Philippe Généreux, MD

Columbia University Medical CenterCardiovascular Research Foundation

New York City

The TRYTON StentDedicated Bifurcation Stent in Coronary

Bifurcation

TCT 2016, Washington

Disclosure Statement of Financial Interest

Philippe Généreux, MDWithin the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

• Grant/Research Support

• Consulting Fees/Honoraria

• Major Stock Shareholder/Equity

• Boston Scientific, CSI, TRYTON Medical

• Abbott Vascular, CSI, Edwards Lifesciences, TRYTON Medical, Soundbite Medical Inc., SIG.NUM, SARANAS

• Soundbite Medical Inc., SIG.NUM

Bifurcation Lesions Still a Challenge

• Require more time, anxiety, skill, and equipment (cost)

• Increased complicationsperi-­procedural MIs,stent thrombosis, andrestenosis

• Suboptimal angiographic outcomes (esp. side branch ostium)

Randomized Bifurcation Stent Studies(NORDIC, BBC ONE, CACTUS)

TRYTON Side Branch Stent

Transition Zone

Side Branch Zone

Main Branch Zone

8 mm 4.5 mm 6.5 mm

Tryton is a Cobalt alloy bare metal stent

Tryton Side Branch Stent Sizes

Tryton Deployment Sequence

Tryton positioned and deployed after pre-­dilatation

(secures and protects side branch)

Main vessel treated with approved DES through main

vessel portion of Tryton

Kissing balloon post-­dilatation to

insure complete lesion & ostium coverage

TRYTON Pivotal RCT

Généreux et al. J Am Coll Cardiol 2015;;65:533–43

Tryton Study Design

DES (main vessel) + Provisional side branch

Baseline Angiography – Eligible for RandomizationTrue bifurcation with SB≥ 2.5mm by visual estimation

Angiographic F/Uat 9 months

Clinical F/U at 9 months

ê

ê

ê

ê

ê

% DS side branchn~374

Tryton side branch + DES (main vessel)

êê

TVFPrimary Endpoint

ê

N = 704

IVUS F/Uat 9 months

ê

IVUS Cohort n~96

Clinical F/U at 9 months

Angiographic F/Uat 9 months

IVUS F/Uat 9 months

TRYTON Pivotal RCT Primary Non-­Inferiority Endpoint

Not Met%

12.8

0

10.7

3.6

17.4

0

15.1

4.7

02468101214161820

TVF Cardiac Death Target Vessel MI Clinically Driven TVR

Non Hierarchical

P= 0.11P = 0.11

P =0.56

ProvisionalTryton

Généreux et al. J Am Coll Cardiol 2015;;65:533–43

38.631.6

0

10

20

30

40

50

60

P=0.002

ProvisionalTryton

Side Branch %DS (In-­segment)Secondary Endpoint

%

Secondary Superiority Endpoint MetAngiographic Cohort n=326

Généreux et al. J Am Coll Cardiol 2015;;65:533–43

14

33

49

152

164

104

66 68

2410 11 60

20

40

60

80

100

120

140

160

180

≥ 2.25 mm:41% of ITT lesions

Side Branch RVD (Core Lab)#

Frequency

Pre Procedure Side Branch Size

TRYTON Large SBs Sub-­Analysis:Side Branches ≥2.25mm

Généreux et al. Catheter Cardiovasc Interv. 2015

10.315.6

9.212.1

21.7

11.3

19.2

9.25.5 4.33.1 3.5

0

5

10

15

20

25

30

35

<2.25 mm ≥2.25 mm <2.25 mm ≥2.25 mm <2.25 mm ≥2.25 mm

Provisional TRYTON StentEvent Rate (%)

44/20320/195 22/141 18/195 17/141 6/195 6/13916/141 39/203 13/141 11/201 5/141

Side Branch Size

TVF

OR =2.42[1.37,4.28]

OR =0.69 [0.35,1.38]

P for interaction=0.006

Target Vessel MI

OR =2.34[1.29,4.25]

OR =0.74 [0.35,1.59]

P for interaction=0.02

Clinically Driven TVR

OR =1.82[0.66,5.03] OR =0.81

[0.24,2.73]

P for interaction=0.32

Généreux et al. Catheter Cardiovasc Interv. 2015

40.6

32.130.4

22.2

0

5

10

15

20

25

30

35

40

45

SB % Diameter Stenosis SB Binary Restenosis

ProvisionalTryton

P = 0.004

P = 0.26

Angiographic Outcomes (QCA)Side Branch ≥ 2.25 mm 9 Months

Provisional N=81Tryton N=64

%

Généreux et al. Catheter Cardiovasc Interv. 2015

TRYTON Confirmatory Study

TRYTON Confirmatory StudyRationale

• To prospectively confirm the safety (periprocedural MI) of the TRYTON dedicated bifurcation stent in the treatment of true bifurcation lesions involving large side branches (≥2.25mm by QCA analysis)

TRYTON Confirmatory Study Angiographic Inclusion Criteria: No Change

• Single de novo “true” bifurcation lesion • Native coronary artery • Medina 1.1.1, 1.0.1, or 0.1.1 by visual estimation

• Symptoms or objective evidence of ischemia• Vessel diameter: • Main branch: ≥ 2.5 mm and ≤ 4.0 mm;;• Side branch: ≥ 2.5 mm and ≤ 3.5 mm

• Lesion length: • Main vessel ≤ 28 mm;; Side branch ≤ 5 mm

• Multi-­vessel disease and staging allowed• Enrolment allowed after successful treatment of ≤ 2 non-­complex non-­target lesions

TRYTON Confirmatory StudyReview Clinical Selection Criteria/Informed Consent

Baseline AngiographyReview Angiographic Selection Criteria

N=133 patients TRYTON stent side branch first stepDES in Main branch second step

Primary End point: Periprocedural MI >3X URL CK-­MB 48hrs post PCI

Clinical F/U: 30 days and 1 year

ITT when TRYTON stent enters the guide catheter

TRYTON Confirmatory StudyPerformance Goal: Sample Size Calculation

• Powered Endpoint: • Peri-­procedural MI 3x CK-­MB @48hrs • Observed Rate in IDE provisional: 11.9% • Power: 90% • Delta: 6.0%• 1-­sided 95% upper confidence bound

• Performance Goal: 17.9%• N = 133

• Anticipated 4% lost of follow-­up• CK-­MB missing, RVD <2.25mm

TRYTON Confirmatory Study:Study Recruitment

28 Investigational CentersUS =13, OUS =15

12 months enrolment

Baseline Characteristics: DemographicConfirmatory Study Randomized IDE ≥2.25mm

TRYTON(N=133)

TRYTON(N=146)

Provisional(N=143)

Age (years) 65.6±9.5 64.5±10.7 65.2±9.2Male 69.9% 79.5% 81.8%MI 32.3% 29.7% 40.4%PCI 39.8% 37.0% 43.4%CABG 2.3% 3.4% 3.5%TIA / CVA 6.8% 8.9% 5.7%CHF 6.0% 1.4% 0.0%Diabetes Mellitus 25.8% 25.3% 28.7%Hypertension * 82 %* 68.5% * 76.8%Hypercholesterolemia 71.2% 72.2% 77.0%Current Smoking 21.1% 17.1% 15.5%Atrial Fibrillation 7.5% 12.3% 8.4%* P<0.05

Baseline Characteristics: PresentationConfirmatory Study Randomized IDE ≥2.25mm

TRYTON (N=133)

TRYTON(N=146)

Provisional(N=143)

Recent MI NA 8.9% 11.2%Angina TypeStable 73.7% 74.0% 68.5%Unstable 18.0% 19.2% 23.8%

CCS ClassI 15.3% 15.7% 17.0%II 55.1% 56.9% 58.5%III 27.6% 24.5% 20.2%IV 2.0% 2.9% 4.3%

Ischemia + 64.2% 61.7% 63.9%LVEF 56.3±9.5 57.1±9.4 56.8±10.7

Medina Classification: Angio Core Laboratory Confirmation

T: 0%P: 2.8%Con: 0%

“True”Bifurcation

T: 88.3%P: 86.8%Con: 100%

T: 45.9%P: 39.9%Con: 50.4%

T: 16.4%P: 16.8%Con: 15.0%

T: 26.0%P: 30.1%Con: 34.6%

T: 2.1%P: 5.6%Con: 0%

T: 4.1%P: 2.8%Con: 0%

T: 5.5%P: 2.1%Con: 0%

P=Provisional T=Tryton Con=Confirmatory

Baseline Characteristics: Main BranchConfirmatory Study Randomized IDE ≥2.25mm

TRYTON(N=133)

TRYTON(N=146)

Provisional(N=143)

Vessel LocationLAD 75.2% 71.2% 65.7%LCX 20.3% 19.9% 25.2%RCA 3.8% 8.9% 9.1%Lesion LocationOstial 10.5% 8.2% 7.0%Proximal 50.4% 44.5% 44.1%Mid 15.8% 20.5% 18.2%Distal 23.3% 26.7% 30.8%RVD (mm) 3.12±0.37 3.09±0.35 3.06±0.34Lesion Length (mm) 17.23±7.89 16.14±6.84 16.05±6.53Morphologyangulation ≥45o 8.3% 11.0% 9.8%thrombus 1.5% 0.0% 1.4%calcification – mod/severe 29.3% 13.7% 18.9%TIMI Flow (baseline) < 3 15.0% 7.5% 14.0%

Baseline Characteristics: Side Branch

Confirmatory Study Randomized trial ≥2.25mm TRYTON(N=133)

TRYTON(N=146)

Provisional(N=143)

Vessel LocationLAD 75.2% 72.6% 65.0%LCX 21.1% 18.5% 25.9%RCA 3.8% 8.9% 9.1%Lesion LocationOstial 98.5% 96.6% 95.8%Proximal 1.5% 2.7% 2.8%Mid 0.0% 0.0% 0.0%Distal 0.0% 0.7% 1.4%RVD (mm) 2.49±0.20 2.53±0.23 2.52±0.22Lesion Length (mm) 5.94±2.53 4.80±1.24 4.60±0.86Morphologyangulation ≥45o 18.0% 12.3% 24.5%thrombus 0.9% 0.0% 0.0%calcification – mod/severe 9.8% 5.5% 5.6%TIMI Flow (baseline) < 3 8.2% 4.1% 4.2%

TRYTON Confirmatory Study: Acute Angiographic Result

Confirmatory Study Randomized Trial ≥2.25mm

TRYTON (N=133)

TRYTON(N=146)

Provisional(N=143)

Main Vessel (mm)Acute gain In-­stent 1.81±0.47 1.77±0.46 1.78±0.40In-­segment 1.49±0.48 1.38±0.46 1.45±0.44

Side Branch (mm)Acute gainIn-­stent 1.58±0.43 1.53±0.36 naIn-­segment 1.37±0.41* 1.26±0.36 0.59±0.48*

* p<0.001

TRYTON Confirmatory Study: Acute SuccessConfirmatory Study Randomized Trial

≥2.25mm

Acute Success(%) TRYTON(N=133)

TRYTON(N=146)

Provisional(N=143)

Procedure SuccessAchievement of final in-­stent diameter <50% in SB with assigned study device

89.3%*(117/131)

87.4% (125/143)

66.9%*(95/142)

Device SuccessAchievement of final in-­stent residual stenosis <30% (by QCA) in SB using the assigned study device without malfunction

93.8%*(122/130)

94.4%(135/143)

35.9%*(51/142)

Lesion SuccessAchievement of final in-­stent diameter of <50% (by QCA) within the side branch

100%*(133/133)

100% (141/141)

84.5%*(120/142)

* p<0.001

TRYTON Confirmatory Study: Resources Utilization

Confirmatory Study Randomized Trial ≥2.25mm

TRYTON (N=133)

TRYTON(N=146)

Provisional(N=143)

Procedure Time (min) 64.6±26.2 68.7±30.7 55.9±27.3Fluoroscopy Time (min) 23.3±11.4* 24.0±13.8 11.6±5.4Contrast Used (ml) 248.2±85.6 269.2±98.3 227±88.7

*p <0.001

~10 min more and ~30 ml more contrast

NORDIC IV 2 stents(n=229)

92.6 min

22.8 min

238 ml

TRYTON Confirmatory Study: Additional Stents (Site Reported)

2.2% (3/133)1.5% (2/133)

Dissection: 2Lesion Coverage: 0 Dissection: 1

Lesion Coverage: 2

Dissection: 1Lesion Coverage: 3

TRYTON Confirmatory Study: Peri-­Procedural MI 3x ULN CK-­MB

16/143 14/133

%

Performance Goal: 17.9%

Primary Endpoint Met

Error bars represent 1-­sided 95% CI

Pivotal Provisional ≥2.25mm

Confirmatory Study

11.2% 10.5%

16/143 14/133

TRYTON Confirmatory Study: Peri-­Procedural MI 5x ULN CKMB

Pivotal Provisional ≥2.25mm

Confirmatory Study

6.8%5.4%

7/103 7/130

%

TRYTON Confirmatory Study: Procedural and 30-­day Follow-­up

Confirmatory Study Randomized Trial ≥2.25mm

Endpoints (%) TRYTON(N=133)

TRYTON(N=146)

Provisional(N=143)

DeathProcedural 0% (0) 0% (0) 0% (0)30 day 0% (0) 0% (0) 0% (0)

Myocardial Infarction

Procedural (3x CKMB) 10.5% (14/133) 9.2% (13/141) 12.1% (17/141)

Procedural (5x CKMB) 4.5% (7/133) 3.4% (4/118) 6.8% (7/103)

30 day 10.8% (14/130)* 8.2% (12/146) 11.9% (17/143)*

Stent Thrombosis 0% (0) 0.7% (1/146) 0.0% (0/143)

* 2 patients in Confirmatory study have not completed 30 day follow-­up at datalock and 1 patient withdrew at 30 days

TRYTON Confirmatory Study Conclusions

• The TRYTON Confirmatory Study, assessing the safety of the TRYTON stent in the treatment of bifurcation involving large side branches, met its primary endpoint (performance goal) related to peri-­procedural MI

• This finding confirms the safety and efficacy of the TRYTON dedicated bifurcation stent in the treatment of bifurcation involving large sides branches

TRYTON Confirmatory Study Conclusions

• In light of the higher procedural success rate, improved acute angiographic result, and higher rate of side branch patency at 9-­month follow-­up compared to provisional stenting, the TRYTON Confirmatory Study and the TRYTON IDE trial support the use of the dedicated bifurcation TRYTON stent in conjunction with standard DES in the treatment of bifurcation lesions involving large side branches

Tryton-­The Vision : To treat Bifurcation Lesions with the Same Ease, Confidence & Efficacy as Straight Lesions

Thank You