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