Complex Coronary Cases Supported by: Abbott Vascular Inc Boston Scientific Corp Terumo Vascular Corp Cardiovascular Science Inc Abiomed Inc Chiesi Inc B.Braun Medical Inc

Disclosures Samin K. Sharma, MD, FSCAI, FACC Speaker’s Bureau – Boston Scientific Co, Abbott Vascular Inc, CSI Annapoorna S. Kini, MD, MRCP, FACC Nothing to disclose Sameer Mehta, MD, FACC

CCC Live Case # 124 Present Clinical Presentation Patient Demographics 50 yrs, F Present Clinical Presentation New onset CCS class II angina for last 2 months Clinical Variables Stress echo revealed moderate ischemia in inferior walls Echo: LVEF 60% H/o Hodgkin’s lymphoma and Bladder ca CAD Risk Factors Hypertension Hyperlipidemia NIDDM +F/H Medications Aspirin, Amlodipine, Metoprolol XL, Benazepril, Rosuvastatin, Metformin, Vit D3 Cath: Done on Oct 7th 2019 @OSH revealed 100% CTO of inferior takeoff prox RCA (J-CTO score 4) which fills via collaterals from LAD/LCx, non-obstructive Left system, Syntax score 9 and LVEF 60%. Pt still remain symptomatic despite up titration of MT Plan: PCI of RCA CTO using rotational atherectomy and DES with contralateral injection and antegrade approach and if fails, then retrograde approach

AUC 2017: One-Vessel Disease Patel et al., J Am Coll Cardiol 2017;69:2212

Issues Involving The Case TWILIGHT Trial of Aspirin discontinuation DAPT Trials from TCT 2019: EVOLVE Short DAPT, ONYX ONE, MODEL U-SES

Issues Involving The Case TWILIGHT Trial of Aspirin discontinuation DAPT Trials from TCT 2019: EVOLVE Short DAPT, ONYX ONE, MODEL U-SES

Optimal DAPT duration after DES Implantation 3/6 Months 12 Months 12+ Months Required DAPT Possible DAPT PCI All the RCTs have evaluated abbreviated P2Y12 inhibitor duration: 3-30 months Effectiveness / Safety Uncertain Ischemic Benefit Increased risk for Bleeding!

Aspirin Discontinuation after PCI Background Mandatory 1-month DAPT had been the standard care after BMS. DAPT duration was prolonged after introduction of DES without firm evidence. New generation DES has substantially reduced stent thrombosis. Prolonged DAPT is inevitably associated with increase in bleeding. Bleeding is associated with subsequent mortality risk comparable to MI. Therefore, very short mandatory DAPT duration after DES might be an attractive option, if not associated with increase in ischemic events disproportionate to the reduction in bleeding events. Numerous trials have evaluated short and prolonged DAPT focusing on P2Y12 inhibitor but aspirin was continued. What about aspirin as the culprit for bleeding and no effect on ischemia after PCI?

GLOBAL LEADERS: Trial Profile Primary endpoint: All-cause death and new Q-wave MI @ 2 years Design: Superiority of the experimental arm vs. Reference arm. Serruys PW, ESC 2018

GLOBAL LEADERS: Primary and Pre-specified Secondary Outcomes Experimental Treatment gp (n=7980) Control gp (n=7988) p=0.07 p=0.07 p=0.18 % p=0.77 p=0.14 p=0.90 p=0.98 p=0.39 Death or MI Death MI Stroke Hemorrhagic TVR Def ST BARC 3 or 5 Stroke Vranckx et al., Lancet 2018;392:940

AUGUSTUS Trial: ACS PCI Lopes et al., N Engl J Med 2019;380:1509

SMART-CHOICE Trial: Study Design STOPDAPT-2: Study Flow ASA for 3M ASA for 1M Hahn et al., JAMA 2019;321:2428 Watanabe et al., JAMA 2019;321:2414

SMART-CHOICE: Clinical Outcomes at 1 Year 12/20/2019 SMART-CHOICE: Clinical Outcomes at 1 Year STOPDAPT-2: Clinical Outcomes at 1 Year Death MI ST Stroke Major Bleeding BARC 2-5 p=0.61 p=0.28 p=0.65 p=0.72 p=0.02 p=0.14 % Death MI Def/prob ST Stroke TIMI major/minor Bleeding BARC 3 or 5 p=0.61 p=0.66 p=0.21 p=0.004 p=0.003 p=0.11 % Hahn et al., JAMA 2019;321:2428 Watanabe et al., JAMA 2019;321:2414

TWILIGHT Trial: Hypothesis - In patients undergoing PCI who are at high risk for ischemic or hemorrhagic complications and who have completed a 3-month course of dual antiplatelet therapy with ticagrelor plus aspirin, continued treatment with ticagrelor monotherapy would be superior to ticagrelor plus aspirin with respect to clinically relevant bleeding and would not lead to ischemic harm.

TWILIGHT Trial: Objectives Primary Objective: To determine the impact of SAPT (ticagrelor monotherapy) versus DAPT (ticagrelor plus aspirin) for 12 months in reducing clinically relevant bleeding (BARC 2, 3 or 5) among high-risk patients who have undergone successful PCI. Secondary Objective: To determine the impact of SAPT (ticagrelor monotherapy) versus DAPT (ticagrelor plus aspirin) for 12 months on major ischemic adverse events (all-cause death, non-fatal MI or stroke) among high-risk patients who have undergone successful PCI.

TWILIGHT Trial: Inclusion Criteria Clinical criteria Age ≥65 years Female gender Troponin positive ACS Established vascular disease (previous MI, documented PAD or CAD/PAD revasc) DM treated with medications or insulin CKD (eGFR <60ml/min/1.73m2 or CrCl <60ml/min) Angiographic criteria Multivessel CAD Target lesion requiring total stent length >30mm Thrombotic target lesion Bifurcation lesion(s) requiring ≥2 stents Left main (≥50%) or proximal LAD (≥70%) lesions Calcified target lesion(s) requiring atherectomy

TWILIGHT Trial: Inclusion Criteria Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Randomized Population

TWILIGHT Trial Diagram Enrolled (n=9006) 1:1 Randomized (n=7119) Not Randomized (n=1887) Lost to follow-up (n=106) Adverse events (n=243) Death, MI or stroke (n=111) Any revasc (n=134) BARC 3B or higher bleed (n=52) DAPT non-adherence (n=1148) Consent withdrawal/refusal (n=267) Other reasons (n=123) Ticagrelor + Placebo (n=3555) 15 Month Follow-Up (n=3496; 98.3%) 15 M Vital status (n=3546; 99.7%) Ticagrelor + Aspirin (n=3564) 15 Month F-U (n=3511; 98.5%) (n=3554; 99.7%) 18 withdrew consent 41 lost to follow-up Includes 34 deaths 25 withdrew consent 27 lost to follow-up 1 physician withdrew Includes 48 deaths Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Patient Characteristics Baseline Procedural Details Variable Tica + Placebo (N = 3555) Tica + Aspirin (N = 3564) Radial access 73.1% 72.6% Multivessel CAD 63.9% 61.6% Target vessel LAD 75.1% 74.3% RCA 53.5% 52.5% LCX 46.8% 46.2% Left Main Disease ≥50% 7.9% 8.6% Number of lesions treated 1.5 ± 0.7 Lesion morphology Thrombus 10.4% 10.7% Calcification, moderate/severe 14.0% 13.7% Any bifurcation 12.2% 12.1% Chronic total occlusion 6.2% 6.3% Total stent length 40.1 ± 24.2 39.7 ± 24.3 Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Primary Endpoint (ITT Cohort) BARC 2, 3 or 5 Bleeding Cumulative incidence (%) Ticagrelor + Aspirin (n=3564) Ticagrelor + Placebo (n=3555) 0 3 6 9 12 7.1% Placebo vs Aspirin HR (95%CI): 0.56 (0.45 to 0.68) P <0.001 4.0% ARD = -3.08% (-4.15% to -2.01%) NNT = 33 Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Prespecified Bleeding Endpoints HR [95%CI]: 0.49 [0.33 – 0.74] p = 0.0006 HR [95%CI]: 0.54 [0.37 – 0.80] p = 0.002 HR [95%CI]: 0.53 [0.33 – 0.85] p = 0.008 HR [95%CI]: 0.50 [0.28 – 0.90] p = 0.02 % Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Key Standard Endpoint (PP Cohort) Death, MI or Stroke Cumulative incidence (%) Ticagrelor + Aspirin (n=3564) Ticagrelor + Placebo (n=3555) 0 3 6 9 12 Placebo vs Aspirin HR (95%CI): 0.99 (0.78 to 1.25) Pnon-inferiority <0.001 3.9% 3.9% ARD = -0.06% (-0.97% to 0.84%) Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Prespecified Ischemic Endpoints HR [95%CI]: 0.97 [0.76 - 1.24] p = 0.80 HR [95%CI]: 1.00 [0.75 - 1.33] p = 0.99 HR [95%CI]: 0.75 [0.48 - 1.18] p = 0.21 HR [95%CI]: 0.74 [0.37 – 1.47] p = 0.38 % HR [95%CI]: 1.80 [0.83 - 3.90] p = 0.13 Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Subgroup Analysis for Primary Endpoint Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

TWILIGHT Trial: Landmark Analysis Key Secondary Endpoint Primary Endpoint BARC 2, 3 or 5 Bleeding Key Secondary Endpoint Death, MI or Stroke Mehran et al., N Engl J Med 2019 Sept 26 [Epub ahead of print]

Ticagrelor With AspIrin or ALone In HiGH-Risk Patients After Coronary InTervention: Thrombogenicity Substudy

TWILIGHT Trial: Study Schema Baber U, TCT 2019

TWILIGHT Trial: Badimon Perfusion Chamber Baber U, TCT 2019

TWILIGHT Trial: Ex-Vivo Thrombus Area by Treatment Group 1000 3000 5000 7000 Thrombus Area at Follow-Up (µm2) Thrombus Area at Randomization (µm2) Ticagrelor Plus Aspirin Ticagrelor Plus Placebo Mean Difference (95% CI) in Thrombus Area Between Groups: 218.2 µm2 (-575.9 to 139.9); p=0.22 Baber U, TCT 2019

Platelet Aggregation (U) TWILIGHT Trial: Post-Randomization Platelet Reactivity by Treatment Group p=0.81 p=0.03 Platelet Aggregation (U) p=0.02 p=0.47 Baber U, TCT 2019

YES

Issues Involving The Case TWILIGHT Trial of Aspirin discontinuation DAPT Trials from TCT 2019: EVOLVE Short DAPT, ONYX ONE, MODEL U-SES

EVOLVE Short DAPT: A Single Arm Study of 3-Month DAPT in Patients at High Bleeding Risk Treated with a Bioabsorbable Polymer-Based Everolimus-Eluting Stent

EVOLVE Short DAPT: Study Design Prospective, multicenter, single-arm study powered to define safety of 3-month DAPT in high bleeding risk (HBR) patients treated with SYNERGY Aspirin Only (patients eligible† for discontinuation of P2Y12 inhibitor) 3 15 DAPT (Aspirin optional if on chronic anticoagulation) PCI Clinical follow-up Final follow-up Time in months after SYNERGY stent implantation Analysis period Co-Primary endpoints: Death/MI and ARC definite/probable ST between 3-15 months Secondary endpoint: BARC 2/3/5 bleeding between 3-15 months (patients not on chronic anticoagulation) †Subjects free from stroke, MI, revascularization and ST between 0-3 months eligible to discontinue; Mauri et al. Am Heart J 2018;195:115 Kirtane A, TCT 2019

EVOLVE Short DAPT: Study Population Key Inclusion Criteria: Patient considered at high risk for bleeding, if met one or more of the following criteria at the time of enrollment: ≥75 years of age and, in the opinion of the investigator, risk of bleeding associated with >3 months of DAPT outweighs the benefit History of major bleeding (severe/life threating/moderate GUSTO classification) within 12 month of index procedure History of stroke (ischemic or hemorrhagic) Renal insufficiency (creatinine ≥2.0 mg/dl) or failure (dialysis dependent) Platelet count ≤100,000/μL Need for chronic or lifelong anticoagulation therapy* Key Exclusion Criteria: Planned treatment of >3 lesions or lesions in >2 major epicardial vessels In-stent restenosis or left main disease Complex bifurcation, ostial lesions, or saphenous vein graft lesions TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing Non-ST-elevation MI (NSTEMI) or STEMI *Due to higher than expected enrollment of patients on anticoagulation therapy, a cap (30%) was placed on patients taking (or planning to take) chronic or lifelong anticoagulation within 15 months following index procedure (allowing equivalent comparison between the test and control groups); Mauri et al. AHJ 2018 Kirtane A, TCT 2019

EVOLVE Short DAPT: Patient Disposition Not eligible to discontinue P2Y12 inhibitor at 3 months: N=425 (22.3%) Not event-free (52); DAPT non-compliant (34); DAPT interruption ≥14 days (31); other (24); investigator decision (183); subject decision (152)‡ Eligible to discontinue P2Y12 inhibitor at 3 months†: N=1487 (77.7%) Analysis population: Death/MI and ST, n=1487; BARC 2,3,5 bleeding, n=1032 (excluded 455 patients on anticoagulation) Clinical follow-up at 3 months: N=1912 (95.2%) 2009 patients implanted with at least 1 SYNERGY stent at 110 global sites Withdrawn*: n=44 Death: n=37 Missed visit: n=16 Withdrawn*: n=40 Death: n=19 15-month follow-up: N=1385 (93.1%) 15-month follow-up: N=366 (86.1%) Withdrawn*: n=36 Death: n=66 *withdrawn due to adverse event, lost to follow-up, investigator discretion, or other reasons; †patients free from stroke, MI, revascularization and ST between 0-3 months eligible to discontinue; ‡patients may have had multiple reasons for not being eligible Kirtane A, TCT 2019

EVOLVE Short DAPT: Analysis Population Age Gender BMI 34% 66% BMI: 28.7± 5.7 Height: 170.0 ± 10.9 cm 75.7 ± 8.5 years Weight: 83.5 ± 20.6 kg HBR patients with SYNERGY stent implanted N=1487 Age ≥ 75 yrs, and, risk of major bleeding associated with >3m DAPT outweighs the benefit 67.5% (1003) Need for chronic or lifelong anticoagulation therapy 30.6% (455) History of major bleeding (GUSTO severe/life threating/moderate) within 12m of index procedure 2.7% (40) History of stroke (ischemic or hemorrhagic) 13.4% (200) Renal insufficiency (creatinine ≥ 2.0 mg/dl) or failure (dialysis dependent) 9.1% (136) Platelet count ≤ 100,000/μL 2.0% (29) Subjects met more than one HBR criteria: 22.9% # of HBR criteria met/subject: 1.3 ± 0.5 Kirtane A, TCT 2019

EVOLVE Short DAPT: Key Lesion Characteristics – Analysis Population Lesion Characteristics* (1487 patients, 1865 lesions) Lesion length (mm), Mean ± SD 17.2 ± 9.5 <10 mm 16.0% 10 – 28 mm 72.7% >28 mm 11.3% Target lesion location: LAD 45.6% LCx 24.2% RCA 30.1% RVD (mm), Mean ± SD 3.0 ± 0.5 2.25 – <2.5 mm 8.9% 2.5 – <2.75 mm 23.3% ≥2.75 mm 66.4% Diameter Stenosis (%), Mean ± SD 82.6 ± 9.8 TIMI flow 3 88.4% Modified AHA/ACC B2/C 47.3% Calcification, Moderate/Severe 29.1% Tortuosity, Moderate/Severe 16.9% Kirtane A, TCT 2019

EVOLVE Short DAPT: Clinical Outcomes Analysis Population (N=1457) Between 3-15 Months Analysis Population (N=1457) Type 2 4.6% (67) Type 3 2.7% (30) Type 5 0.2% (3) Binary rates; denominator includes patients with sufficient f/u or having a CEC event; *Non-hierarchical Kirtane A, TCT 2019

EVOLVE Short DAPT: Co-Primary Endpoint Adjusted Death/MI Between 3-15 Months with 3-Month DAPT Compared to Historical Control N=1493 N=1454 Difference [97.5% UCB] p=0.0016 Non-inferiority margin: 2.52% 1.63% 1-sided UCB* Patients with respective event or sufficient follow-up included in the denominator Kirtane A, TCT 2019

EVOLVE Short DAPT: Secondary Endpoint Adjusted BARC 2, 3, 5 Bleeding Between 3-15 Months 12-Month DAPT (N=947) 3-Month DAPT (N=974) Difference [95% CI] Superiority Test P value BARC 2,3,5 Bleeding 4.17% 6.26% 2.10% [-0.10%, 4.29%] 0.98 Type 2 2.12% 3.64% 1.52% [-0.16%, 3.19%] - Type 3 2.32% 2.67% 0.35% [-1.17%, 1.87%] Type 5 0.00% 0.27% [-0.05%, 0.60%] Kirtane A, TCT 2019

Conclusions EVOLVE Short DAPT was designed to evaluate the safety of DAPT discontinuation at 3 months in HBR subjects treated with SYNERGY Bleeding risk was significant, and key subgroups (age≥75 with risk/benefit favoring shorter DAPT, need for anticoagulation) were well- represented The study met both co-primary endpoints despite incomplete event adjudication in the control group, with favorable rates of ischemic outcomes from 3-15 months after discontinuation of P2Y12 inhibitor Death/MI (adjusted): 5.6%; Definite/probable ST: 0.3%; MI: 1.9% These data support the use of SYNERGY with a 3-month duration of DAPT in HBR patients

Onyx ONE – A Randomized Trial of a Durable-Polymer Drug-Eluting Stent vs. a Polymer-Free Drug-Coated Stent in Patients at High Risk of Bleeding Treated With 1-Month DAPT

Onyx ONE: Objective To compare the safety and efficacy of a durable polymer-based zotarolimus-eluting stent (Resolute Onyx) with a polymer-free biolimus A9-drug coated stent (BioFreedom) among HBR patients undergoing PCI with planned 1-month DAPT Windecker S, TCT 2019

Onyx ONE: Study Devices Resolute Onyx™ DES BioFreedom™ DCS Metallic stent material CoCr with platinum iridium core 316L Stainless steel Antiproliferative drug Zotarolimus Biolimus A9™ Stent surface characteristic BioLinx™, biocompatible durable polymer Polymer-free, selectively micro-structured abluminal surface Strut thickness (μm) 81 – 91 μm 112 μm Available stent diameters 2.0 – 5.0 mm 2.25 – 4.0 mm Windecker S, TCT 2019

Onyx ONE: Global Study Design Prospective, Multicenter, Single-blind Randomized Trial 1:1 randomization 84 global sites Enrollment Nov 2017 – Sep 2018 Clinical Follow-up Resolute Onyx™ ZES with 1 Month DAPT (N=1000) BioFreedom™ DCS 2mo 2yr 1yr 1mo 6mo Primary safety endpoint: Cardiac death, MI or stent thrombosis (def/prob) at 1 year 2° Efficacy endpoint (powered): Target Lesion Failure (TLF; cardiac death, TV-MI or cd-TLR) at 1 year Other secondary endpoints: Lesion, device and procedure success rates, BARC bleeding, individual components of primary endpoints High Bleeding Risk patients undergoing PCI (no lesion, vessel limitations) Kedhi et al., Am Heart J 2019;214:134

Onyx ONE: HBR Inclusion Criteria (One or More) Elderly age ≥75 years Thrombocytopenia (<100,000/mm3) OAC planned after PCI Cancer diagnosed or treated within 3 yrs Renal failure (CrCl <40 ml/min) Stroke within 1 year or any prior ICH Planned surgery <1 year Severe chronic liver disease Anemia (Hgb <11 g/dl) Long-term NSAID or steroid use Hospitalization for bleeding within 1 year Expected DAPT non-compliance Kedhi et al., Am Heart J 2019;214:134

Onyx ONE: Antithrombotic Therapy After PCI, 1-month DAPT was prescribed, including: Daily dose of aspirin (75-100 mg) AND P2Y12 inhibitor (clopidogrel preferred, others allowed) Patients receiving OAC could receive single or dual antiplatelet therapy during this 1st month after PCI After 1-month DAPT, single antiplatelet therapy was prescribed (at physician discretion): Either aspirin OR P2Y12 inhibitor PCI 1M Windecker S, TCT 2019

1-Year Follow-up Analysis Onyx ONE: Patient Flow BioFreedom DCS N=993 ITT Population Resolute Onyx ZES N=1003 12 withdrawal 3 visit not done 19 withdrawal 5 visit not done 1-Year Follow-up Analysis n=988 (98.5%) n=969 (97.6%) Randomized N=1996 979 Implanted ZES only 2 Cross-over to implanted DCS only 7 Implanted non-study stent 15 No procedure or stent implanted 932 Implanted DCS only 40 Cross-over to implanted ZES only 7 Implanted DCS, ZES and/or non-study stent 14 No procedure or stent implanted Windecker S, TCT 2019

17.1% 16.9% Onyx ONE: Primary Safety Endpoint Cardiac Death, MI, ST Resolute Onyx (N=1003) 17.1% BioFreedom (N=993) 16.9% Difference: 0.2% Upper 1-sided 95% CI: 3.0% P-value non-inferiority 0.011 Non-inferiority margin = 4.1% -2% -1% 1% 2% 3% 4% 5% Non-Inferiority Endpoint Met Windecker S, TCT 2019

Onyx ONE: Primary Safety Endpoint And Components Windecker S, TCT 2019

Onyx ONE: One-Month Landmark Analyses (Time of DAPT Discontinuation) Windecker S, TCT 2019

Onyx ONE: Powered Secondary Effectiveness Endpoint – TLF at 1 Year Resolute Onyx ZES (n=988) BioFreedom DCS (n=969) 1-Year Event Rates (%) P = 0.95 PNI = 0.007 P = 0.17 P = 0.43 Windecker S, TCT 2019

Onyx ONE: BARC Bleeding Rates at 1 Year 1-Year Bleeding Rates (%) Resolute Onyx ZES (n=988) BioFreedom DCS (n=969) P = 0.43 P = 0.40 P = 0.67 1-Year Bleeding Rates (%) Windecker S, TCT 2019

Onyx ONE: Summary ONYX ONE is a contemporary trial: First trial comparing DES versus DCS Investigating 1-month DAPT Very complex HBR patient and lesion population Among HBR patients treated with 1-month DAPT after PCI, Resolute Onyx was as safe and effective as BioFreedom Resolute Onyx had improved angiographic outcomes and greater device success post-PCI

3-Month Discontinuation of Dual Antiplatelet Therapy After Bioresorbable Polymer Sirolimus-Eluting Stent Implantation: MODEL U-SES study

MODEL U-SES Study Design Prospective multicenter single-arm registry, Investigators initiated study with 65 sites from Japan Primary endpoint Ischemic and bleeding event at 12 months Patients treated with U-SES and considered appropriate to 3-month DAPT after implantation. (n=1,500) Discontinuation of Aspirin or P2Y12 inhibitor at 3 months Enrollment after IC Patient level propensity adjusted Historical control CENTURY II (Longer DAPT) Clinicaltrials.gov NCT02837003 Primary Endpoint: A composite of all cause death, myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), BARC type 3 or 5 bleeding at 1 year Kozuma K, TCT 2019

MODEL U-SES Study: Patient Flow Enrolled (n=1,695) Enrollment from 65 Japanese centers between October 2016 and March 2018 3 = Withdraw consent, 6 = Exclusion criteria 3 = Found to be double registration 4 = DES implantation other than BP-SES 3-month Clinical Follow-up (n=1,686; 99.5%) 1-Year Clinical Follow-up (n=1,616; 95.3%) Patients treated with BP-SES (n=1,711) 26 patients continued DAPT for 12 months 22 = lost to follow-up, 25 death Aspirin continuation (n=846) P2Y12 Inhibitors (n=674) Kozuma K, TCT 2019

MODEL U-SES Study: Baseline Patient Characteristics (in MODEL U-SES) MODEL U-SES (n=1,695) Age, years 69.7 ± 10.6 Age 75 years 36.2% Male gender 76.8% Body mass Index, kg/m2 24.3 ± 3.5 Diabetes 39.3% Hypertension 79.9% Dyslipidemia 80.8% Current smoker 21.7% Severe CKD 13.0% Hemodialysis 5.3% Prior stroke 10.4% Heart failure 27.2% Atrial fibrillation 8.2% Peripheral vascular disease 6.7% Clinical diagnosis 　Acute myocardial infarction 15.3% STEMI 11.7% NSTEMI 3.7% 　Unstable angina 13.1% 　Stable coronary artery disease 46.6% Silent ischemia 22.2% Old myocardial infarction 5.7% Previous GI bleeding 2.3% Previous peptic ulceration 2.2% Previous carotid artery disease 3.8% Malignancy 8.8% Anemia, Hb <11.0 g/dL 9.8% Prior PCI 38.9% Prior CABG 2.8% Family history of CV disease 15.5% Kozuma K, TCT 2019

MODEL U-SES Study: All cause death, MI, Stroke, ST, and Bleeding (BARC 3 or 5) at 1 Year - Primary Endpoint - 4.4% Kozuma K, TCT 2019

MODEL U-SES Study: Primary Endpoint at 1 Year All cause death, MI, Stroke, ST, and Bleeding (BARC 3 or 5) Propensity score subclassification adjustment analysis MODEL U-SES (N= 1,616) CENTURY II BP-SES (N= 542) Difference One Sided 95% Upper Confidence Bound Delta P non-inferiority 4.3% (69 /1,616 ) 5.7% (31 /542 ) -3.17% -0.86% 3.50% <.0001 Kozuma K, TCT 2019

MODEL U-SES Study: Landmark Analysis at 90 Days All cause death, MI, Stroke, ST, and Bleeding (BARC 3 or 5) With Propensity Score Adjustment Kozuma K, TCT 2019

MODEL U-SES Study: Landmark Analysis at 90 Days With Propensity Score Adjustment Cardiovascular Death, MI, Stroke, and ST Bleeding (BARC 3 or 5) Kozuma K, TCT 2019

MODEL U-SES Study: 1 Year Clinical Outcomes Primary Endpoint: All cause death, MI, Stroke, ST, and Bleeding (BARC 3 or 5) % Kozuma K, TCT 2019

MODEL U-SES Study: Landmark Analysis at 90 Days All cause death, MI, Stroke, ST, and Bleeding (BARC 3 or 5) Kozuma K, TCT 2019

MODEL U-SES Study: Landmark Analysis at 90 Days With IPTW Analysis Cardiovascular Death, MI, Stroke, and ST Bleeding (BARC 3 or 5) Kozuma K, TCT 2019

MODEL-U SES: Conclusions This study demonstrated that 3-month DAPT was non-inferiority to adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. P2Y12 inhibitor monotherapy was almost equivalent to Aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.

Take Home Message: TWILIGHT Trial and DAPT Trials from TCT 2019 TWILIGHT trial is a landmark study showing that even in high clinical angiographic risk cases, stopping aspirin after 3M post PCI and continuing ticagrelor for additional 12 months, is associated with significantly lower bleeding and no difference in the ischemic endpoints including ST. It was true for both ACS and stable CAD pts. This trial is yet another trial revealing that aspirin discontinuation after 1-3M post PCI is safe and appropriate after current DES PCI. In pts with high bleeding risk a strategy of single antiplatelet therapy (SAPT) of P2Y12 or aspirin is safe after 1-3M of DES implantation. Now numerous trials have shown that DAPT abbreviation to 1-3M post current DES is safe with no increase in ischemic endpoints or ST. Therefore, guidelines need to incorporate these observations.

Question # 1 The correct answer is D TWILIGHT trial evaluated Ticagrelor therapy in all following clinical scenario except; Diabetes Stable complex CAD Unstable complex CAD STEMI E. Bifurcation CAD The correct answer is D

Question # 2 The correct answer is C Following are the correct conclusion of the TWILIGHT trial except; Aspirin discontinuation after 3M resulted in lower bleeding Aspirin discontinuation after 3M was associated with similar ischemic endpoints Aspirin discontinuation after 3M showed trend towards higher ST Ticagrelor alone was effective in both stable and ACS CAD Ticagrelor alone was effective irrespective of lesion morphology The correct answer is C

Question # 3 The correct answer is B Following are the trials evaluating DAPT duration except: A. EVOLVE short DAPT Trial B. AUGUSTUS Trial C. MODEL U-SES Trial D. ONYX One Trial E. SMART Choice Trial The correct answer is B