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

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

3. CCC Live Case # 121 Present Clinical Presentation Patient Demographics
Cresendo CCS class II angina
for last 2 months despite MMT
even after last PCI
Patient Demographics
82 yrs, F
Stable angina
s/p CABG and multiple PCIs
Clinical Variables
Stress MPI revealed ischemia
in anterior, apical & inferior walls
Echo: LVEF 60%
CABG x3 in 1998
s/p last DES PCI of dLAD via LIMA 5/19
CAD Risk Factors
Hypertension
Hyperlipidemia
NIDDM
Medications
Aspirin, Clopidogrel, Carvedilol, ISMN, Rosuvastatin, Telmisartan, Metformin, Sitagliptin, Hydralazine, Synthroid, Amlodipine, Omeprazole
Cath: 3 V CAD, Occluded mid-distal RCA, prox LAD & LCX-OM1, 80% D1, 90%
native dLAD with patent LIMA, patent SVG to OM1 & TO SVG to RCA
Plan: PCI of multiple 20 yrs old CTO lesions of native m-dRCA guided by
contralateral injection

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

5. Issues Involving The Case
Recent publications in CTO Interventions
Aspirin discontinuation after PCI

6. Issues Involving The Case
Recent publications in CTO Interventions
Aspirin discontinuation after PCI

7. J-CTO Score Sheet
Morino et al., J Am Coll Cardiol Intv 2011;4:213

9. Multivariable Logistic Regression Analysis for Failure of PCI by
the EuroCTO CASTLE Model and the Assignment of Risk Scores
to the Risk Factors on the Imputed Derivation Set
Szijgyarto et al., J Am Coll Cardiol Intv 2019;12:335

10. EuroCTO (CASTLE) Scoring System
Comprised of 2 Clinical Factors and 4 Angiographic Factors:
CABG, prior
Age, ≥70 years
Stump anatomy, blunt or invisible proximal cap
Tortuosity degree, severe
Length of occlusion, ≥ 20 mm
Extent of calcification, severe
With 1 point for each factor resulting in score of 0 to 6
J-CTO score: Previously failed attempt, blunt stump,
bending, severe calcification and occlusion length >20mm

11. EuroCTO (CASTLE) Score:
Risk Scores and Predicted Probabilities of Failure of PCI for Patients in the EuroCTO Registry Derivation Dataset from 2008 to 2014
Distribution of total risk scores of
14,882 patients with CTO
Red line shows predicted procedural failures
Szijgyarto et al., J Am Coll Cardiol Intv 2019;12:335

12. Model Calibration in EuroCTO Registry Derivation Dataset from 2008 to 2014 (n=14,882)
Comparison of the observed and predicted probabilities of failure of PCI across the 4 risk groups: tortuosity, calcification, stump , length of CTO
Szijgyarto et al., J Am Coll Cardiol Intv 2019;12:335

13. Risk Scores and Calibration of the CASTLE Model
in the EuroCTO Registry Validation Dataset from
2015 and 2016
Comparison of the observed and predicted probabilities of failure of PCI computed by the EuroCTO CASTLE score
Distribution of the risk scores of 5,745 pts with CTO
Szijgyarto et al., J Am Coll Cardiol Intv 2019;12:335

16. Observed Rates of Technical Success of CTO PCI
CTO PCI across J-CTO Score Strata
CTO PCI across EuroCTO
(CASTLE) Score Strata
Distribution of EuroCTO (CASTLE) Score Strata
Distribution of J-CTO Score Strata
Kalogeropoulos et al., EuroIntervention 2019 Jul 2 Epub ahead of print

17. Success Predictors for the J-CTO and EuroCTO (CASTLE) Scores
Whole Study Cohort
Complex Cases
Kalogeropoulos et al., EuroIntervention 2019 Jul 2 Epub ahead of print

20. Flow Diagram of the Study Selection Process
143 citations identified through database and manual search (after elimination of duplicates)
13 citations fully reviewed
Nine studies were included in the meta-analysis
(all observational studies)
Excluded:
69: Irrelevant
35: Reviews, description of techniques, case reports
23: Non-human
3: Abstracts
4: single arm studies
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

21. Baseline Characteristics of the Included Studies
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

22. Baseline Characteristics of the Study Patients
and Lesions
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

23. Technical Success with Radial vs Femoral Approach in CTO PCI (n=10,590)%
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

24. In-Hospital Outcomes of Radial vs Femoral Approach in CTO PCI (n=10,590)%
p=0.13
p<0.001
p=0.07
p=0.63
p=0.80
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

25. Pooled Analysis of In-Hospital Events with
Radial vs. Femoral Approach in CTO PCI
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

26. Pooled Analysis of the Technical Success, Access-Site Complications, Major Bleeding, Contrast Volume and Fluoroscopy Time with Pure Radial vs. Femoral Approach in CTO PCI
Megaly et al., Circ Cardiovasc Interv 2019;12:e007778

30. OPEN-CTO: Operator-Reported Approach Used
and the Actual Antegrade/Retrograde Strategy That Caused Perforation
Hirai et al., J Am Coll Cardiol Intv 2019 Jun 19 Epub ahead of print

31. Summary of Size and Location of Clinical and Nonclinical Perforations from the OPEN-CTO Registry
Hirai et al., J Am Coll Cardiol Intv 2019 Jun 19 Epub ahead of print

33. Issues Involving The Case
Recent publications in CTO Interventions
Aspirin discontinuation after PCI

34. 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!

35. Aspirin Discontinuation after PCI
Background
Mandatory 1-month DAPT had been the standard care after BMS implantation.
DAPT duration was prolonged after introduction of DES without firm scientific 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 at least comparable to that of 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.

36. Ongoing Studies Examining Abbreviated Duration of DAPT-SAPT
ASA
Ticagrelor 24M
ASA
Ticagrelor 15M

38. 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

39. GLOBAL LEADERS Adherence to Treatment Strategies
Primary and Secondary Outcomes at 12 Months (Intention to Treat)
Serruys PW, ESC 2018

40. GLOBAL LEADERS: KM Estimate of Mortality and Safety Outcome at 2 Years
Vranckx et al., Lancet 2018;392:940

41. GLOBAL LEADERS: Primary and Prespecified 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

42. My interpretation is more+:
Global leaders has opened the door for future trials of eliminating aspirin after short time post PCI to decrease bleeding without affecting ST

43. TWILIGHT Study: Evaluation of Ticagrelor Monotherapy in Patients Who Have Undergone
High Risk PCI with DES
Open-label ticagrelor; double-blinded ASA or placebo
Ticagrelor 90 mg bid + Placebo
Standard of care therapy at the discretion of treating physician
Observation period
Open-label after index PCI
Ticagrelor 90 mg bid + ASA 81–100 mg od
Randomization if event-free (N=8200)
Enrollment
(N=9000)
High-risk patients aged ≥18 years undergoing PCI with at least 1 DES placement
15 months
18 months
3 months
Primary endpoint: clinically relevant (BARC class 2, 3, or 5) bleeding during months 3–15
Key secondary endpoint: composite of all-cause death, non-fatal MI, ischaemic stroke

44. Trial completed enrollment and F/U. Will be presented in TCT Sept 2019
TWILIGHT Study: Enrollment of High-Risk Patients Undergoing PCI With At Least One DES Placement
Inclusion Data
Age ≥18 years of age
Undergoing PCI with at least 1 DES placement
Must meet ≥1 criteria from both clinical and angiographic specifications:
Clinical:
Angiographic:
≥65 years of age
Female
Troponin positive ACS
Established vascular disease (previous MI, documented PAD or CAD/PAD revasc)
DM treated with medications
CKD (eGFR <60 mL/min/1,73 m2 or CrCl <60 mL/min
Multivessel CAD
Target lesion stent length >30 mm
Thrombotic target lesion
Bifurcation lesions with Medina X, 1, 1 classification requiring ≥2 stents
Left main ≥50% or proximal LAD ≥70% lesion
Calcified target lesion requiring atherectomy
Trial completed enrollment and F/U.
Will be presented in TCT Sept 2019

45. 10/9/2019

46. SMART-CHOICE Trial: Study Design
10/9/2019
A Perspective, Multicenter, Randomized, Open-Label,
Non-Inferiority Trial
77% Clopidogrel
23% Prasugrel/
Ticagrelor
Hahn et al., Am Heart J 2018;199:7

47. SMART-CHOICE Trial: Study Design
10/9/2019
Hahn et al., JAMA 2019;321:2428

48. SMART-CHOICE Trial: Adherence of Antiplatelet
10/9/2019
Hahn et al., JAMA 2019;321:2428

49. SMART-CHOICE Trial: Primary Endpoint
(MACCE)
10/9/2019
Hahn et al., JAMA 2019;321:2428

50. SMART-CHOICE Trial: Time-to-Event Curves for
MACCE and Landmark Analysis at 3 Months
10/9/2019
Hahn et al., JAMA 2019;321:2428

51. SMART-CHOICE Trial: Time-to-Event Curves for Bleeding and Landmark Analysis at 3 Months
10/9/2019
Hahn et al., JAMA 2019;321:2428

52. SMART-CHOICE Trial: Clinical Outcomes
at 12 Months
10/9/2019
Hahn et al., JAMA 2019;321:2428

53. 10/9/2019

55. STOPDAPT-2: Prospective multicenter open-label randomized trial comparing 1-month versus 12-month DAPT after CoCr-EES implantation with limited exclusion criteria.
Watanabe et al., JAMA 2019;321:2414

56. STOPDAPT-2 Study Flow All EES 60% Clopidogrel 40% Prasugrel
Watanabe et al., JAMA 2019;321:2414

57. STOPDAPT-2: Baseline Clinical Characteristics
1-month DAPT (N=1500)
12-month DAPT (N=1509)
Age, years
68.1±10.9
69.1±10.4
Men
79%
77%
ACS
38%
39%
STEMI
19%
18%
Stable CAD
62%
61%
Diabetes
Severe CKD IV 6%
Prior MI
14%
13%
Prior PCI
34%
35%
CREDO-Kyoto thrombotic risk score
High; Intermediate; Low
8%; 21%; 71%
8%; 24%; 68%
CREDO-Kyoto bleeding risk score
7%; 27%; 66%

58. STOPDAPT-2: Procedural Characteristics and Medications
1-month DAPT (N=1500)
12-month DAPT (N=1509)
Transradial approach
82%
84%
N for target lesions
1.12±0.35
1.14±0.39
Minimal stent diameter, mm
2.98±0.49
2.96±0.48
Total stent length, mm
30.3±16.7
30.5±16.8
SYNTAX Score
8 (5-14)
9 (6-15)
Target of LMCA 3%
CTO 4%
IVUS or CTO
97%
98%
ASA
99.8%
100%
Clopidogrel
60%
63%
Prasugrel (3.75 mg/day)
40%
37%
Statin
88%
87%
PPI
79%
Watanabe et al., JAMA 2019;321:2414

59. STOPDAPT-2: Persistent DAPT Discontinuation
Watanabe et al., JAMA 2019;321:2414

60. STOPDAPT-2:Primary Endpoint: Net Clinical Benefit
CV Death/MI/ST/Stroke/TIMI Major/Minor Bleeding
Watanabe et al., JAMA 2019;321:2414

61. STOPDAPT-2:Major Secondary Ischemic Endpoint CV Death/MI/ST/Stroke
Watanabe et al., JAMA 2019;321:2414

62. STOPDAPT-2: Major Secondary Ischemic Endpoint
TIMI Major/Minor Bleeding
Watanabe et al., JAMA 2019;321:2414

63. STOPDAPT-2: Clinical Outcomes at 1 Year
10/9/2019
STOPDAPT-2: Clinical Outcomes at 1 Year
P values for superiority
p=0.003
p=0.61
p=0.004
p=0.11
p=0.66 %
p=0.21
Death MI
Def/prob ST
Stroke
TIMI
major/minor
Bleeding
BARC 3 or 5
Bleeding
Watanabe et al., JAMA 2019;321:2414

68. Take Home Message: Recent data on CTO PCI and Aspirin discontinuation post-PCI
Novel new score from Euro CTO club (CASTLE) is yet another simple risk score for prediction of CTO success. It has better discriminatory power then J-CTO score in more complex cases. Data support the use of radial access versus femoral access in less complex CTO with resultant similar success but lower vascular & bleeding complications.
Novel approach of limiting aspirin duration as part of DAPT strategy post PCI has taken the momentum now with numerous RCT limiting aspirin duration to 1-3 mths and resulting in similar (or better) efficacy and lower bleeding. Final answer to this question will be revealed by the results of TWILIGHT trial where aspirin was d/c after 3 mths with continued Ticagrelor monotherapy vs routine DAPT.

69. Question # 1 The correct answer is D
Following are the features which makes the EuroCTO CASTLE score except;
Prior CABG
Age
Lesion calcification
Prior failed attempt
E. Lesion length
The correct answer is D

70. Question # 2 The correct answer is C
Following statements are true for the radial access from the meta-analysis of radial vs femoral CTO intervention except;
Both approaches have similar technical success
Radial approach has lower vascular complication
Radial approach is more commonly used in complex cases
Radial approach has similar mortality
Radial approach has similar procedural complications
The correct answer is C

71. Question # 3 The correct answer is B
Following are the RCTs of aspirin discontinuation after PCI except?
A. GLOBAL LEADERS
B. DAPT
C. STOP DAPT-2
D. SMART CHOICE
E. TWILIGHT
The correct answer is B

72. Question # 4 The correct answer is C
Following statements are true from the aspirin discontinuation trials after PCI except;
Aspirin d/c group has lower bleeding
Aspirin d/c group has similar or better efficacy
Aspirin d/c group has higher ST
Aspirin d/c group similar CVA rates
Aspirin d/c group has similar primary endpoints in first 1-3M
The correct answer is C

73. Question # 5 The correct answer is B
Following statements are true for the TWILGHT trial of aspirin discontinuation post PCI except?
A. Pt were randomized after 3 M of DAPT
B. Pt received Clopidogrel in the experimental arm
C. Primary endpoint of the trial is incidence of bleeding
D. Trial duration is 15 months post PCI
E. Ticagrelor was used in many stable PCI pts
The correct answer is B