2. Complex Coronary Cases
Supported by:
Abbott Vascular Inc
Boston Scientific Corp
Terumo Vascular Corp
Cardiovascular Science Inc
Abiomed Inc
Spectranetics Inc
B-Braun Inc
St Jude Medical inc

3. 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 Consulting Fees – Medtronic Inc

4. September 19th 2017 Case #99: BM, 82 yrs F
Presentation:
Presented with new onset CCS class III-IV angina and exertional dyspnea and a +CCTA for calcified 3 V CAD; no stress test done. A cardiac cath via Radial approach on sept 5th, 2017 revealed 3 V CAD: 60% prox RCA, heavily calcified 90% mid LAD and 80% D1 bifurcation lesion, 95% ulcerated LCx-OM1 lesion with Syntax score 22, and LVEF 60%. Pt underwent successful culprit vessel PCI of LCx-OM1 (2 Xience Alpine 3/23 & 2.5/15mm) and did well
Prior History: Hypertension, Hyperlipidemia, SAQ-7 score 23
Medications: All once daily dosage
ASA 81mg, Metoprolol XL 50mg, Rosuvastatin 40mg, Amlodipine 5mg, Enalapril 5mg, Levothyroxine 75mcg,
Clopidogrel 75mg & ISMN 30mg started after PCI 4

5. Case# 99: cont… Cardiac Cath 9/5/2017: Right Dominance
III V CAD and LVEF 60%
LM: No obstruction
LAD: Calcified 90% mid LAD, 80% D1 bifurcation lesion
LCx: 95% ulcerated OM1 lesion
RCA: 60-70% prox RCA lesion
SYNTAX Score: 22
Subsequent course: Pt underwent culprit vessel DES PCI of LCx-OM1 using 2 Xience Alpine DES and went home
Plan Today:
Planned for FFR guided staged PCI of LAD-D1 bifurcation lesion using rotational atherectomy of both branches and dedicated two stent strategy via femoral approach 5

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

7. Issues Involving The Case
Top Three interventional trials from ESC 2017:
BIOFLOW-V, RE-DUAL PCI, SYNTAX-II Trials
Studies of current trends in DAPT post ACS PCI:
PROMETHEUS, TOPIC, CHANGE DAPT Studies

8. Issues Involving The Case
Top Three interventional trials from ESC 2017:
BIOFLOW-V, RE-DUAL PCI, SYNTAX-II Trials
Studies of current trends in DAPT post ACS PCI:
PROMETHEUS, TOPIC, CHANGE DAPT Studies

10. BIOFLOW V Trial: Orsiro Ultra Thin Strut (BP SES) Stent System
Stent Material
L-605 Cobalt-Chromium
Strut thickness
60 μm*
Polymer material
Poly-L-lactic acid (PLLA)
Polymer type
Bioresorbable, asymmetric circumferential thickness; scission begins immediately with 24 month complete degradation
Passive coating
Amorphous silicon carbide
Antiproliferative drug
Sirolimus (1.4 μg/mm2), >80% eluted in first 90 days
*For 2.25 mm mm diameter stents, 80μm for >3.0 mm diameter stent
Kandzari et al., Lancet Aug 26, 2017 Epub

11. BIOFLOW V Trial: Randomized Clinical Trials Involving Orsiro BP SES
BIOFLOW II
BIOFLOW IV
BIOSCIENCE
BIO-RESORT
Location
Europe
Europe, Japan
Switzerland
Netherlands
Design
Randomised 2:1 vs. Xience Prime
Randomised 2:1 vs. Xience Prime/Xpedition
Randomised (1:1 vs Xience Prime)
Randomised (1:1:1, Orsiro, Synergy, Resolute Integrity)
Primary Endpoint
9 Months
12 Months
12 Months
Enrollment
452 (298 Orsiro, 154 Xience)
579 (387 Orsiro, 192 Xience)
2,119 (1,063 Orsiro, 1,056 Xience)
3,514 (1,172 Synergy, 1,169 Orsiro, 1,173 Resolute Integrity
Inclusion
1 to 2 de novo lesions
Separate arteries
All-comers
Follow-up
1, 6, 12 months and 2 to 5 year clinical
9 month clinical and angiographic (60 IVUS patients)
1, 6, 12 months and 2 to 5 year clinical
1 and 12 month and 2 to 5 year clinical
Kandzari et al., Lancet Aug 26, 2017 Epub

12. BIOFLOW V Trial Design

13. BIOFLOW V Trial: Patient Disposition
1,334 Patients enrolled
884 Allocated to BP SES
450 Allocated to DP EES
833 Evaluable for primary endpoint % Follow-up
427 Evaluable for primary endpoint % Follow-up
4,772 Patients screened
48 Did not complete a 12-month visit 24 Missed the 12-month visit
10 Withdrew consent
6 Were lost to follow-up 7 Died
1 Was exited for other reasons
29 Did not complete a 12-month visit 14 Missed the 12-month visit
7 Withdrew consent
2 Were lost to follow-up 6 Died
Kandzari et al., Lancet Aug 26, 2017 Epub

14. BIOFLOW V Trial: Procedural Characteristics
Angiographic/Procedural Results
BP SES (N=1,051 lesions)
DP EES (N=561 lesions)
Lesion length
13.3 ± 7.6
13.2 ± 7.7
Reference vessel diameter
2.6 ± 0.5
2.6 ± 0.6
No. target lesions/pt*
1.2 ± 0.4
1.3 ± 0.5
% diameter stenosis, pre
55.4 ± 13.3
55.9 ± 13.5
% diameter stenosis, post
7.1 ± 9.8
7.4 ± 9.8
Post-dilation performed
47.7%
46.2%
No. stents/lesion*
1.07 ± 0.3
1.13 ± 0.4
Stent length/lesion
20.8 ± 9.1
21.8 ± 10.5
Overlapping stents*
9.4%
15.0%
*P<0.05 for comparison
Kandzari et al., Lancet Aug 26, 2017 Epub

15. BIOFLOW V Trial: Procedural Outcomes
BP SES
DP EES
P value
Lesion success*
1102/1107 (99.5%)
579/583 (99.3%)
0.505
Device success†
1082/1107 (97.7%)
566/583 (97.1%)
0.415
Procedure success‡
827/881 (93.9%)
401/445 (90.1%)
0.019
*Lesion success defined as attainment of < 30% residual stenosis of the target lesion using any
percutaneous method.
†Device success defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only.
‡Procedure success defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only without occurrence of in-hospital major adverse cardiac events (MACE; composite of all-cause death, Q-wave or non-Q-wave MI, and any clinical-driven TLR).
Kandzari et al., Lancet Aug 26, 2017 Epub

16. BIOFLOW V Trial: 30 Day Outcomes
Orsiro BP SES (n=884)
Xience DP EES (n=450)
p=0.04
p=0.05 %
p=0.69
p=1.0
p=1.0
Kandzari et al., Lancet Aug 26, 2017 Epub

17. BIOFLOW V Trial: Primary Endpoint
12-Month TLF
Orsiro BP SES (n=884)
Xience DP EES (n=450)
p=0.04
p=0.02 %
p=0.67
p=0.12
Kandzari et al., Lancet Aug 26, 2017 Epub

18. BIOFLOW V Trial: Primary Endpoint
12-Month TLF
Kandzari et al., Lancet Aug 26, 2017 Epub

19. BIOFLOW V Trial: Stent Thrombosis
12 Month DAPT Adherence: 92.1% BP SES, 91.2% DP EES
BP SES (N=884)
DP EES (N=450)
P value
Stent Thrombosis
Any Stent Thrombosis
0.5%
1.2%
0.175
Definite
0.7%
0.694
Definite/Probable
Timing of Event (Definite/Probable ST)
Acute (≤ 24 hours)
0.1%
0.0%
1.000
Sub-acute (> 24 hours and ≤ 30 days)
0.2%
Late (> 30 days and ≤ 1 year)
0.264
Timing of Event (Any ST)
Sub-acute (> 24 rss and ≤ 30 days)
0.9%
0.047
Kandzari et al., Lancet Aug 26, 2017 Epub

20. Pooled Bayesian Analysis: BIOFLOW V, II and IV
Orsiro
BP SES
(n=1466)
Xience
DP EES
(n=742)
Rate difference
Posterior probability
TLF (Bayesian analysis)
Non-inferiority margin 3.85%
Superiority (post-hoc)
12-month rate, posterior mean ± estimate of SD (%), 95% CI
6.3±0.8
(4.9, 7.9)
8.9±1.2
(6.7, 11.4)
-2.6
(-5.5., 0.1)
100.0%
96.9%
Kandzari et al., Lancet Aug 26, 2017 Epub

23. RE-DUAL PCI: Antithrombotic Therapy for NVAF and PCI
Anticoagulant therapy
Antiplatelet therapy
BOTH anticoagulant and dual antiplatelet therapy =
Low shear stress thrombosis in left atrium
High shear stress thrombosis – platelet mediated in the arteries
‘triple therapy’
Anticoagulation superior to antiplatelet therapy
Dual antiplatelet therapy superior to ASA alone
High bleeding risk ?

24. RE-DUAL PCI: Study Design
Multicenter, Randomized, Open-Label Trial Following a PROBE Design

25. RE-DUAL PCI: Patients Randomized Based on
Age Group and Location

26. RE-DUAL PCI: Safety Endpoints Dual Therapy with Dabigatran (110mg)
Dual therapy with dabigatran (n=981)
Triple therapy with warfarin (n=981)
p=<0.001
p=0.002
p=0.06 %
Cannon et al., N Engl J Med Aug 27, 2017 Epub

27. RE-DUAL PCI: Safety Endpoints Dual Therapy with Dabigatran (150mg)
Dual therapy with dabigatran (n=763)
Triple therapy with warfarin (n=764)
p=0.002
p=0.009
p=0.03
p=0.05
p=0.02 %
Cannon et al., N Engl J Med Aug 27, 2017 Epub

28. RE-DUAL PCI: Efficacy Endpoints Dual Therapy with Dabigatran (110mg)
Dual therapy with dabigatran (n=981)
Composite efficacy Thromboembolic Death MI Stroke Definite ST
endpoint events or death %
Triple therapy with warfarin (n=981)
p=0.30
p=0.07
p=0.56
p=0.09
p=0.48
p=0.15
Cannon et al., N Engl J Med Aug 27, 2017 Epub

29. RE-DUAL PCI: Efficacy Endpoints Dual Therapy with Dabigatran (150mg)
Dual therapy with dabigatran (n=763)
Composite efficacy Thromboembolic Death MI Stroke Definite ST
endpoint events or death %
Triple therapy with warfarin (n=764)
p=0.44
p=0.88
p=0.44
p=0.61
p=0.85
p=0.98
Cannon et al., N Engl J Med Aug 27, 2017 Epub

30. RE-DUAL PCI: Additional Individual Thromboembolic Endpoints
Dabigatran
110 mg dual therapy (n=981) (%)
Warfarin triple therapy (n=981)
(%)
D110 DT vs Warfarin TT
150 mg dual therapy (n=763) (%)
Warfarin triple therapy (n=764) HR
(95% CI)
P Value
All-cause death
5.6
4.9
1.12 ( )
0.56
3.9
4.6
0.83 ( )
0.44
Stroke
1.7
1.3
1.30 ( )
0.48
1.2
1.0
1.09 ( )
0.85
Unplanned revasc
7.7
7.0
1.09 ( )
0.61
6.7
6.8
0.96 ( )
0.83 MI
4.5
3.0
1.51 ( )
0.09
3.4
2.9
1.16 ( ) ST
1.5
0.8
1.86 ( )
0.15
0.9
0.99 ( )
0.98

31. RE-DUAL PCI: Primary Endpoint and Secondary Efficacy Endpoint
Primary Endpoint in Dual Therapy Grp (110 mg) vs Triple Therapy Grp
Primary Endpoint in Dual Therapy Grp (150 mg) vs Triple Therapy Grp
Secondary Efficacy in Dual Therapy Grp (Combined) vs Triple Therapy Grp
Cannon et al., N Engl J Med Aug 27, 2017 Epub

34. SYNTAX Score II Calculator

35. SYNTAX II Trial Flowchart
Escaned et al., Eur Heart J 2017 Epub Aug 2017

36. SYNTAX II Trial: PCI Procedure Flowchart
Patient included in the SYNTAX II study
iFR in all intended to treat stenoses
iFR <0.86
iFR
iFR >0.93
iFR >0.93
FFR ≤0.80
FFR >0.80
Stenosis treated with SYNERGYTM EES
Stenosis not treated
IVUS optimization
Optimal medical therapy with strict LDL control
(≤ 1.8mmol/L)

37. SYNTAX II Trial: ID-Revasc Flowchart
Escaned et al., Eur Heart J 2017 Epub Aug 2017

38. SYNTAX Score II Trial SYNTAX Score II PCI 30.2 ± 8.6 30.6 ± 8.7 0.528
SYNTAX II SYNTAX I PCI arm P
Components of the SYNTAX Score II
Age
66.7 ± 9.7
66.7 ± 9.1
0.99
Gender (Male)
93.2%
93.0%
0.93
Cr Clearance (ml/min)
82.0 ± 26.9
87.3 ± 28.5
0.008
Ejection Fraction (%)
58.1 ± 8.3
61.8 ± 11.3
<0.001
Peripheral Vascular Disease
7.7%
9.5%
0.37
COPD
10.8%
12.7%
0.42
Anatomic SYNTAX Score
20.3 ± 6.4
22.8 ± 8.7
SYNTAX Score II PCI
30.2 ± 8.6
30.6 ± 8.7
0.528
Predicted 4-yr mortality PCI (%)
8.9 ± 8.8%
9.2 ± 8.7%
0.640
SYNTAX Score II CABG
29.1 ± 10.4
29.1 ± 9.6
1.0
Predicted 4-yr mortality CABG (%)
9.0 ± 9.3
8.5 ± 8.1
0.440

39. SYNTAX II Trial: 1 Year Clinical Outcomes
Between SYNTAX II Cohort and SYNTAX I PCI
SYNTAX II (n=454)
SYNTAX I PCI (n=315)
p=0.006
p=0.05
p=0.02
p=0.007
p=0.71
p=0.43 %
Escaned et al., Eur Heart J 2017 Epub Aug 2017

40. SYNTAX II Trial: 1 Year Clinical Outcomes
Among Patients of SYNTAX II and SYNTAX I PCI
MACCE MI
Any Repeat Revasc
Escaned et al., Eur Heart J 2017 Epub Aug 2017

41. SYNTAX II Trial: Impact of Intracoronary
Physiology on PCI
Lesion treatment after iFR/FFR interrogation (n=1177)
Lesions treated per patient (n) in SYNTAX II and SYNTAX I
Cases of three-vessel PCI (%) in SYNTAX II and SYNTAX I
p=<0.001
p=<0.001
PCI
deferred
PCI
performed % %
SYNTAX II
Escaned, ESC 2017

42. SYNTAX II Trial: Treatment of Chronic Total Occlusions (CTO)
CTO PCI procedural success rate in SYNTAX II: 87%
CTO revascularization in SYNTAX II and SYNTAX I
Success
p=<0.001
Failed
87% %
13%
SYNTAX II CTO PCI
Escaned, ESC 2017

43. SYNTAX II Trial: Use of IVUS
IVUS use in SYNTAX II and SYNTAX I (patient level, % of cases)
Patient level
Lesion level
p=<0.001
84.1%
76.4% %
IVUS
No IVUS
Post-implantation IVUS led to further optimization of the stented lesion in 30.2%
Escaned, ESC 2017

44. SYNTAX II Trial: Exploratory Endpoint
MACCE PCI vs CABG
Escaned, ESC 2017

45. SYNTAX II Trial: MACCE SYNTAX II and SYNTAX I PCI/CABG
Escaned, ESC 2017

47. Issues Involving The Case
Top Three interventional trials from ESC 2017:
BIOFLOW-V, RE-DUAL PCI, SYNTAX-II Trials
Studies of current trends in DAPT post ACS PCI:
PROMETHEUS, TOPIC, CHANGE DAPT Studies

48. Days after Randomization
TRITON Trial
PLATO Trial 15 10 5
Primary Efficacy End Points
12.1
Clopidogrel
9.9 %
Prasugrel
Key Safety End Points
2.4
1.8
Days after Randomization
Both these new P2Y inhibitors became
ACC/AHA Class I agents in ACS PCI
Wiviott et al. N Engl J Med 2007;357:2001

50. PROMETHEUS Cohort by Clinical Presentation
Prasugrel Use by Clinical Presentation
Unstable angina NSTEMI STEMI
(n=11,216) (n=5,412) (n=3,285) %
NSTEMI
(n=5412)
Baber, Mehran et al., Am Heart J 2017;188:73

51. PROMETHEUS Study: Baseline Clinical Characteristics
by Treatment Group

52. PROMETHEUS Study: Baseline Procedural
Characteristics by Treatment Group
Baber, Mehran et al., Am Heart J 2017;188:73

53. PROMETHEUS Study: Frequency of Prasugrel Use by Number of Thrombotic Risk Factors%
Baber, Mehran et al., Am Heart J 2017;188:73

54. PROMETHEUS Study: Cumulative Rate of MACE and Bleeding by Treatment Group
Baber, Mehran et al., Am Heart J 2017;188:73

57. TOPIC Study Design
Cuisset et al., Eur Heart J March 2017 Epub

58. TOPIC Study Clinical Outcomes
Incidence of the Primary Endpoint at 1 Year
Incidence of BARC ≥2 Bleeding at 1 Year
Cuisset et al., Eur Heart J March 2017 Epub

59. TOPIC Study Endpoints at 1 Year
Switched DAPT (n=322)
Unchanged DAPT (n=323)
p=<0.01
p=<0.01
p=<0.01
p=0.36 %
p=0.78
p=0.32
p=0.18
Cuisset et al., Eur Heart J March 2017 Epub

62. CHANGE DAPT Study Flowchart
Zocca et al., EuroIntervention Aug 2017 Epub

63. CHANGE DAPT Study: Baseline Characteristics
Zocca et al., EuroIntervention Aug 2017 Epub

64. CHANGE DAPT Study: Procedural Characteristics and Medication
Zocca et al., EuroIntervention Aug 2017 Epub

65. CHANGE DAPT Study: Cumulative Incidence for Primary Endpoint NACCE at 1 Year
Zocca et al., EuroIntervention Aug 2017 Epub

66. CHANGE DAPT Study: Cumulative Incidence for Death, MI, Stroke Major Bleeding at 1 Year
Zocca et al., EuroIntervention Aug 2017 Epub

67. CHANGE DAPT Study: One Year Clinical Outcomes
Clpidogrel period (n=1,009)
Ticagrelor period (n=1,053) %
p=0.02
p=0.65
p=0.18
p=0.05
p=0.60
p=0.21
Zocca et al., EuroIntervention Aug 2017 Epub

68. CHANGE DAPT Study: One Year Clinical Outcomes for the Sensitivity Analysis
Clpidogrel period (n=877)
Ticagrelor period (n=894) %
p=0.12
p=0.74
p=0.39
p=0.02
p=0.06
p=0.83
p=0.92
Zocca et al., EuroIntervention Aug 2017 Epub

70. Take Home Message: Top Interventional Trials from ESC and Changing DAPT use in ACS PCI
Ultrathin strut with biodegradable polymer (Orsiro) is the new frontier in the latest DES development. DAPT using NOAC (Dabigatran) is superior to triple therapy of warfarin+DAPT post PCI in NVAF pts. Current generation stents and improved PCI technology as shown in SYNTAX II study, results in superior outcomes of PCI compared to Syntax I PCI gp and similar to Syntax CABG group.
Despite the ACC Class I recommendation for use of newer potent P2Y12 inhibitors, their use in real world is extremely low largely because of concerns of bleeding. In the current era with use of better stents, ischemic outcomes are lower with any DAPT but higher bleeding with Prasugrel and Ticagrelor and hence their use could be limited to selected pts and for a shorter duration.

71. Question # 1
Following is the main finding of BIOFLO V trial comparing Orsario vs Xience DES:
Lower peri-procedural MI with Orsiro
Lower ST with Orsiro
C. Lower TLR with Orsiro
Lower death rate with Orsiro
E. Similar TLF with Orsiro

72. Question # 2 SYNTAX II study concluded the following results;
Current PCI outcomes are similar to Syntax I PCI gp
Current PCI outcomes are inferior to Syntax I PCI gp
Current PCI outcomes are similar to Syntax CABG gp
Current PCI outcomes are superior to Syntax I CABG gp
Current PCI results in lower death rates vs any Syntax I gp

73. Question # 3
Following statements truly reflects the current data on the use of potent P2Y12 inhibitors after ACS PCI in real practice:
A. There is perceived and higher ST with Clopidogrel use
B. There is higher MACE rates with Clopidogrel use
C. There is higher ST rates with potent P2Y12 inhibitors
D. There is higher bleeding with use of potent P2Y12 inhibitors
E. They are frequently used in post ACS PCI currently

74. Question # 1 The correct answer is A
Following is the main finding of BIOFLO V trial comparing Orsario vs Xience DES:
Lower peri-procedural MI with Orsiro
Lower ST with Orsiro
C. Lower TLR with Orsiro
Lower death rate with Orsiro
E. Similar TLF with Orsiro
The correct answer is A

75. Question # 2 The correct answer is C
SYNTAX II study concluded the following results;
Current PCI outcomes are similar to Syntax I PCI gp
Current PCI outcomes are inferior to Syntax I PCI gp
Current PCI outcomes are similar to Syntax CABG gp
Current PCI outcomes are superior to Syntax I CABG gp
Current PCI results in lower death rates vs any Syntax I gp
The correct answer is C

76. Question # 3 The correct answer is D
Following statements truly reflects the current data on the use of potent P2Y12 inhibitors after ACS PCI in real practice:
A. There is perceived and higher ST with Clopidogrel use
B. There is higher MACE rates with Clopidogrel use
C. There is higher ST rates with potent P2Y12 inhibitors
D. There is higher bleeding with use of potent P2Y12 inhibitors
E. They are frequently used in post ACS PCI currently
The correct answer is D