A Pooled Analysis From SYNTAX and BEST Randomized trials 3:15-3:25 PM, Monday, February 20, 2017 Regency Ballroom PCI and CABG for Multivessel Coronary Disease: A Pooled Analysis From SYNTAX and BEST Randomized trials Patrick W. Serruys, MD, PhD Yohei Sotomi Academic Medical Center, the Netherlands Yoshinobu Onuma Erasmus MC, the Netherlands Professor of Cardiology of Imperial College Emeritus Professor of Cardiology Dr. Honoris Causa in Biomedical Engineering

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Grant/Research Support Consulting Fees/Honoraria Abbott AstraZeneca Biotronik Boston scientific Cardialysis GLG Research Medtronic Sinomedical Sciences Technology Société Europa Digital Publishing, Stentys France Svelte Medical Systems Volcano Qualimed St. Jude Medical Xeltis

European Guidelines for Myocardial Revascularization Windecker S, et al. Eur Heart J 2014

SYNTAX n=1800 Pooled data n=2680 BEST n=880 Collaborative works between Rotterdam and Seoul on the multivessel coronary disease SYNTAX n=1800 Pooled data n=2680 BEST n=880 LM or 3VD 2VD or 3VD Rotterdam Seoul

CABG, as compared with PCI with drug-eluting stents, significantly reduced the long-term risk of mortality in nondiabetic patients with multivessel CAD. J Am Coll Cardiol 2016;68:29–36

All-cause death CABG, as compared with PCI with drug-eluting stents, significantly reduced the long-term risk of mortality in nondiabetic patients with multivessel CAD. All-cause death All-cause death J Am Coll Cardiol 2016;68:29–36

In patients with multivessel disease with proximal LAD involvement, CABG is associated with lower rates of the safety composite endpoint of death, MI or stroke as compared with PCI with drug-eluting stents at 5 years of follow-up (number needed to treat=21). Heart 2016;0:1–6. doi:10.1136/heartjnl-2016-309720

Heart 2016;0:1–6. doi:10.1136/heartjnl-2016-309720 In MVD patients with proximal LAD involvement CABG was associated with a significantly lower rate of the composite endpoint of all-cause death, MI or stroke (primary endpoint). The rates of cardiac death, MI, all-cause revascularization and MACCE were also lower after CABG compared to PCI. In the subset of patients studied, low SYNTAX scores (≤22) were present in 29.9% of cases; In this subgroup with low SYNTAX scores, CABG was associated with a significantly lower rate of MI (1.7% vs. 6.9%, p=0.028). In the subgroup with intermediate or high SYNTAX scores (≥23), CABG was associated with lower rates of all-cause death, cardiac death, MI, all-cause revascularization and MACCE. Primary endpoint Heart 2016;0:1–6. doi:10.1136/heartjnl-2016-309720

Impact of the SYNTAX score in patients with diabetes and left-main and/or multivessel coronary disease: a pooled analysis of individual patient level data from the SYNTAX, PRECOMBAT and BEST trials Rafael Cavalcante; Yohei Sotomi; Carlos Collet; Cheol Whan Lee; Jung-Min Ahn; Pannipa Suwannasom; Erhan Tenekecioglu; Yaping Zeng; Yosuke Miyasaki; Yoshinobu Onuma; Pedro A. Lemos; Seung-Jung Park and Patrick W. Serruys In Diabetic patients with MVD the SYNTAX score does impact the difference between CABG and PCI outcomes SYNTAX scores ≤ 32 – PCI is a safe alternative to CABG SYNTAX scores ≥ 33 – CABG is safer than PCI Submitted for publication

Low-intermediate SYNTAX scores (0 – 32) Death, MI or stroke at 5 years Diabetes subgroup (n=1068) according to SYNTAX score Low-intermediate SYNTAX scores (0 – 32) High SYNTAX scores (≥ 33) Cavalcante R, et al. submitted for publication

The advantage of CABG over PCI for multivessel CAD was significantly attenuated if concomitant left main CAD was present. Am J Cardiol 2017;119:225e230

Death from any causes, MI, or stroke In the patients with previous MI and left main or multivessel CAD, compared to PCI with DES, CABG significantly reduces the risk of death from any causes, MI, or stroke. Am J Cardiol. 2016 Jul 1;118(1):17-22.

SYNTAX Score II Variables ANATOMICAL SYNTAX SCORE SYNTAX Score II was developed by applying a Cox proportional hazards model to the results of SYNTAX trial obtaining a combination of clinical and anatomical independent predictors of 4 years all-cause mortality: ANATOMICAL SYNTAX SCORE LM AGE Cr Clearance LVEF Gender PVD COPD Farooq V et al. Lancet 2013; 381: 639–50

The SYNTAX score II has good calibration but only moderate discrimination ability for long-term mortality prediction in this randomized population. This score provides an important tool to help guide the heart team’s decision-making process regarding the selection of the best revascularization strategy for patients with MVD. Whole population MVD PCI MVD CABG n = 1480 n = 438 n = 442 (%) (%) (%) 0.66 1.69 0.74 0.95 Kaplan-Meier Estimated 4 years mortality 0.64 Kaplan-Meier Estimated 4 years mortality 0.97 0.83 0.93 1.12 0.86 0.66 0.56 0.85 0.34 c-index = 0.683 c-index = 0.700 0.0 c-index = 0.661 (%) (%) (%) SYNTAX score II Predicted 4 years mortality SYNTAX score II Predicted 4 years mortality SYNTAX score II Predicted 4 years mortality J Am Coll Cardiol Intv 2016;9:1564–72

Summary CABG, as compared with PCI with drug-eluting stents, significantly reduced the long-term risk of mortality both in diabetic and nondiabetic patients with multivessel CAD. In nondiabetic patients with MVD, the SYNTAX score does impact the difference between CABG and PCI outcomes. In patients with SYNTAX scores ≤ 22, PCI is a safe alternative to CABG, while in patients with SYNTAX scores ≥ 23, CABG is safer than PCI. Also in diabetic patients with MVD, the SYNTAX score does impact the difference between CABG and PCI outcomes. In patients with SYNTAX scores ≤ 32, PCI is a safe alternative to CABG, while in patients with SYNTAX scores ≥ 33, CABG is safer than PCI. In patients with multivessel disease with proximal LAD involvement, CABG is associated with lower rates of the safety composite endpoint of death, MI or stroke as compared with PCI with drug-eluting stents at 5 years of follow-up (number needed to treat=21). The advantage of CABG over PCI for multivessel CAD was significantly attenuated if concomitant left main CAD was present. In the patients with previous MI and left main or multivessel CAD, compared to PCI with DES, CABG significantly reduces the risk of death from any causes, MI, or stroke. The SYNTAX score II has been externally validated and demonstrated its good calibration and moderate discrimination ability for long-term mortality prediction. This score provides an important tool to help guide the heart team’s decision-making process regarding the selection of the best revascularization strategy for patients with MVD.

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SYNTAX Score II EQUIPOISE FOR LONG TERM MORTALITY BETWEEN CABG AND PCI AGE CrCl EF PVD Diabetes COPD 3VD LMS F M EQUIPOISE FOR LONG TERM MORTALITY BETWEEN CABG AND PCI Findings that were validated in the multinational DELTA Registry…

CABG, as compared with PCI with DES, reduced long-term rates of the composite of all-cause death, myocardial infarction, or stroke in patients with left main or multivessel CAD. The advantage of CABG over PCI with DES was particularly pronounced in those with multivessel CAD. J Am Coll Cardiol Intv 2016;9:2481–9