Complex Coronary Cases

Supported by:

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Abbott Vascular

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Boston Scientific Corporation

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Medtronic, Inc.

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AstraZeneca

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St Jude’s Medical

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Abiomed

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Vascular solution

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Bracco Diagnostic

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

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

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

Appropriateness Criteria for Coronary Revascularization

Issues Involving The Case

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Recent Trials of Coronary Bifurcation Lesion PCI

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Update in Duration & DAPT Interruption post- DES

Issues Involving The Case

•

Recent Trials of Coronary Bifurcation Lesion PCI

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Update in Duration & DAPT Interruption post- DES

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)

Bifurcation Lesion Intervention: 1 vs. 2 Stents

Technical Issues

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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

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 MACE 0.5

2.2

ST 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% Non inferiority 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

%

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

%

TRYTON Bifurcation Trial:

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

•

Recent Trials of Coronary Bifurcation Lesion PCI

•

Update in Duration & DAPT Interruption post- DES

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

OPTIMIZE Trial: Study Design

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

OPTIMIZE Trial: NACCE at 1 Year

(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

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?

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

13/3500 2/1272 No Interruption 0.49

0 2/435 0/157 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.

Modes of DAPT Cessation

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Discontinuation

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patients had discontinued DAPT as per recommendation of their physician who felt the patient no longer needed therapy

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Interruption

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patients had interrupted DAPT use on a voluntary basis and as guided by a physician due to (e.g. surgery)

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DAPT was then reinstituted within 14 days

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Disruption

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patients had disrupted DAPT use due to bleeding or non-compliance.

PARIS Study: 2-Year K-M Plot of Any DAPT Cessation 60 50 40 30 20 10 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

26 67 7 6 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