Where to after ILUMIEN III

and DOCTORS?

Ziad A Ali MD DPhilColumbia University Medical Center

Cardiovascular Research Foundation

Disclosure Statement of Financial Interest

• Grant/Research Support

• Consulting Fees/Honoraria

• NIH/NHLBI, St Jude Medical (now Abbott), Cardiovascular Systems Inc

• St Jude Medical, Acist, Cardiovascular Systems Inc, Boston Scientific

Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

• Equity • Shockwave Medical

The ILUMIEN Series of Trials

CLI-OPCI: OCT improves outcomes

vs. angiography

OPUS-Class StudyReliability of OCT measurement

vs. IVUS and angiography

OCT Safety and EfficacyNonocclusive OCT study

Past

Present–2015

Future

OCTOBEROCT optimized bifurcation event

reduction

ILUMIEN IVRandomized controlled outcomes

Other areas under

consideration:

Bifurcation

BVS

PVD

ILUMIEN I:OCT stent guidance parameters

and impact on decision making.

ILUMIEN IIOCT vs. IVUS comparison of

stent expansion

ILUMIEN IIIOCT/IVUS Angio prospective

randomized trial

DOCTORSOCT Optimization impact on FFR

OCT Evidence

0

2

6

10

Min

imu

m L

um

en

Are

a (

mm

2)

8%

4

8

*

Phantom FD-OCT IVUS0

1

2

3

Min

imu

m L

um

en

Dia

me

ter

(mm

)

FD-OCT IVUS QCA

9% 5%

* **

OPUS-CLASS (Phantom vs OCT vs IVUS)

Are OCT and IVUS measurements the same?

Kubo et al. iJACC 2013;6(10):1095-1104

CLIO-PCI III Registry

P

ILUMIEN I:Pre-PCI OCT Impact

91%98%

57%

YES

98

%

Change in

strategy

OCTFFR

Pre-PCI OCT impacted on procedure planning in 57% of cases

PRE-PCI n=467

Stent lengthLonger 43%Shorter 25%

Stent diameterLarger 8 %Smaller 31%

ILUMIEN I: Post-PCI OCT Impact

83%

98%

Post

Optimization

OCTFFR

Post-PCI OCT impacted on procedure in 27% of cases, reducing

malapposition from 51% to 19% and edge dissection 16% to 5%

Post-PCI n=467

27%

YES

Variable Core Lab (%) Operator (%)

Dissection 28 3

Malapposition 32 14

Underexpansion 41 8

Dissection+malap

position9 1

Dissection+under

expansion9 1

Malapp + tissue

protrusion11 1

Dissection+malap

p+underexpansion4 0

Thrombus or

tissue protrusion26 1

ILUMIEN I - Pre-PCI OCT Impact

PCI Strategy decision by OCT

guidance

Pre- and /or Post-PCI

Group

Pre /

Post

N Post-

PCI

MLA

mm2

No Pre-PCI Change Based on OCT and

No Optimization post-PCI - -

137 6.1±2.5

Pre-PCI Change Based on OCT and

No Optimization post-PCI+ - 165 5.2±2.1

No Pre-PCI Change Based on OCT and

Optimization post-PCI- + 41 5.3±1.8

Pre-PCI Change Based on OCT and

Optimization post-PCI+ + 65 5.0±2.0

Stents without optimization (-/-) were larger than the optimized (+/+) stents

W Wijns. Eur Heart J. 2015;36(47):3346-55.

ILUMIEN II1°Endpoint: Post-PCI stent expansion

ADAPT-DES418 pts enrolled

Lesions excluded:

586 patients, 586 lesions

Lesions excluded:

ILUMIEN I

No QCA available (n=1043)

STEMI (n=378)

In-stent restenosis (n=191)

No reference available (n=179)

Left main (n=99)

Poor image quality or media issue

(n=77)

Chronic total occlusion (n=75)

Saphenous vein graft (n=66)

Unreliable pullback (n=66)

Not received by core lab (n=12)

Poor quality (n=45)

Not received by core lab (n=12)

BRS (n=5)

Inconsistent data (n=2)

2,179 pts enrolled in IVUS substudy

354 patients, 354 lesions

Randomly chosen 1 lesion per patient

1:1 Propensity matching

286 patients, 286 lesions286 patients, 286 lesions

Overall study population (n=940)

1:1 Propensity matched groups (n=572)

RVD, lesion length, calcification, reference segment availability

ILUMIEN II – Stent Expansion

Maehara et al. JACC Interv 2015;8:1704-14

If Stent Expansion is the same why does OCT

guidance lead to a smaller MLA compared to

angiography?

Visual Estimation Oversizes vs OCT

Reference Segment

Lumen-guided = 2.5mm stent

EEL-guided = 3.0mm stent

2.4 mm RVD by QCA

(mm)

(mm) 5.0 10.0 15.0 20.0 25.0 30.0

0.5

1.0

1.5

2.0

2.5

3.0

NP NP ND NDo

p

d

r

Reference Segment

Lumen-guided = 2.5mm stent

EEL-guided = 3.0mm stent

2.2mm2 gain by EEL-guidance

Reference Segment

Lumen-guided = 2.25mm stent

EEL-guided = 3.25mm stent

4.3 mm2 gain by EEL-guidance

(mm)

(mm) 5.0 10.0 15.0 20.0 25.0 30.0

0.5

1.0

1.5

2.0

2.5

3.0

NP NP ND NDop d

r

2.6 mm RVD by QCA

Visual Estimation Oversizes vs OCT

OCT vs IVUS

Randomized comparison of IVUS vs OCT-guided stenting

Habara et al. Circ Cardiovasc Interv 2012;5:193-201

0Min

imu

m S

ten

t A

rea

(m

m2)

4

8

IVUS OCT

7.1mm2

6.1mm2

OCT IVUS

Stent Sizing by Angiography 0% 37%

Stent Sizing by Lumen 0% 63%

Stent Sizing by Vessel Wall 100% 0%

Stent Deployment Pressure 14.2±3.4 9.8±2.4

Postdilation 86% 60%

Postdilation pressure 16.1±4.7 13.5±3.4

0Me

an

Ste

nt A

rea

(m

m2)

5

10

IVUS OCT

8.7mm2

7.5mm2

n=70

Border Visibility: Reference segment 62.9%, MLA 8.6%

OFDI

(n=54)

IVUS

(n=49)P

Acute procedural

Stent diameter, mm 2.92 ± 0.38 3.00 ± 0.37 0.007

Max. balloon diameter, mm 3.1 ± 0.8 3.3 ± 1.2 0.058

Follow-up OCT (8 months)

Min lumen area, mm2 4.8 (3.3–5.9) 5.0 (4.4–6.2) 0.18

Mean lumen area, mm2 6.3 (4.8–7.4) 6.3 (5.4–7.9) 0.24

Min stent area, mm2 5.4 (3.8–6.0) 5.8 (5.2–7.6) 0.024

Mean stent area, mm2 6.7 (4.9–7.8) 7.2 (6.2–8.7) 0.055

OPINION

Procedural Characteristics and Results

Kubo et al. iJACC 2017;S1936-878X

Why does OCT guidance lead to a smaller MLA

compared to IVUS?

0

2

6

10

Min

imu

m L

um

en

Are

a (

mm

2)

8%

4

8

*

Phantom FD-OCT IVUS0

1

2

3

Min

imu

m L

um

en

Dia

me

ter

(mm

)

FD-OCT IVUS QCA

9% 5%

* **

IVUS oversizes versus OCTAre OCT and IVUS measurements the same?

Kubo et al. iJACC 2013;6(10):1095-1104

OCT IVUS

Habrara et al. Lumen Vessel Wall

OPINION Lumen Vessel Wall

Comparison of OCT vs IVUS Stent Sizing

Proximal Reference: Lumen vs EEL

n=100 Lumen EEL P

Mean Vessel Diameter (mm) 3.14 ± 0.61 4.08 ± 0.66

Distal Reference: Lumen vs EEL

n=100 Lumen EEL P

Mean Vessel Diameter (mm) 2.68 ± 0.53 3.44 ± 0.58

Stent Diameter: Upsize Lumen vs Downsize EEL

n=100 Lumen EEL P

Mean Lumen Diameter (mm) 2.70 ± 0.44 3.33 ± 0.47

Lumen-

GuidedEEL-Guided

LargestMSA/MLA

ILUMIEN I + Angio

Habrara et al. + IVUS

OPINION + IVUS

ILUMIEN III + =

Comparison of OCT vs IVUS vs Angiography

• In all previous studies comparing stent sizing using lumen-guided OCT to

IVUS or angiography, MSA/MLA has been inferior to the comparator.

• In the only study using EEL-based OCT stent sizing, ILUMIEN III, MSA

was non-inferior to IVUS with a trend towards superiority against

angiography

ILUMIEN III: OPTIMIZE PCI

HYPOTHESIS

Using a novel stent sizing protocol,

OCT-guided PCI will be non-inferior

to IVUS-guided PCI and superior to

angiography-guided PCI in achieving

acute post-PCI MSA.

Pre-PCI OCT Angiography

OCT Stent Sizing Guidance,

per study protocol

OCT guided Optimization per

study protocol

Angiography guided PCI, per

“local standard practice”

Angiographic optimization,

per “local standard practice”

Protocol

Post-PCI OCT

Angiography

Pre-PCI IVUS

Randomization to OCT-,

IVUS- or angiography-

guided PCI

Identification of

study lesion

IVUS guided PCI, per

“local standard practice”

IVUS guided optimization, per

“local standard practice”

Procedure

Complete

Post-PCI OCT, blinded

to investigator

Post-PCI OCT, blinded

to investigator

Inclusion

• Single native vessel

• One or more target lesions

• RVD 2.25mm - 3.50mm

• Length < 40mm

Exclusion:

• Left main

• Ostial RCA

• CTO

• Planned bifurcation

• eGFR

OCT Stent Sizing AlgorithmPre-PCI OCT

Can ≥ 180◦ of the EEL be identified at both

proximal and distal reference segments

Reference stent

diameter decided by

OCT measurement of

smallest mean EEL to

EEL diameter at

reference site

Yes

EEL

Reference stent

diameter decided by

OCT automation based

on smallest mean

lumen diameter at

reference site

No

Lumen

Reference stent length decided by

OCT Automation

84% 16%

OCT Stent Optimization Algorithm

Target MSA (in both proximal and distal halves of the stent relative to the closest reference segment)

Stent Implantation

Angiographic success?• 0% diameter stenosis

Target MSA

criteria achieved?

Final OCT imaging

Post-dilationNo

Post-PCI OCT

Post-dilation

Post-PCI OCT

Target MSA

criteria achieved?Post-dilation

• Acceptable, > 90%

• Unacceptable,

ILUMIEN III: Primary Endpoint

OCT 5.79 mm2 [4.54, 7.34]

IVUS 5.89 mm2 [4.67, 7.80]

0.0 -1.0mm2

-0.70

IVUS betterOCT better NI margin

97.5% one-sided CI: [-0.70, - ]

Pnoninferiority = 0.001

Psuperiority = 0.12

Final post-PCI MSA by OCT

Ali et al. Lancet 2016;2618-28

EndpointsOCT

(n=140)

IVUS

(n=135)

Angio

(n=140)

POCT vs

IVUS

P OCT vs

Angio

Minimal stent area, mm25.79

[4.54,7.34]

5.89

[4.67,7.80]

5.49

[4.39, 6.59]0.42 0.12

Min stent expansion, % 88 ± 17 87 ± 16 83 ± 13 0.77 0.02

Mean stent expansion, %106

[98, 120]

106

[97, 117]

101

[92, 110]0.63 0.001

Optimal Expansion >95% 26% 25% 17% 0.84 0.07

Acceptable 90 -

Lumen-

GuidedEEL-Guided

LargestMSA/MLA

ILUMIEN I + Angio

Habrara et al. + IVUS

OPINION + IVUS

ILUMIEN III + =

Comparison of OCT vs IVUS vs Angiography

• In all previous studies comparing stent sizing using lumen-guided OCT to

IVUS or angiography, MSA/MLA has been inferior to the comparator.

• In the only study using EEL-based OCT stent sizing, ILUMIEN III, MSA

was non-inferior to IVUS with a trend towards superiority against

angiography

Procedural Safety Endpoints

No patient developed acute renal failure

OCT

(n=158)

IVUS

(n=146)

Angio

(n=146)P

OCT vs IVUS

P OCT vs Angio

Procedural MACE 2.5% 0.7% 0.7% 0.37 0.37

Complications

Dissection 1.3% 0.0% 0.7% 0.50 1.00

Perforation 0.0% 0.7% 0.0% 0.48 -

Thrombus 1.3% 0% 0.0% 0.50 0.50

Acute closure 0.6% 0.0% 0.0% 1.00 1.00

Intervention

Additional stent 2.5% 0.7% 0.7% 0.37 0.37

But……

ILUMIEN III Algorithm Compliance

148 patients

IVUS-guided PCI

18 excluded

5 unable to pass catheter

7 uninterpretable image

6 no final OCT done

140 patients with final OCT

Followed OCT Protocol

Yes No

65 patients(46.4%)

75 patients(53.6%)

450 randomized patients

158 patients

OCT-guided PCI148 patients

Angiography-guided PCI

Uncomplicated Patients & Lesions

Number at risk:

146 141 141 141 53Angiography

146 137 135 133 59IVUS

158 152 152 150 59OCT

P=0.33

1.4%

4.3%

2.6%

0

2

4

6

8

0 3 6 9 12

Angiography

IVUS

OCTT

LF

(%

)

Time Post Procedure (Months)

1-Year Target Lesion Failure

Cardiac Death, TV-MI, or ID-TLR

DOCTORS

Meneveaux et al. Circulation 2016;134

DOCTORS – Endpoints

But……..

Which Patients Benefit from Imaging Guidance?

46 year old with HTN, HL and CCS II stable angina

Direct Stent 4.0x15mm EES

Which Patients Benefit from Imaging Guidance?

High Risk Clinical and Lesion Characteristics

1-Year TVF in 2nd Gen DES(cardiac death, TV-MI, or ID-TVR)

ILUMIEN IV

RR [95% CI] P

Diabetes* 1.50 [1.28, 1.76]

ILUMIEN IV: OPTIMAL PCI

2556-3568 pts with high-risk clinical or angiographic features undergoing PCI at 125 centers in the US,

Canada, Western Europe, and Asia-Pacific

Follow-up: Minimum 1 year, maximum 2 yearsPrimary endpoints:

1) Minimal stent area (MSA) by OCT (powered for superiority)2) Target vessel failure (event-driven, powered for superiority)

Principal Investigators: Ziad Ali and Ulf LandmesserStudy Chair: Gregg W. Stone

HR clinical:DiabetesHR angio:

Troponin+ ACS culpritStent length ≥28 mm

2-stent bifurcationSevere calcification

CTODiffuse/MF ISR

Randomize 1:1

OCT-guided* PCI(modified ILUMIEN III protocol)

Angiography-guided PCI

Final OCT (blinded in angiography arm)

Sponsor: Abbott

Stent Diameter

Can the EEL be identified at the distal reference

segment to allow vessel diameter measurement?

Reference stent diameter

decided by OCT

measurement of smallest

mean EEL to EEL

diameter at reference site

rounded down to nearest

stent size

Yes

EEL

Reference stent diameter

decided by OCT

automation based on

smallest mean lumen

diameter at reference site

rounded up to nearest

stent size

No

Lumen

Pre-PCI OCT

Reference stent length decided by

OCT Automation

71% 29%

EEL

Final OCT

imaging

Stent Implantation using angiographic

co-registration

Angiographic

success

(≤0% visual

diameter stenosis)?

No

Post-PCI

OCT

Post-dilation with NC balloon at ≥ 18

atm sized to the reference EEL of one

or both segments (proximal or distal) of

the stent with OCT-assessed

underexpansion, rounded down to the

nearest balloon diameter based on the

post-PCI OCT

No MSA ≥ 90% in the proximal segment of

the stent relative to the proximal

reference and distal segment of the

stent relative to the distal reference?

Post-dilation with NC balloon at ≥ 18

atm sized to the reference EEL of one

or both segments (proximal or distal) of

the stent with angiographic

underexpansion, rounded down to the

nearest balloon diameter based on the

pre-PCI OCT

Do both the proximal and distal reference

segment lumens (within 5mm of the stent

edge) each have a MLA of ≥4.5mm2 ?

NoPlace an additional DES to treat the

reference segment disease, unless

anatomically prohibitive (e.g. diffuse

disease or very small vessel)

Yes, or maximal balloon

and pressure used based

on the pre-PCI OCT

Yes, or maximal balloon and

pressure used based on the post-

PCI OCT

Stent Optimization

Work in progress…..

3.20mm3.49mm

3.54mm

Site Analysis Core Lab Analysis

Mean diameter: 3.52mmStent size: 3.00mm

IEL

EEL

Media

Intima

Adventitia