1. 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

2. 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

3. 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 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

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

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

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

7. 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!

8. 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?

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

10. 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

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

12. 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

13. 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

15. 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.

16. 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.

17. 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

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

19. TWILIGHT Trial: Randomized Population

20. 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]

21. 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]

22. TWILIGHT Trial: Primary Endpoint (ITT Cohort)
BARC 2, 3 or 5 Bleeding
Cumulative incidence (%)
Ticagrelor + Aspirin (n=3564)
Ticagrelor + Placebo (n=3555)
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]

23. TWILIGHT Trial: Prespecified Bleeding Endpoints
HR [95%CI]:
0.49 [0.33 – 0.74]
p =
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]

24. TWILIGHT Trial: Key Standard Endpoint (PP Cohort)
Death, MI or Stroke
Cumulative incidence (%)
Ticagrelor + Aspirin (n=3564)
Ticagrelor + Placebo (n=3555)
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]

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

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

27. 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]

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

29. TWILIGHT Trial: Study Schema
Baber U, TCT 2019

30. TWILIGHT Trial: Badimon Perfusion Chamber
Baber U, TCT 2019

31. 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 ( to 139.9); p=0.22
Baber U, TCT 2019

32. 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

34. YES

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

36. 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

37. 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

38. 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

39. 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

40. EVOLVE Short DAPT: Analysis Population
Age
Gender
BMI
34%
66%
BMI:
28.7± 5.7
Height:
170.0 ± 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

41. 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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. Onyx ONE: Antithrombotic Therapy
After PCI, 1-month DAPT was prescribed, including:
Daily dose of aspirin ( 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

52. 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

53. 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

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

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

56. 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

57. 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

58. 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

59. 3-Month Discontinuation of Dual Antiplatelet Therapy After Bioresorbable Polymer Sirolimus-Eluting Stent Implantation: MODEL U-SES study

60. 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
NCT
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

61. MODEL U-SES Study: Patient Flow
Enrolled
(n=1,695)
Enrollment from 65 Japanese centers
between October 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

62. 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

63. 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

64. 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

65. 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

66. 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

67. 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

68. 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

69. 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

70. 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.

71. 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.

72. 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

73. 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

74. 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