1. Complex Coronary Cases
Supported by:
Abbott Vascular
Boston Scientific Corporation
Medtronic, Inc.
AstraZeneca
St Jude’s Medical
Abiomed
Vascular solution
Bracco Diagnostic

2. Disclosures
Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, AngioScore, The Medicines Company, Daiichi Sankyo, Inc. and Lilly USA, LLC Annapoorna S. Kini, MBBS, FACC Nothing to disclose Sameer Mehta, MBBS, FACC Consulting Fees – The Medicines Company American College of Cardiology Foundation staff involved with this case have nothing to disclose

3. Nov 19th 2013 Case #17: WR, 73 yr M Presentation:
Patient presented with new onset exertional angina class II and positive high risk MPI for large infero-lateral and inferior ischemia. Cardiac cath on 10/21/13 revealed 3 V CAD (90% D1, 100% moderate size OM1 and 100% prox RCA with extensive collaterals from LAD/LCx) and LVEF 60%. Syntax score 21. Patient underwent EES DES x2 to D1. Pt still continued exertional angina despite MMT
Prior History:
Hypertension, Hyperlipidemia, +F/H
Medications: All once daily dosage
Metoprolol XL 50mg, ISMN 30mg, Losartan/HCTZ 50/25mg, ASA 81mg, Clopidogrel 75mg, Simvastatin 80mg 3

4. Case# 17: cont… Cardiac Cath 10/21/2013: Right Dominance
3 V CAD with LVEF 60%
Left Main: No obstruction
LAD: 30% pLAD and 90% calcific D1
LCx: 100% OM1 moderate size
RCA: 100% pRCA, distal vessel large and fills via LAD/LCx collaterals
Pt underwent PCI using 2 EES DES (2.5/23 and 2.5/12mm) of D1 with excellent results. Pt was discharged same day. Pt continued to have exertional angina despite MMT
Plan Today:
- PCI of CTO RCA using antegrade or retrograde approach 4

5. Appropriateness Criteria for Coronary Revascularization

6. Issues Involving The Case
Recent Trials of Coronary Bifurcation
Lesion PCI
Update in Duration & DAPT Interruption
post- DES

7. Issues Involving The Case
Recent Trials of Coronary Bifurcation
Lesion PCI
Update in Duration & DAPT Interruption
post- DES

8. Coronary Artery Bifurcation Lesion Interventional Techniques
Interventional Bifurcation Techniques
One Stent
Technique (OST)
Kissing Stent
Technique (SKS)
Crush Stent
Technique (CrST)
OST with SBR
Dilatation (SBT)
‘T’ Stent
Technique (TST)
Culotte Stent
Technique (CUT)

9. Bifurcation Lesion Intervention: 1 vs. 2 Stents
Technical Issues
One stent (ok & simple but may have difficulty
in rewiring or inserting second stent as bailout)
or 2 stents (guaranteed coverage of both lesions but higher MACE, TVR or ST in many studies)
If 2 stents; ?technique

10. A Randomized Clinical Study Comparing Double Kissing
Crush With Provisional Stenting for Treatment of Coronary Bifurcation Lesions: DK Crush II Study
Conventional (n= 185) %
p<0.001
DK Crush (n=185)
22.2
p=0.017
p=0.07
17.3
14.6
p=0.036
10.3
9.7
p=0.37
6.5
4.9
3.8
2.2
0.5
Main Vessel
Side Vessel
TVR
MACE ST
Angiographic Restenosis
Chen S et al, JACC 2011;57:914
Confidential Material 10

12. Nordic-Baltic Bifurcation Study IV: Patient Flow Chart
Provisional SB stening
n=221*
Two stent
n=229*
1 lost to FU
1 excluded due to protocol violation
1 withdrawal
Provisional
Completed 6M FU
n=220
Two stent
Completed 6M FU
n=227
Kumsars et al., TCT 2013

13. Nordic-Baltic Bifurcation Study IV:
Procedural Data
Provisional (n=221)
Two-stent (n=229) p
SB dilatation (%)
64.3
78.0 -
SB dilation or final kissing (%)
78.7
Final kissing balloon dilatation (%)
36.1
91.2
SB stented (%)
3.7
96.0
Culotte
65.6
T-stent
7.0
Other
26.4
Tx succesful* (%)
97.7
99.1 ns
*Residual stenosis <30% of MV + TIMI flow III in SB
Kumsars et al., TCT 2013

14. Nordic-Baltic Bifurcation Study IV:
Procedural Data
Provisional (n=221)
Two-stent (n=229) p
Procedure time (min)
73.9
92.6
<0.0001
Contrast volume (mL)
187
238
Flouroscopy time (min)
14.0
22.8
Tx succesful* (%)
97.7
99.1 ns
Procedural CK-MB>5x UPL** (%)
3.0
3.1
Procedural CK-MB>3x UPL** (%)
6.0
6.1
*Residual stenosis <30% of MV + TIMI flow III in SB
**Assessment possible in 327 patients
Kumsars et al., TCT 2013

15. Nordic-Baltic Bifurcation Study IV:
Event Free Survival Curve at 6 Months
1.8%
4.6%
p=0.09
Kumsars et al., TCT 2013

16. Nordic-Baltic Bifurcation Study IV: Individual Endpoints at 6 Months
Provisional (n=220)
p=0.11
Two-stent (n=227)
p=0.39 %
p=0.50
p=0.54
p=0.32
Kumsars et al., TCT 2013

18. TRYTON Bifurcation Trial: Study Design
Baseline Angiography – Eligible for Randomization
TRYTON side branch + DES (main vessel)
DES (main vessel) + Provisional side branch
N = 704
TVF
Primary Endpoint
Clinical F/U
at 9 months
Clinical F/U
at 9 months
% DS side branch
(N=374)
Secondary Endpoint
Angiographic F/U
at 9 months
Angiographic F/U
at 9 months
IVUS Cohort n~96
IVUS F/U
at 9 months
IVUS F/U
at 9 months
Leon et al., TCT 2013

19. TRYTON Bifurcation Trial: Patient Flow
Randomized
N=704
TRYTON + DES
N=355
Provisional + DES
N=349
9 Month Follow-up
N=681
TRYTON = 345
Provisional = 336
TRYTON
4= Lost to F/U
2= Patient withdrawal
4= Death
Provisional
6= Lost to F/U
5= Patient withdrawal
4= Death
Angiographic
N=326
TRYTON = 158
Provisional = 168
IVUS
N=94
TRYTON = 59
Provisional = 35
Clinical FU at 9 months = 97%
Angiographic FU at 9 months = 87%
Leon et al., TCT 2013

20. TRYTON Bifurcation Trial: TVF at 9 Months
Primary Endpoint
TRYTON
(N=355)
17.4%
Provisional
(N=349)
12.8%
Difference %
Upper 1-
Sided 95% CI %
Non-inferiority
p value =
Zone of non-inferiority pre-specified
margin = 5.5%
Non-inferior
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0 %
11.0
Primary Non-Inferiority Endpoint Not Met
Leon et al., TCT 2013

21. TRYTON Bifurcation Trial: TVF
Primary Endpoint ST
0.3%
0.6%
Provisional S (N=349)
TRYTON S (N=355
p =0.108
p =0.109 %
p =0.564
Non-Hierarchical
Leon et al., TCT 2013

22. TRYTON Bifurcation Trial: Additional Side Branch Stents Indications
Provisional
TRYTON %
Leon et al., TCT 2013

23. Secondary Endpoint TRYTON Bifurcation Study: SB %DS (In-segment) %
Secondary Superiority Endpoint Met
Leon et al., TCT 2013

25. COBIS II Registry: Independent Predictors of Side Branch Occlusion (Occurs in 8.4% cases)
Variable
Odds Ratio (95% CI) p
Pre-procedural %DS of the SB
≥50%
2.34 ( )
<0.001
Pre-procedural %DS of the
proximal MV ≥50%
2.34 (1/ )
0.03
SB lesion length
1.03 ( )
Acute coronary syndrome
1.53 ( )
0.02
Left main lesions
(vs. non-left main lesions)
0.34 ( )
0.005
Hahn et al., JACC 2013;62:1654

26. COBIS II Registry: Clinical Outcomes at 1-Yr F/U
Of the 187 SBr occlusion 31% of SBr occlusion remained post PCI
p=0.03
SB Occlusion (n=187)
No SB Occlusion (n=2040)
p=0.36 %
p=0.002
p=0.002
p=0.46
Hahn et al., JACC 2013;62:1654

27. Issues Involving The Case
Recent Trials of Coronary Bifurcation
Lesion PCI
Update in Duration & DAPT Interruption
post- DES

28. Optimal Duration of ADP Receptor Blockers Post DES Still Remain Unclear (Aspirin mg daily for life)
AHA/ACC
Updated Guidelines 2006
Cypher Stent
Launch
5/2003
AHA/ACC/SCAI
Updated Guidelines 2005
CURE, PCI-CURE – 2001
CREDO – 2002
(TAXUS stent 6 months post PCI)
(Cypher stent 3 months post PCI)
9-12 months
(FDA recommendations)
Clopido/Prasugrel/Ticag
should be
continued for 1 yr
or even longer if no
contraindications
BMS Era
DES Era
AHA/ACC PCI
Guidelines 2001
TAXUS Stent
Launch
3/2004
ESC 2005/ACC 2006
PCI Updated Guidelines
(12 months post PCI)
(1-12 months post BMS)
If not sure about DAPT compliance or has to be interrupted in
12M then BMS (Basket late) is safer & should be preferred

29. Randomized Trials of DAPT Duration
MACE
Bleeding %
REAL-LATE
PRODIGY
RESET

30. OPTIMIZE Trial: Study Design
Broad patient population
undergoing PCI with Endeavor ZES
RVD 2.5 mm – 4.0 mm
3 Months DAPT
N = 1560
N = 3120 patients
1:1 Randomization
33 Sites in Brazil
12 Months DAPT
N = 1560
Clinical endpoints
30-d.
3-mo.
6-mo.
12-mo.
18-mo.
24-mo.
36-mo.
Primary Endpoint: NACCE (Death / MI / Stroke / Major Bleeding) at 12 months
Secondary Endpoints: ARC defined ST, TVR, TLR, MACE, DAPT compliance, and major bleeding (REPLACE-2 & GUSTO definitions)
NACCE = Net Adverse Clinical and Cerebral Events
MACE is composed of Death, MI, Emergent CABG, TLR
Feres et al., Am Heart J 2012;164:810

31. OPTIMIZE Trial: DAPT Usage Time After Initial Procedure
3 Months DAPT (N=1563)
12 Months DAPT (N=1556)
Patients on DAPT (%)
Time After Initial Procedure
Feres et al., TCT 2013

32. OPTIMIZE Trial: NACCE at 1 Year
(All-Cause Death, MI, Stroke, Major Bleeding)
Cumulative Incidence
of NACCE (%)
Time After Initial Procedure (Months) 12 10 15 5 3 6 9
3M DAPT
12M DAPT
Non-inferiority
P-value = 0.002
Log-Rank P = 0.84
HR 1.03 (0.77 – 1.38)
6.0
5.8
Feres et al., TCT 2013

33. OPTIMIZE Trial: Other Clinical Events
at 1 Year
3 Months DAPT (N=1563)
12 Months DAPT (N=1556)
p=0.36
Events (%)
p=0.49
p=0.70
p=0.47
p=0.82
p=0.41
p=0.99
Feres et al., TCT 2013

34. ARCTIC-Interruption Study: Flow Chart
Rd#1: patients in ARCTIC
1181 were excluded
Rd#2: randomized by IVRS one year after stenting
635 DAPT FOR ITT ANALYSIS
624 SAPT FOR ITT ANALYSIS
6-18 months of Follow-up
death, MI, stroke, stent thrombosis, or urgent revascularization
Montalescot, TCT 2013

35. ARCTIC-Interruption Study: All Ischemic Endpoints
DAPT (N= 635)
SAPT (N= 624)
p=0.52 %
p=0.58
p=0.58
p=0.94
p=0.74
p=0.56
Primary ST or urg. Death Any death MI ST Stroke Urgent
Endpoint* revasc or MI or TIA revasc
*Any death, MI, ST, Stroke or TIA, Urgent revasc
Montalescot, TCT 2013

36. ARCTIC-Interruption Study: Key Safety Outcome
DAPT (N= 635)
p=0.03
SAPT (N= 624)
p=0.07 %
p=0.07
p=0.29
Montalescot, TCT 2013

37. What about DAPT discontinuation POST DES?
DAPT DURATION POST DES
Therefore DAPT duration of 6M (?3M) is now becoming the new 12M with newer generation DES
What about DAPT discontinuation POST DES?

38. After DAPT Interruption
Xience V USA Registry: Late ST Rates (30 D – 1 Year)
After DAPT Interruption
Overall
Standard (Low) Risk
Subsequent Late ST (ARC Def/Prob) (%)
0.49
0.37
0.26
0.16
13/ /1272
2/435 0/157
1/378 0/147
0/292 0/120
No Interruption
Interruption
After 30 Days
Interruption
After 90 Days
Interruption
After 180 Days
Krucoff, Hermiller, Sharma et al. JACC Intervent 2011;4:1298.

41. Modes of DAPT Cessation
Discontinuation
patients had discontinued DAPT as per recommendation of their physician who felt the patient no longer needed therapy
Interruption
patients had interrupted DAPT use on a voluntary basis and as guided by a physician due to (e.g. surgery)
DAPT was then reinstituted within 14 days
Disruption
patients had disrupted DAPT use due to bleeding or non-compliance.

42. PARIS Study: 2-Year K-M Plot of Any DAPT Cessation60
Two Years
(57.3%) 50 40
Cumulative Incidence, % 30
One Year
(23.3%) 20 10
30 Days
(2.9%) 6 12 18 24
Time since PCI, Months

43. PARIS Study: 2-Year Kaplan-Meier Plots of
Any Discontinuation, Interruption and Disruption 60
Discontinuation
Disruption
Interruption 50
40.8% 40
Cumulative Incidence, % 30 20
14.4%
10.5% 10 6 12 18 24
Time since PCI, Months

44. PARIS Study: DAPT Cessation and MACE
Events (n)
HR (95% CI)
On-DAPT
1.00 (Ref)
413
Discontinuation
0.63 (0.46, 0.86)
0.004 52
Interruption
1.41 (0.94, 2.12)
0.101 26
Disruption
1.50 (1.14, 1.97)
0.004 67
7.04 (3.31, 14.95)
2.17 (0.97, 4.88)
1.30 (0.97, 1.76)
0-7 Days
8-30 days
31+ days
<0.001
0.06
0.083 7 6 54
0.25
0.5 1 2 4 8 16
Hazard Ratio
Mehran et al., TCT 2013

45. PARIS Study: DAPT Cessation and Def/Prob
Stent Thrombosis
HR (95% CI) P
1.00 (Ref)
On-DAPT
0.39 (0.11, 1.35)
Discontinuation
0.64 (0.09, 4.82)
Interruption
2.58 (1.22, 5.46)
Disruption
0-7 Days
8-30 days
31+ days
15.94 (5.57, 45.58)
2.68 (0.36, 19.68)
1.35 (0.50, 3.64)
<0.001
0.334
0.551
0.25
0.5 1 2 4 8 16 32 64
Hazard Ratio
Mehran et al., TCT 2013

46. Dual Antiplatelet Therapy (DAPT) Study (clopidogre or prasugrel)
12 months
18 months
DES
n= 15245
BMS
n=5400
All patients on
aspirin + open-label
thienopyridine
therapy for
12 months
1:1 Randomization
at 12 months
50% of patients continue o dual antiplatelet therapy
(clopidogre or prasugrel)
50% of patients receive
aspirin + placebo
Total 33-month patient evaluation including additional 3-month follow-up
Mehran et al., TCT 2013

47. Take Home Message Trials of Bifurcation Lesions and DAPT duration/Interruption
Trials of large bifurcation lesion interventions have suggested favorable outcomes with 2S vs. 1S strategy without higher ST. Dedicated TRYTON bifurcation (BMS) stent was not superior to provisional stent approach
Trials of DAPT duration post DES support a shorter (3-6M) vs. 1+ year with lower bleeding and similar MACE. Hence 6M (?3M) DAPT duration should be routine post DES. Also physician directed DAPT interruption post DES is not associated with adverse outcomes

48. Question # 1
Which of the following trial compared 6M vs. 24M of DAPT duration:
PARIS Study
PRODIGY Trial
REAL LATE Trial
OPTIMIZE Trial
RESET Trial

49. Question # 2
TRYTON bifurcation trial showed the following superior results
over provisional stent strategy :
Lower TVR
Lower MI
Lower SBr %DS
Lower stent thrombosis
Higher CVA

50. Question # 3
Sidebranch occlusion post PCI is associated with the following except :
A. Higher mortality
B. Higher MI
C. Higher Stent thrombosis
D. Lower TVR
E. Higher MACE

51. Question # 1
Which of the following trial compared 6M vs. 24M of DAPT duration:
PARIS Study
PRODIGY Trial
REAL LATE Trial
OPTIMIZE Trial
RESET Trial
The correct answer is B as other trials have either 3M or 1Y DAPT duration

52. Question # 2
TRYTON bifurcation trial showed the following superior results
over provisional stent strategy :
Lower TVR
Lower MI
Lower SBr %DS
Lower stent thrombosis
Higher CVA
The correct answer is C as there was lower SBr % DS in the TRYTON stent arm vs. provisional stent arm
Leon M, TCT 2013

53. Question # 3
Sidebranch occlusion post PCI is associated with the following except :
A. Higher mortality
B. Higher MI
C. Higher Stent thrombosis
D. Lower TVR
E. Higher MACE
The correct answer is D as SBr occlusion is associated with higher TVR along with higher MACE and its other components
Hahn et al., JACC 2013;62:1654