1. Complex Coronary Cases
Supported by:
Abbott Vascular Inc
Boston Scientific Corp
Terumo Vascular Corp
Vascular Solutions Inc
Cardiovascular Science Inc
AstraZeneca Pharmaceuticals
The Medicines Company
Trireme Medical

2. Disclosures
Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, ABIOMED, CSI, Trireme Medical Annapoorna S. Kini, MBBS, FACC Nothing to disclose Sameer Mehta, MBBS, FACC Consulting Fees – The Medicines Company

3. October 20th 2015 Case #76: SS, 77 yrs F
Presentation:
Patient with moderate COPD and non-obstructive CAD in 2012, presented with cresendo angina (CCS class III). A stress MPI revealed mild infero-apical ischemia. Pt is on the tolerable MMT and still symptomatic. A cardiac cath on Oct 19th 2105 revealed 1 V +LM CAD, LVEF 60% and SYNTAX score 24. Heart team discussion took place and PCI is recommended.
Prior History:
Hypertension, Hyperlipidemia, COPD with FEV1 62%
Medications: All once daily dosage
ASA 81mg, Cardizem 180mg, ISMN 60mg, Simvastatin 40mg, Albuterol, Tizanidine 4mg (BB contraindicated due to COPD) 3

4. Case# 76: cont… Cardiac Cath 10/19/2015: Right Dominance
SYNTAX Score was : 24
Cardiac Cath 10/19/2015: Right Dominance
I V +LM CAD with LVEF 60%
LM: 80% ostial
LAD: 70% ostial moderately calcified LAD, 60% D1
LCx: Non-obstructive
RCA: Non-obstructive
Hospital course: Pt had Heart Team discussion and decision about PCI was made due to COPD, spasticity and Syntax score <33
Plan Today:
IVUS guided intervention of LM and LAD with single DES crossover technique 4

5. Appropriateness Criteria for Coronary Revascularization

6. Issues Involving The Case
Current status of DAPT duration post DES
TCT Trials: ABSORB II, III/ China, LEADERS FREE
TUXEDO India

7. Issues Involving The Case
Current status of DAPT duration post DES
TCT Trials: ABSORB II, III/ China, LEADERS FREE, TUXEDO India

8. Trials of DAPT Duration After Stenting
Timing of aspirin only vs. DAPT
DAPT duration trials excluding
DAPT trial showed;
-Shorter DAPT has equivalent MACE
-Longer DAPT had higher bleeding
-No difference in ST between 2group
32,495 randomized patients!

9. Net Clinical Benefit of Longer DAPT in
Studies Evaluating a Period of DAPT ≤6 Months
Montalescot et al., J Am Coll Cardiol 2015;65:832

10. DAPT Study: 12 vs. 30 Months of DAPT
After DES
30-Month DAPT (n=5020)
12-Month DAPT (n=4921)
HR 0.71
p=<0.001
HR p=<0.001
HR p=0.001 %
HR p=0.05
HR p=<0.001
HR p=0.32
n=4710
n=4649
ST MACCE Death MI Stroke GUSTO bleeding
Def/Prob mod or severe
n=776
Mauri et al., N Engl J Med 2014;371:23

11. DAPT Study: 12 vs. 30 Months of DAPT
After BMS
30-Month DAPT (n=842)
12-Month DAPT (n=845)
p=0.72
p=0.002
p=0.74 %
p=0.07
p=0.83
p=0.24
p=0.74
n=790
n=776
n=776
ST MACCE Death MI Stroke GUSTO BARC Type 2+
Def/Prob mod-severe

12. DAPT Trial: EES PCI (47% of 9961, n=4682)
30-Month DAPT
p=0.42
12-Month DAPT
p=0.01
p=0.01
p=0.02 %
p=0.04
TCT 2015

13. Stent Thrombosis with First- and Second-Generation Drug-Eluting Stents
Giustino et al., J Am Coll Cardiol 2015;65:1298

14. OPTIDUAL Trial:
Twelve vs. 48 Months of Dual Antiplatelet Therapy After Drug-Eluting Stent Placement

15. OPTIDUAL Trial: Study Design
End of
the study
DES insertion
Randomization of patients free of MACCE or bleed
months months
ASPIRIN + CLOPIDOGREL
12 ± 3 months
ASPIRIN + CLOPIDOGREL
ASPIRIN ALONE
Follow-up (every 6 months between 12 and 48 months)

16. Patient Flow Chart (CONSORT)

17. Composite of death, MI, stroke, major bleeding
Primary Outcome:
Composite of death, MI, stroke, major bleeding

18. Post-Hoc Analysis of Ischaemic Outcomes: Death, Stroke, or MI

19. Meta-Analysis of RCTs Testing 12 Months vs Longer DAPT After DES
Death, MI or Stroke

21. Study Population
Thukkani et al., J Am Coll Cardiol 2015;66:1091

22. Long-Term Outcomes in Patients with DM Related
to Prolonging Clopidogrel After Coronary Stenting
Thukkani et al., J Am Coll Cardiol 2015;66:1091

24. Risk of MACE Comparing to Extended
DAPT vs Aspirin Alone
Udell et al., Eur Heart J August 31, 2015 EPub

25. Risk of Individual CV and Bleeding Endpoints Comparing Extended DAPT vs Aspirin Alone
Udell et al., Eur Heart J August 31, 2015 EPub

26. PEGASUS-TIMI 54 Trial: Primary Endpoints
Bonaca et al., N Engl J Med 2015;372:1791

27. PEGASUS-TIMI 54 Trial: Primary Endpoints
Bonaca et al., N Engl J Med 2015;372:1791

28. Ongoing Studies Examining Abbreviated Duration of DAPT
Montalescot et al., J Am Coll Cardiol 2015;66:832

30. Optimal Duration of Dual Antiplatelet Therapy After DES Implantation
Patient should be prescribed dual antiplatelet therapy for 6-12 months
Shortened Duration (new DES, <6M)
- Bleeding events within 6 months
- Need for non-cardiac surgery
- High bleeding risk
Anticoagulation need (e.g. Afib)
Renal failure
Co-morbidities at risk of bleeding (GI, Stroke, Cirrhosis, bleeding
diathesis, Frail)
Extended Duration (3yrs+)
- Thrombotic events within 6-12 mths
- First generation DES
- High ischemic risk
Prior MI, Diabetes
Multiple stents >3, LM stent
Bifurcation 2 stents
Prior Stent Thrombosis

31. Issues Involving The Case
Current status of DAPT duration post DES
TCT Trials: ABSORB II, III/ China, LEADERS FREE
TUXEDO India

32. ABSORB Trials: Absorb BVS
Everolimus/PDLLA (1:1) matrix coating
7 µm
Conformal coating
Controlled drug release similar to Xience CoCr-EES
PLLA Backbone
Semi-crystalline
Circumferential sinusoidal rings connected by linear links
Strut thickness 150 µm
Platinum markers in each end ring
Fully
Bioresorbable
Kereiakes, TCT 2015

33. ABSORB Trials: Metallic DES vs. Absorb BVS
Representative Human Images at 5 Years
Metallic DES
Absorb-Treated Artery

34. ABSORB II Trial: 2 Years Clinical Outcomes
ABSORB BVS (n=335)
XIENCE (n=166)
p=0.16
p=0.10 %
p=0.67
p=0.17
Chevalier, TCT 2015

35. ABSORB III Trial
Everolimus-Eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease

36. ABSORB III Trial: Absorb Program Objectives
A Series of Randomized Trials Designed to:
Demonstrate similar (non-inferior) results with ABSORB BVS compared to Xience CoCr-EES at 1 year
Demonstrate superior results with ABSORB BVS compared to Xience CoCr-EES between 1 and 5 years
Kereiakes, TCT 2015

37. ABSORB III Trial: Major Endpoints at 1 Year
Primary Endpoint: Target Lesion Failure (non-inferiority)
Cardiac death, or
Myocardial infarction attributed to the target vessel
(TV-MI), or
Peri-procedural MI: CK-MB >5x ULN w/i 48 hours
Ischemia-driven target lesion revascularization (ID-TLR)
Powered Secondary Endpoints (superiority)
Angina
All revascularization
Ischemia-driven target vessel revascularization (ID-TVR)
Kereiakes, TCT 2015

39. ABSORB III Trial: Study Flow and Follow-up
Randomized 2:1
N=2008 (ITT)
ABSORB N=1322
Xience
N=686
N=4 lost to follow-up
N=6 withdrew consent
N=6 lost to follow-up
N=3 withdrew consent
ABSORB
N=1312
Xience
N=677
12-month Follow-up
99.2% Complete
98.7% Complete
Kereiakes, TCT 2015

40. ABSORB III Trial: Acute Success
(N=1322)
(L=1385)
Xience
(N=686)
(L=713)
p-value
Device Success
94.3%
99.3%
<0.0001
Procedural Success
94.6%
96.2%
0.12
Device Success (lesion basis)
Successful delivery and deployment of study scaffold/stent at intended target lesion
Successful withdrawal of delivery system and final in-scaffold/stent DS <30% (QCA)
Procedure Success (patient basis)
Successful delivery and deployment of at least one study scaffold/stent at intended target lesion
No in-hospital (maximum 7 days) TLF

41. ABSORB III Trial: 1-Year TLF Components
Absorb (n=1322)
p=0.16
Xience (n=686)
p=0.18
p=0.50 %
p=0.13
p=0.29
TLF Cardiac death TV-MI ID-TLR Device Thrombosis
(def/prob)
Kereiakes, TCT 2015

42. ABSORB III Trial: Powered Secondary Endpoints
Xience
(N=686)
p-value
Angina
18.3%
18.4%
0.93
All Revascularization
9.1%
8.1%
0.50
ID-TVR
5.0%
3.7%
0.21
Kereiakes, TCT 2015

43. A Randomized Comparison of Everolimus-­Eluting Absorb Bioresorbable Vascular Scaffolds vs. Everolimus-Eluting Metallic Stents:
One-Year Angiographic and Clinical Outcomes from the ABSORB China Trial

44. ABSORB China Trial: Patient Flow and Follow-up (ITT)
Randomized
(N=480)
Absorb BVS
(N=241)
Absorb BVS
(N=241)
XIENCE V (N=239)
XIENCE V (N=239)
Withdrawal = 3
2 = Withdrawal
Absorb BVS
(N=238)
1-Year Clinical F/U (N=475; 99.0%)
XIENCE V (N=237)
XIENCE V (N=237)
Absorb BVS
(N=208)
1-Year Angio F/U (N=407; 84.8%)
XIENCE V (N=199)
ITT = 480 subjects (Absorb BVS: 241 and XIENCE V: 239)
PTE = 460 subjects (Absorb BVS: 228 and XIENCE V: 232)
Gao, TCT 2015

45. ABSORB China Trial: Primary Endpoint: In-Segment Late Loss at 1 Year (PTE)
Gao, TCT 2015

46. ABSORB China Trial: One Year Clinical Outcomes
Absorb BVS (n=241)
Xience V (n=239)
p=0.85
p=0.40 %
p=0.03
p=1.0
p=1.0
Gao, TCT 2015

48. LEADERS FREE Trial: Enrollment and Follow-Up
2,466 patients randomized
1,239 DCS
1,227 BMS
18 with no PCI
performed
16 with no PCI
performed
1,221 analyzed (modified ITT)
1,211 analyzed (modified ITT)
25 (2.0%) patients
withdrew before
12-month visit or
were lost to FU
22 (1.8%) patients
withdrew before
12-month visit or
were lost to FU
1,196 (98%) completed
12-month visit or died
1,189 (98.2%) completed
12-month visit or died
Urban et al., N Engl J Med Oct. 14, 2015 ePub

49. LEADERS FREE Trial: Components of Safety Endpoint
DCS (n=1221)
BMS (n=1211)
p=0.68
p=0.005
p=<0.001
p=0.01
p=0.19 %
p=0.70
Safety Endpoint Cardiac MI S T TLR Bleeding
death/MI/ST death (def/prob) (BARC 2-5)
Urban et al., N Engl J Med Oct. 14, 2015 ePub

50. One Year Clinical Results of TUXEDO India Trial
Paclitaxel Eluting Versus Everolimus Eluting Stents in Patients with Diabetes Mellitus and Coronary Artery Disease
One Year Clinical Results of TUXEDO India Trial

51. Tuxedo India Study Algorithm
Paclitaxel-eluting
TAXUS (n=914)
Everolimus-eluting
XIENCE (n=916)
1830 patients enrolled at 46 Indian sites
RVD ≥2.25 mm - ≤4 mm; Lesion length ≤34 mm
Upto 3 lesions with a maximum of 2 per epicardial vessel
Pre-rand: ASA ≥300 mg, clopidogrel ≥300 mg load unless on chronic Rx or Prasugrel 60 mg or Ticagrelor 180 mg
Randomized 1:1 TAXUS ElementTM : XIENCE PrimeTM
Pre-dilatation mandatory
Aspirin ≥75 mg QD for long term; clopidogrel 75mg QD for at least 12 months or Ticagralor 90 mg BD or Prasugrel 10 mg OD (if not at high risk for bleeding)
Clinical f/u only: 1, 6 months, 1 year and 2 years
Kaul, TCT 2015

52. Tuxedo India Study: PES vs EES in Diabetics
1 Year Endpoints
Taxus PES (n=914)
p=0.02
Xience EES (n=916)
p=0.002
p=0.004 %
p=0.75
p=0.002
Kaul, TCT 2015

53. Take Home Message: DAPT duration post DES and Absorb Trials
While 6-12 months DAPT duration post DES is sufficient in majority of PCI pts, there are subgroups who will benefit from prolonged DAPT (3+yrs) such as post MI, diabetics & pts with stent related issues. Prolonged DAPT despite lower MACE will be associated with significantly higher bleeding and slightly higher mortality
Bioresorbable vascular scaffold (ABSORB) trials have consistently shown numerically higher but non-significant TLF/TVF but higher stent thrombosis. It is very reassuring that current first generation BVS could favorably compare to the best (4-5th generation) metal DES. Hence we should favorably embrace this new technology with open mind

54. Question # 1
Following statements are generally true for short DAPT vs long DAPT except:
Lower ST with S-DAPT
Higher bleeding with L-DAPT
Slightly higher mortality with L-DAPT
Lower overall MACE with L-DAPT
Lower spontaneous MI with L-DAPT

55. Question # 2
Following subset of patient will benefit from prolonged DAPT except;
DES PCI in a multivessel diabetic pt
DES in pts with prior MI
DES in a pt with liver cirrhosis
DES thrombosis 6 mths after index PCI
Unexpanded stent with residual edge dissection

56. Question # 3
Following is the false statement from the ABSORB III trial of BVS at one year follow-up;
A. BVS TVF is not inferior to Xience DES
B. BVS pts had similar angina to Xience DES
C. BVS has smaller post-procedure MLD vs Xience DES
D. BVS has lower ST compared to Xience DES
E. BVS has non-statistically higher MI vs Xience DES

57. Question # 1 The correct answer is A
Following statements are generally true for short DAPT vs long DAPT except:
Lower ST with S-DAPT
Higher bleeding with L-DAPT
Slightly higher mortality with L-DAPT
Lower overall MACE with L-DAPT
Lower spontaneous MI with L-DAPT
The correct answer is A

58. Question # 2 The correct answer is C
Following subset of patient will benefit from prolonged DAPT except;
DES PCI in a multivessel diabetic pt
DES in pts with prior MI
DES in a pt with liver cirrhosis
DES thrombosis 6 mths after index PCI
Unexpanded stent with residual edge dissection
The correct answer is C

59. Question # 3 The correct answer is D
Following is the false statement from the ABSORB III trial of BVS at one year follow-up;
A. BVS TVF is not inferior to Xience DES
B. BVS pts had similar angina to Xience DES
C. BVS has smaller post-procedure MLD vs Xience DES
D. BVS has lower ST compared to Xience DES
E. BVS has non-statistically higher MI vs Xience DES
The correct answer is D