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

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

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

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

Appropriateness Criteria for Coronary Revascularization

Issues Involving The Case
•
•

Issues Involving The Case
•

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)

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

A Randomized Clinical Study Comparing Double Kissing
Crush With Provisional Stenting for Treatment of Coronary
Bifurcation Lesions: DK Crush II Study
% p<0.001
22.2
Conventional (n= 185)
DK Crush (n=185) 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
Main Vessel Side Vessel
Angiographic Restenosis
TVR
0.5
2.2
ST MACE
Chen S et al, JACC 2011;57:914

Nordic-Baltic Bifurcation Study IV:
Patient Flow Chart
Nordic Baltic Bifurcation study IV n=450
Provisional SB stening n=221*
Two stent n=229*
1 withdrawal
1 lost to FU
1 excluded due to protocol violation
Provisional
Completed 6M
FU n=220
Two stent
Completed 6M
FU n=227
Kumsars et al., TCT 2013

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

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

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

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

TRYTON Bifurcation Trial: Study Design
N = 704
TVF
Primary Endpoint
% DS side branch
(N=374)
Secondary Endpoint
IVUS Cohort n~96
Leon et al., TCT 2013

TRYTON Bifurcation Trial: Patient Flow
TRYTON
4= Lost to F/U
2= Patient withdrawal
4= Death
Provisional
6= Lost to F/U
5= Patient withdrawal
4= Death
Leon et al., TCT 2013

TRYTON Bifurcation Trial: TVF at 9 Months
Primary Endpoint
TRYTON
(N=355)
17.4%
Provisional
(N=349)
12.8%
Difference 4.6%
Upper 1-
Sided 95% CI 10.3%
Zone of non-inferiority pre-specified margin = 5.5%
Noninferiority
p value
= 0.4167
0 1.0
2.0
Non-inferior
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

%
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

%
Additional Side Branch Stents Indications
Provisional
TRYTON
Leon et al., TCT 2013

TRYTON Bifurcation Study: SB %DS (In-segment)
Secondary Endpoint
p=0.002
%
Secondary Superiority Endpoint Met
Leon et al., TCT 2013

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 (1.59-3.43) <0.001
Pre-procedural %DS of the proximal MV ≥50%
2.34 (1/57-3.50) 0.03
SB lesion length
Acute coronary syndrome
Left main lesions
(vs. non-left main lesions)
1.03 (1.003-1.06)
1.53 (1.06-2.19)
0.34 (0.16-0.72)
<0.001
0.02
0.005
Hahn et al., JACC 2013;62:1654

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

Issues Involving The Case
•

Optimal Duration of ADP Receptor Blockers Post DES
Still Remain Unclear (Aspirin 81-325 mg daily for life)
AHA/ACC
Updated Guidelines 2006
CURE, PCI-CURE – 2001
CREDO – 2002
9-12 months
Cypher Stent
Launch
5/2003
AHA/ACC/SCAI
Updated Guidelines 2005
(TAXUS stent 6 months post PCI)
(Cypher stent 3 months post PCI)
BMS Era DES Era
(FDA recommendations)
Clopido/Prasugrel/Ticag should be continued for 1 yr or even longer if no contraindications
AHA/ACC PCI
TAXUS Stent
Guidelines 2001
Launch
3/2004
(1-12 months post BMS)
ESC 2005/ACC 2006
PCI Updated Guidelines
(12 months post PCI)
If not sure about DAPT compliance or has to be interrupted in
12M then BMS (Basket late) is safer & should be preferred

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

3 Months DAPT
N = 1560
Clinical endpoints
30-d.
Broad patient population undergoing PCI with Endeavor ZES
RVD 2.5 mm – 4.0 mm
N = 3120 patients
1:1 Randomization
33 Sites in Brazil
12 Months DAPT
N = 1560
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

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

(All-Cause Death, MI, Stroke, Major Bleeding)
15
3M DAPT
12M DAPT
10
Non-inferiority
P-value = 0.002
Log-Rank P = 0.84
HR 1.03 (0.77
– 1.38)
6.0
5.8
5
0
0 3 6 9
Time After Initial Procedure (Months)
12
Feres et al., TCT 2013

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

ARCTIC-Interruption Study: Flow Chart
Rd#1: 2440 patients in ARCTIC
1181 were excluded
Rd#2: 1259 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

ARCTIC-Interruption Study: All Ischemic Endpoints
p=0.57
DAPT (N= 635)
SAPT (N= 624)
p=0.52
% p=0.58
p=0.58
p=0.94
p=0.56
p=0.74
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

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

•
6M

Xience V USA Registry: Late ST Rates (30 D – 1 Year)
After DAPT Interruption
2
Overall
Standard (Low) Risk
1.5
1
0.5
0
0.37
0.16
0.49
0
13/3500 2/1272 2/435 0/157
No Interruption Interruption
After 30 Days
0.26
0
1/378 0/147
Interruption
After 90 Days
0 0
0/292 0/120
Interruption
After 180 Days
Krucoff, Hermiller, Sharma et al. JACC Intervent 2011;4:1298.

• 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.

PARIS Study: 2-Year K-M Plot of Any DAPT Cessation
30
20
10
60
50
40
0
30 Days
(2.9%)
One Year
(23.3%)
6 12
Time since PCI, Months
18
Two Years
(57.3%)
24

PARIS Study: 2-Year Kaplan-Meier Plots of
Any Discontinuation, Interruption and Disruption
30
20
10
60
50
40
0
Discontinuation
Disruption
Interruption
6 12
Time since PCI, Months
18
40.8%
14.4%
10.5%
24

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

PARIS Study: DAPT Cessation and Def/Prob
Stent Thrombosis
HR (95% CI)
1.00 (Ref)
P
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
15.94 (5.57, 45.58) <0.001
8-30 days
2.68 (0.36, 19.68) 0.334
31+ days
1.35 (0.50, 3.64) 0.551
0.25 0.5 1 2 4 8 16 32 64
Hazard Ratio
Mehran et al., TCT 2013

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

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

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

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

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

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

Question # 2
TRYTON bifurcation trial showed the following superior results over provisional stent strategy :
A. Lower TVR
B. Lower MI
C. Lower SBr %DS
D. Lower stent thrombosis
E. 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

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