PW Serruys et al. Catheter Cardiovasc Interv Death MI Stroke p=0.07 TVR p=0.50 TLR p=0.27 TVF p= yrs 1 yr % OR OR OR OR DES DES DES DES

35 PCI and AMI EES (everolimus-eluting stents) PES (paclitaxel-eluting stents) SES (sirolimus-eluting stents) ZES (zotorolimus-eluting stents) BMS (Bare metal stents) Scanning Electron Micrographs (14 days). The lumens are clearly patent and struts are easily discerned underneath a thin neointimal surface. Among DES, there is less endothelial cell surface coverage in SES and PES stents compared with ZES and EES. The panel insets are representative images at higher magnification ( 200) from proximal and distal regions showing bare struts, surface thrombi, inflammatory cells, and endothelial cells. M Joner et al, J Am Coll Cardiol. 2008;52(5):

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40 Stent Thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis T. Palmerini, G. Biondi-Zoccai et al. Lancet 2012; 379:

41 SYNTAX: 3 Years Clinical Outcome. 3-vessels, LM and Diabetes subgroups Are we going to far?? Are we are using wrong stent device?? Are we selecting the wrong PCI strategy??

42 SYNTAX TRIAL Selection and Patient Randomization N Engl J Med Mar 5;360(10):961-72

43 SYNTAX TRIAL Selection and Patient Randomization N Engl J Med Mar 5;360(10):961-72

44 N Engl J Med Mar 5;360(10): SYNTAX TRIAL Revascularization technique

45 SYNTAX TRIAL Revascularization Technique & Results N Engl J Med Mar 5;360(10):961-72

46 SYNTAX TRIAL Revascularization Technique & Results N Engl J Med Mar 5;360(10):961-72

47 SYNTAX TRIAL Revascularization Technique & Results N Engl J Med Mar 5;360(10): more than four stent on average were implanted per patient...

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49 Proportions of study population according to tertiles of the classic SYNTAX score (A) and after reevaluation by FFR (B). 32% of patients moved from a higher-risk group to a lower-risk group as follows: 38% of the highest SS tertile moved to the medium- or lowest-risk FSS group, 59% of the medium-risk SS tertile moved to the lowest-risk FSS group. J Am Coll Cardiol 2011;58: % SYNTAX BAJO

50 Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease (ERACI): in-hospital results and 1-year follow-up. ERACI Group. Rodriguez A, Boullon F, Perez-Baliño N, Paviotti C, Liprandi MI, Palacios IF. METHODS. This trial included patients with multivessel coronary artery disease and clinical indication of myocardial revascularization in whom complete functional revascularization could be achieved by the treatment of coronary lesions amenable to both coronary angioplasty or bypass surgery. J Am Coll Cardiol Oct;22(4):

51 Conclusiones

52 COURAGE Trial Results Event PCI + OMT OMT P-value Death + MI 19% 18.5% 0.62 Incidence of Hospitalizations 12.4% 11.8% 0.56 Stroke 2.1% 1.8% 0.19 Revascularization 21% 33% < Freedom from Angina at 1 year 66% 58% < 0.01 Freedom from Angina at 3 years 72% 67% <0.01 Freedom from Angina at 5 years 74% 72% 0.35 Boden WE et al. N Engl J Med 2007

53 Ischemia reduction 5% Primary Endpoint: % with Ischemia Reduction 5% Myocardium (N=314) p=0.004 PCI + OMT (n=159) OMT (n=155) Shaw LA. Circulation 2008;117:

54 Chronic Coronary Disease and PCI Odds Ratios for Mortality in Individual Trials Comparing the PCI-Based Strategy With Medical Treatment Strategy Schomig, A. et al. J Am Coll Cardiol 2008;52: Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

55 Any Death

56 Freedom From MI

57 Freedom From Angina Circ Cardiovasc Interv 2012; 5:

58 Muchas Gracias!!!

59 Muchas Gracias!!!

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61 ULMD & PCI SUMMARY

62 7.4% of hard events atribuble to stent thrombosis (ARC definition)

63 ESC Congress 2010 Stockholm, Sweden

64 ULMD & PCI SUMMARY

65 Cumulative Event Rate (%) All-Cause Death to 4 Years CABG (N=897) TAXUS (N=903) 50 Before 1 year * 3.5% vs 4.4% P= years * 1.5% vs 1.9% P= years * 1.9% vs 2.6% P=0.32 CABG FU rate 91.3% Mortality 18.7% P=0.048 PCI F-U rate 97.3% Mortality 11.1% 3-4 years * 2.2% vs 3.2% P= Drop out: 70 CABG pts, and 24 PCI pts 11.7% 8.8% Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

66 Left Main Stenosis in Randomized Clinical Trials Reported by Centro de Estudios en Cardiología Intervencionista (CECI) ERACI II-ERACI III (1996/2004) ORAR I (2003/2004) ORAR II (2004/2005) ORAR III (2006/2007) JESTENT (2006/2008) EUCATAX (2007/2009)

67 ULMD & PCI CECI Reported Randomized Clinical Trials Clinical Presentation at CATH LAB Clinical presentation (%) N = 69 Stable Angina 24.6 Acute Coronary Syndrome(CCS) 71 Unstable angina (BC) 60.9 Acute Myocardial Infarction 10.1

68 ULMD & PCI CECI Reported Randomized Clinical Trials Baseline Angiographic Characteristics N = 69 Multiple Vessel Disease,% 84.1 Vessel treated per patient, n 1.25 Lesion treated per patient, n 1.32 N stent used per patient, n 1.36 N stent used involving LMD, n 78 BMS, % 53.9 DES, % 46.1

69 ULMD & PCI CECI Reported Randomized Clinical Trials Cumulative results at a mean of 2 yrs and 10 months of follow-up. Clinical Results % (n=69) Death 8.70 Acute Myocardial Infarction 7.25 Stroke 0.00 Target Lesion Revascularization 20.3 Target Vessel Revascularization 23.2 Major Adverse Cardiovascular Events (MACCE) 33.3

70 ULMD & PCI Baseline Clinical Characteristics N patients Age N: 203 pts / yrs >= 65 yrs 55.2% Male Gender 76.8% Hypertension 73.4% Dyslipemia 61.6% Chronic Renal Insufficiency 3.2% Cardiac Heart Failure 6.4% BMI> % Current smoker 20.2% Diabetes Mellitus 19.7% CECI ULMD Registry

71 ULMD & PCI CECI ULMD Registry BASELINE CHARACTERISTICS (cont) Multiple Vessel Disease 64.0% Lesions treated per patient /- 0.6 MIX treatment (DES and BMS) 8.9% Only DES treatment 21.7% Only BMS treatment 69.5% BMS placed 180 stents DES placed 70 stents Proximal and Mid LM Lesion 51.2% Distal LM Lesion 48.8%

72 ULMD & PCI Clinical Status at hospital admision Acute Coronary Syndromes 70.9% Stable Angina 19.7% Positive Test. Induced Ischemia 9.4% CECI ULMD Registry

73 ULMD & PCI Clinical Status at hospital admision Acute Coronary Syndromes 70.9% Stable Angina 19.7% Positive Test. Induced Ischemia 9.4% CECI ULMD Registry 43.1% 31.3% 25.7%

74 ULMD & PCI CECI ULMD Registry 6.4% 4.4% 0.5% 2.0% 20.7% 25.1% Follow-up (2 yrs 10 months) 6.4% 3.9% 0.5%

75 ULMD & PCI CECI ULMD Registry 13.1% 6.1% (104 pts) (99 pts) 4.8% p= % p= 0.07 p= % Death, MI and stroke involoved segment of Left Main

76 ULMD & PCI CECI ULMD Registry 19.2% 22.2% 3.0% (104 pts) (99 pts) 1.0% p= % p=0.60 p= % TVR involved segment of Left Main

77 ERACI II and ERACI III Study Population of ERACI Trials: ERACI I ERACI II ERACI III 748 pts Severe CAD (Jun 1998 to Dec 1990) 2759 pts Severe CAD (Sept 1996 to Nov 1998) 3103 pts Severe CAD (Jun 2002 to Decem 2004) 302 pts Randomizable 1076 pts Randomizable 2141 pts Severe Multiple Vessel CAD 127 pts Randomized (16,9%) 450 pts Randomized (8%) 446 pts Treated with DES (19.8%) POBA 63 pts CABG 64 pts PCI 225 pts CABG 225 pts 225 pts with DES (Cypher or Taxus) and signed inform consent (7,2%) Rodriguez et al, EuroInterv 2006 STUDY POPULATION ERACI III

78 Results in Very Late Outcome of Patients with Multiple Vessel Disease Treated With Drug Eluting Stents, Bare Metal Stents or Coronary Bypass Surgery: Insights From Final Five Years Follow Up of ERACI III Study BACKGROUND ERACI III Registry compared previous randomized data of BMS and CABG (ERACI II) with a prospective registry in a similar cohort of patients treated with first DES designs: TAXUS Express (Boston Scientific) and Cypher ( Cordis and J&J). At one year of follow up patients treated with DES had a significant lower incidence of MACCE either compared to BMS or CABG ( EuroIntervention 2006;2:53).

79 SYNTAX TRIAL Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, van den Brand M, Bass EJ, Van Dyck N, Leadley K, Dawkins KD, Mohr FW; for the SYNTAX investigators N Engl J Med Mar 5;360(10):961-72

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81 *TAXUS EXPRESS

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83 Rates of Clinical Outcome. 3 Years of SYNTAX CABG PC I European Heart Journal (2011) 32,

84 Patient Characteristics Randomized Cohort CABG N=897 TAXUS N=903 P value Age, mean ± SD (y) 65.0 ± ± Male, % BMI, mean ± SD 27.9 ± ± Diabetes, % Hypertension, % Hyperlipidemia, % Current smoker, % Prior MI, % Unstable angina, % Additive EuroSCORE, mean ± SD 3.8 ± ± Total Parsonnet score, mean ± SD 8.4 ± ±

85 Patient Characteristics Notable Differences PCI RCT + Registry Patient-based TAXUS RCT * (n=903) PCI Reg (n=192) Total SYNTAX Score 28.4 ± ± 12.3 Diffuse disease or sm. vessels, % Mean no. lesions, n VD only, % Left main, any, % Left Main only Left Main + 1 vessel Left Main + 2 vessel Left Main + 3 vessel Total occlusion, % Bifurcation, % Trifurcation, % Core lab-reported * For descriptive purposes only; no statistical comparisons done

86 Patient Characteristics (II) Notable Differences CABG RCT + Registry Patient-based CABG RCT * (n=897) CABG Reg (n=644) Total SYNTAX Score 24.8 ± ± 13.7 Diffuse disease or small vessels, % Number of lesions, mean ± SD 4.0 ± ± 1.9 3VD only, % Left main, any, % Left Main only Left Main + 1 vessel Left Main + 2 vessel Left Main + 3 vessel Total occlusion, % Bifurcation, % Trifurcation, %

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88 Left Main Stenosis in Randomized Clinical Trials Reported by Centro de Estudios en Cardiología Intervencionista (CECI) ERACI II-ERACI III (1996/2004) ORAR I (2003/2004) ORAR II (2004/2005) ORAR III (2006/2007) JESTENT (2006/2008) EUCATAX (2007/2009)

89 Complete revascularization PCI success PCI Outcomes 1149 patients total 46 (4%) procedure not attempted 27 (2%) no lesions crossed 1077 patients (94%) had PCI attempted 958/1077 patients had PCI clinical success (less 89%) 787 patients (69%) had 2 or 3 vessel ds. 590 pts (59%) received 1 stent 416 pts (41%) received 2 stents At least 371 of 787 pts (47%) with multivessel disease had incomplete revascularization

90 Role of PCI In Chronic Relationship to Optimal Treatment and CABG: Angina in Medical What Chronic Angina Means? Asymptomatic or Stable Angina patients with low area of myocardial at risk? Asymptomatic or Stable Angina with large area of Myocardial at risk? Unstable Angina in patients with chronic coronary heart disease?

91 Complete revascularization PCI success PCI Outcomes 1149 patients total 46 (4%) procedure not attempted 27 (2%) no lesions crossed 1077 patients (94%) had PCI attempted 14% PTCA only 86% stents 97% BMS 3% DES 958/1077 patients had PCI clinical success (less 89%) 787 patients (69%) had 2 or 3 vessel ds. 590 pts (59%) received 1 stent 416 pts (41%) received 2 stents At least 371 of 787 pts (47%) with multivessel disease had incomplete revascularization

92 Chronic Coronary Disease and PCI Odds Ratios for Cardiac Death in Individual Trials Comparing the PCI-Based Strategy With Medical Treatment Strategy Schomig, A. et al. J Am Coll Cardiol 2008;52: Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

93 Chronic Coronary Disease and PCI Odds Ratios for Nonfatal Myocardial Infarction in Individual Trials Comparing the PCI- Based Strategy With Medical Treatment Strategy Schomig, A. et al. J Am Coll Cardiol 2008;52: Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.

94 SYNTAX TRIAL Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, van den Brand M, Bass EJ, Van Dyck N, Leadley K, Dawkins KD, Mohr FW; for the SYNTAX investigators N Engl J Med Mar 5;360(10):961-72

95 ORAR III trial. 3 years results AE Rodriguez, PW Serruys et al. Catheter Cardiovasc Interv Death MI Stroke TVR p=0.86 TLR p=0.84 TVF p= p= yr % OR OR OR OR DES DES DES DES

96 ORAR III trial. 3 years results AE Rodriguez, PW Serruys et al. Catheter Cardiovasc Interv Death MI Stroke p=0.07 TVR p=0.50 TLR p=0.27 TVF p= yrs 1 yr % OR OR OR OR DES DES DES DES

97 ULMD & PCI Increased rate of cardiac events at one, two, three and four years of follow-up in Syntax trial in both groups: DES and CABG. Rodriguez A et al, World J Cardiol 2012, in press

98 ULMCA stenosis: PCI or CABG o In the study of Boudriot 201 pts were randomized to SES or CABG. o Primary end point of the study death/mi/tvr was not reached due high rate of TVR with SES (14% vs 5.9% ) o No differences in death (CABG 5% vs PCI 2.5%) and MI (CABG 3% vs PCI 3%)

99 ULMCA stenosis: PCI or CABG The PRECOMBAT randomized 600 patients to CABG or PCI Deat/MI/CVA/TVR at one year was 8.7% in PCI and 6.7% with CABG. The study was underpowered for primary endpoint.

100 ULMCA stenosis: PCI or CABG Rationality of EXCEL Trial : Why they dont included > 33 SYNTAX Score? Why they dont included patients with 3 vessels CAD? All findings from subgroups of SYNTAX Trial such as ULMCA, SYNTAX Score, 3 vessels CAD are non powered for primary end point and only hypothesis generating

101 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, II, MASS-II, and SoS Trials Joost Daemen, MD; Eric Boersma, PhD; Marcus Flather, MBBS; Jean Booth, MSc; Rod Stables, MA, DM, FRCP; Alfredo Rodriguez, MD; Gaston Rodriguez-Granillo, MD, PhD; Whady A. Hueb, MD; Pedro A. Lemos, MD, PhD; Patrick W. Serruys, MD, PhD Circulation. 2008;118:

102 Revascularization of the Diabetic Patient ARTS, ERACI II, MASS II, SoS Daemen et al. Circulation. 2008;118:

103 PCI in Chronic Angina HAS PROVEN Long Term Safety and Benefit Overall Survival by Randomized Treatment Hlatky M et al, The Lancet,2009

104 Survival by Treatment and Left Ventricular Function Hlatky MA et al. Lancet Apr 4;373(9670):

105 Survival by Treatment and Age Group Hlatky MA et al. Lancet Apr 4;373(9670):

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107 Rates of Clinical Outcome. 3 Years of SYNTAX CABG PC I European Heart Journal (2011) 32,

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109 Patients (%) ULMD & PCI CABG TAXUS* Subgroup MACCE Rates at 12 Months SYNTAX All LM N=705 LM isolated N=91 LM+1VD N=138 LM+2VD N=218 LM+3VD N=258 Comparisons for the LM and 3VD subgroups are observational only and hypothesis generating 3VD (All) N=1095 * TAXUS Express Stent

110 Patient Characteristics Randomized Cohort CABG N=897 TAXUS N=903 P value Age, mean ± SD (y) 65.0 ± ± Male, % BMI, mean ± SD 27.9 ± ± Diabetes, % Hypertension, % Hyperlipidemia, % Current smoker, % Prior MI, % Unstable angina, % Additive EuroSCORE, mean ± SD 3.8 ± ± Total Parsonnet score, mean ± SD 8.4 ± ±

111 Patient Characteristics Notable Differences PCI RCT + Registry Patient-based TAXUS RCT * (n=903) PCI Reg (n=192) Total SYNTAX Score 28.4 ± ± 12.3 Diffuse disease or sm. vessels, % Mean no. lesions, n VD only, % Left main, any, % Left Main only Left Main + 1 vessel Left Main + 2 vessel Left Main + 3 vessel Total occlusion, % Bifurcation, % Trifurcation, % Core lab-reported * For descriptive purposes only; no statistical comparisons done

112 ULMCA stenosis: PCI or CABG Four Randomized studies have compared the efficacy of PCI vs CABG for treatment of ULMCA stenosis: LE LE MANS (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: ) BOUDRIOT (Boudriot E, Thiele H, Walther T, et al. Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis. J Am Coll Cardiol 2011;57: ) SYNTAX (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: PRECOMBAT (Park SJ, Kim YH, Park DW, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med 2011;364: ) Any of them have power to detect differences in death/mi/cva

113 Left Main Stenosis in Randomized Clinical Trials Reported by Centro de Estudios en Cardiología Intervencionista (CECI) ERACI II-ERACI III (1996/2004) ORAR I (2003/2004) ORAR II (2004/2005) ORAR III (2006/2007) JESTENT (2006/2008) EUCATAX (2007/2009)

114 Cumulative Event Rate (%) All-Cause Death to 4 Years CABG (N=897) TAXUS (N=903) 50 Before 1 year * 3.5% vs 4.4% P= years * 1.5% vs 1.9% P= years * 1.9% vs 2.6% P= years * 2.2% vs 3.2% P=0.22 P= CABG FU rate 91.3% PCI F-U rate 97.3% Drop out: 70 CABG pts, and 24 PCI pts 11.7% 0 8.8% Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates ITT population

115 ULMD & PCI Increased rate of cardiac events at one, two, three and four years of follow-up in Syntax trial in both groups: DES and CABG. Rodriguez AE et al, World J Cardiol 2012,

116 ESC Congress 2010 Stockholm, Sweden

117 Patient Characteristics (II) Notable Differences CABG RCT + Registry Patient-based CABG RCT * (n=897) CABG Reg (n=644) Total SYNTAX Score 24.8 ± ± 13.7 Diffuse disease or small vessels, % Number of lesions, mean ± SD 4.0 ± ± 1.9 3VD only, % Left main, any, % Left Main only Left Main + 1 vessel Left Main + 2 vessel Left Main + 3 vessel Total occlusion, % Bifurcation, % Trifurcation, %

118 ULMD & PCI D. Capodanno et al. J Am Coll Cardiol 2011;58:

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120 ESC Congress 2010 Stockholm, Sweden

121 ESC Congress 2010 Stockholm, Sweden

122 One year Outcomes according to the SYNTAX SCORE A=Classic SYNTAX Score B=Functional SYNTAX Score J Am Coll Cardiol 2011;58:1211 8

123 Stent Thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis T. Palmerini, G. Biondi-Zoccai et al. Lancet 2012; 379:

124 ULMD & PCI Rodriguez et al, ERACI II. JACC 2001.

125 ULMD & PCI Rodriguez et al, ERACI II. JACC 2001.

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128 Functional SYNTAX Score for Risk Assessment in Multivessel Coronary Artery Disease Chang-Wook Nam, Fabio Mangiacapra, Robert Entjes, In-Sung Chung, Jan-Willem Sels, Pim A. L. Tonino, Bernard De Bruyne, Nico H. J. Pijls, William F. Fearon, on behalf of the FAME Study Investigators J Am Coll Cardiol 2011;58:1211 8