EXCEL Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization Gregg W. Stone MD Columbia University Medical Center The Cardiovascular Research Foundation

ACC/AHA Guidelines Post SYNTAX IIb Stenting of the LMCA as an alternative to CABG may be considered in pts with anatomic conditions that are associated with a low risk of PCI procedural complications and clinical conditions that predict an increased risk of adverse surgical outcomes IIb = “may or might be considered; may or might be reasonable; usefulness/effectiveness is unknown/unclear/uncertain or not well established” ACC/AHA 2009 Focused Updates for STEMI and PCI. Circulation 2009;120:2271–2306

MACCE to 3 Years Left Main Subset TAXUS (N=357) CABG (N=348) 20 40 P=0.20 26.8% Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 52 2-Year_Randomized_20090820.doc Exhibits 21 SYNTAX 3-Year Report_Randomized_12JUL10.doc exhibits 21 (KM overall rate), 22 (year 2-3) 22.3% 12 36 24 Months Since Allocation Serruys PW. TCT2010 Cumulative KM Event Rate ± 1.5 SE; ITT population

3-Year Outcomes: Left Main Subset PCI 0-1 years CABG 0-1 years PCI 1-2 years CABG 1-2 years PCI 2-3 years CABG 2-3 years P=0.60 P=0.64 P=0.02 P=0.14 P=0.004 P=0.20 P=0.80 26.8 22.3 20.0 14.3 13.0 11.7 8.4 7.3 6.9 4.0 4.1 3.7 4.1 1.2 Death/ CVA/MI Death CVA MI Repeat Revasc. MACCE ST/GO Serruys PW. TCT2010

MACCE to 3 Years by SYNTAX Score Tercile Left Main SYNTAX Score 33 TAXUS (N=135) CABG (N=149) CABG PCI P value Death 7.6% 13.4% 0.10 CVA 4.9% 1.6% 0.13 MI 6.1% 10.9% 0.18 Death, CVA or MI 15.7% 20.1% 0.34 Revasc. 9.2% 27.7% <0.001 Left Main Left Main Months Since Allocation Cumulative Event Rate (%) 12 24 40 20 30 10 36 P=0.003 37.3% 21.2% 3-Year_Randomized_SX 33+(Core)-LM(Site)_01JUL10.doc ex. 1 Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population

MACCE to 3 Years by SYNTAX Score Tercile Low to Intermediate Scores (0-32) TAXUS (N=221) CABG (N=196) CABG PCI P value Death 9.0% 3.7% 0.02 CVA 3.3% 0.9% 0.09 MI 2.6% 4.6% 0.33 Death, CVA or MI 13.2% 8.7% 0.12 Revasc. 13.7% 15.7% 0.61 Left Main Months Since Allocation Cumulative Event Rate (%) 12 24 40 20 30 10 36 P=0.45 23.2% Cumulative Event Rate (%) 20.5% 3-Year_Randomized_SX0-22(Core)-LM(Site)_01JUL10.doc ex. 1 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population

Do we really need another randomized trial of PCI vs Do we really need another randomized trial of PCI vs. CABG for LM disease? YES: SYNTAX leaves many questions unanswered SYNTAX suggests (but doesn’t prove) that: PCI and CABG for LM ds. have similar rates of death/MI/stroke PCI may be acceptable or superior for certain LM subsets Could the results be further improved with a better DES and optimal pharmacotherapy? What is the optimal approach to the distal bifurcation? Could IVUS and/or FFR improve outcomes?

EXCEL: Study Design 4100 pts with left main disease PCI (Xience Prime) SYNTAX score ≤32 Consensus agreement by heart team Yes (N=3100) @ 165 international sites No (N=1000) Enrollment registry R PCI (Xience Prime) (N=1550) CABG (N=1550) Clinical follow-up: 1 mo, 6 mo and yearly through 5 years

EXCEL: Inclusion Criteria Clinical and anatomic eligibility for both PCI and CABG by heart team consensus Silent ischemia, stable angina, unstable angina or recent MI Significant LM ds. by heart team consensus Angiographic DS ≥70%, or Angiographic DS ≥50% to <70% with a markedly positive noninvasive study, and/or IVUS MLA <6.0 mm2, and/or FFR <0.80

EXCEL: Principal Endpoints Primary endpoint: Death, MI, or stroke at a median follow-up of 3 years - Powered for sequential noninferiority and superiority testing Major secondary endpoints: Stroke at 30 days (powered for noninferiority testing of CABG vs. PCI) Unplanned repeat revascularization for ischemia at a median follow-up of 3 years (powered for noninferiority testing of PCI vs. CABG) Quality of life and cost-effectiveness assessments: At baseline, 1 month, 1 year, 3 years and 5 years

EXCEL: Organization (i) Academically driven study; 50% interventionalists, 50% cardiac surgeons Principal Investigators: - Interventional: Patrick W. Serruys, Gregg W. Stone - Surgical: A. Pieter Kappetein, Joseph F. Sabik Executive Operations Committee: - 4 principal investigators, Peter-Paul Kint, Martin B. Leon, Alexandra Lansky, Roxana Mehran, Marie-Angèle Morel, Chuck Simonton, David Taggart, Lynn Vandertie, Gerrit-Anne van Es, Marie-Claude Morice, Jessie Coe, Poornima Sood, Ali Akavand, Krishnankutty Sudhir Optimal Therapy Committee Chairs PCI: Martin B. Leon Surgery: David Taggart Medical: Bernard Gersh Sponsor: Abbott Vascular

EXCEL: Organization (ii) Countries and Country Leaders (PCI and CABG) United States: David Kandzari and John Puskas Europe (10): Marie-Claude Morice and David Taggart Brazil: Alex Abizaid and Luis Carlos Bento Sousa Argentina: Jorge Belardi and Daniel Navia Canada: Erick Schampaert and Marc Ruel S. Korea: Seung-Jung Park and Jay-Won Lee Australia: Ian Meredith and Julian Smith China: TBD Statistical Committee: Stuart Pocock, Chair QOL and Cost-Effectiveness Analysis: David J. Cohen Data Safety and Monitoring Board: Lars Wallentin, Chair Academic Research Organizations - Cardiovascular Research Foundation and Cardialysis

EXCEL: Status After 2 years of preparation the protocol and CRF are finalized ~160 sites from 17 countries have been chosen and are being initiated FDA and global regulatory submissions are ongoing The trial has begun: 16 pts have been enrolled!