ILUMIEN III: OPTIMIZE PCIILUMIEN III: OPTIMIZE PCIA Randomized Controlled Trial A Randomized Controlled Trial
Comparing OCT-Guided, IVUS-Guided Comparing OCT-Guided, IVUS-Guided and Angiography-Guided PCIand Angiography-Guided PCI
Ziad A Ali, MD, DPhilZiad A Ali, MD, DPhilColumbia University Medical CenterColumbia University Medical CenterNew-York Presybyterian HospitalNew-York Presybyterian Hospital
Cardiovascular Research FoundationCardiovascular Research Foundation
Disclosure Statement of Financial InterestDisclosure Statement of Financial Interest
•• Grant/Research Grant/Research SupportSupport
•• Consulting Fees/Consulting Fees/HonorariaHonoraria
•• NIH/NHLBI, NIH/NHLBI, St Jude Medical, St Jude Medical, Cardiovascular Systems IncCardiovascular Systems Inc
•• St Jude Medical, Acist, Astra Zeneca, St Jude Medical, Acist, Astra Zeneca, Canon, Cardiovascular Systems IncCanon, Cardiovascular Systems Inc
Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
•• EquityEquity •• Shockwave Medical, VitaBx Inc.Shockwave Medical, VitaBx Inc.
ILUMIEN III:OPTIMIZE PCI study was funded by St Jude ILUMIEN III:OPTIMIZE PCI study was funded by St Jude Medical Medical
BackgroundBackground
•• PCI is most commonly guided by PCI is most commonly guided by angiography alone.angiography alone.
• IVUS-guidance has been shown to reduce major adverse cardiovascular events (MACE) after PCI.
•• OCT provides superior OCT provides superior resolution to resolution to IVUS, but data IVUS, but data supporting improved supporting improved or or equivalent equivalent outcomes outcomes are lacking.are lacking.
ILUMIEN III: OPTIMIZE PCIILUMIEN III: OPTIMIZE PCIHYPOTHESISHYPOTHESIS
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”
ProtocolProtocol
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 <30ml/min
OCT Stent Sizing AlgorithmOCT 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
OCT Stent Optimization AlgorithmOCT Stent Optimization AlgorithmTarget 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
• Optimal, > 95% • Acceptable, 90 to <95% • Unacceptable, <90%
OCT Stent Sizing AlgorithmOCT Stent Sizing AlgorithmDistal Reference Proximal Reference
Smallest mean EEL = 3.03 mm � 3.0 x 34 mm stent chosen
Proximal MSA
Proximal half
121% Expansion
OCT Stent Optimization AlgorithmOCT Stent Optimization Algorithm
Proximal Reference
Distal MSA Distal Reference8.5% Underexpansion
Proximal halfDistal half
OCT Stent Optimization AlgorithmOCT Stent Optimization Algorithm
Distal half
Distal ReferenceDistal MSA
OCT Stent Optimization AlgorithmOCT Stent Optimization Algorithm
Distal Reference
104% Expansion
NC Post-dilation
Primary EndpointsPrimary EndpointsPrimary Efficacy Primary Efficacy Endpoint (powered)Endpoint (powered)
Post-PCI Post-PCI MSA assessed by OCT in each randomized MSA assessed by OCT in each randomized armarmHHierarchal testingierarchal testing
1. Non-inferiority 1. Non-inferiority of of OCT- to IVUS-guided stentingOCT- to IVUS-guided stenting α 0.025, Δ 1.0 mm α 0.025, Δ 1.0 mm22, SD 2.3 mm, SD 2.3 mm22,, 140 patients/group = 94% power140 patients/group = 94% power
2. Superiority 2. Superiority of of OCT- to angiography-guided stentingOCT- to angiography-guided stenting α 0.05 α 0.05, , Δ 0.8 mmΔ 0.8 mm22, SD 2.3 mm, SD 2.3 mm22,, 140 patients/group = 140 patients/group = 80% power80% power
3. Superiority 3. Superiority of of OCT- to IVUS-guided stentingOCT- to IVUS-guided stenting α α 0.05, Δ 0.05, Δ 0.8 mm0.8 mm22, SD , SD 2.3 mm2.3 mm22,, 140 patients/group = 80% 140 patients/group = 80% powerpower
Primary Safety Endpoint (not powered)Procedural MACE
Procedural complications (angiographic dissection, perforation, thrombus, or acute closure) requiring active intervention (prolonged balloon inflations, additional stent
implantation, or pericardiocentesis)
Screen Failures n =1230Withdrawal of consent n = 1Withdrawn by investigator n = 3Software malfunction n = 1
1759 Patients consented
450 Randomized
158 OCT-guided PCI 146 angiography-guided PCI146 IVUS-guided PCI
74 Roll-in subjects
140 Final OCT available for primary endpoint analysis
140 Final OCT available for primary endpoint analysis
135 Final OCT available for primary endpoint analysis
158 30-day follow-up completed
140 30-day follow=up completed
143 30-day follow=up completed
Randomization and Follow-upRandomization and Follow-up
Study OrganizationStudy Organization• Principal Investigator: Ziad Ali
• Chairman: Gregg Stone
• Academic Research Organization: CRF - Ori-Ben Yehuda (Director)
• Steering Committee: Gregg Stone, Ziad Ali, Habib Samady,
Giulio Guagliumi, Takashi Akasaka
• Intravascular Imaging Core Lab: CRF - Akiko Maehara (Director)
• Angiographic Core Lab: CRF - Philippe Généreux (Director)
• Data Safety Monitoring: Allen Jeremias, Joseph Carozza,
John Ambrose, Michael Parides
• Clinical Endpoints Committee: Ozgen Dogan, David Engel, Chiu Wong
• Site & Data Management and Data Monitoring: St. Jude Medical
• Sponsor: St Jude Medical
Highest EnrollersHighest EnrollersInvestigator Investigator Institution Institution City/State/CountryCity/State/Country NN
Richard Shlofmitz St Francis Hospital Roslyn, NY, USA 65
Franco Fabbiocchi Centro Cardiologico Monzino Milan, Italy 65
Tamim Nazif Columbia University New York, NY, USA 58
Giulio Guagliumi Ospedale Papa Giovani XXIII Bergamo, Italy 65
Perwaiz Meraj Northwell Health Manhasset, NY, USA 27
Fernando Alfonso Hospital Universitario de La Princesa Madrid, Spain 25
Eric Carlson Eastern Cardiology Greenville, NC, USA 19
Massoud Leesar University of Alabama Birmingham, AB, USA 17
Baseline CharacteristicsBaseline CharacteristicsOCTOCT
(n=158)(n=158)IVUS IVUS
(n=146)(n=146)AngioAngio (n=146)(n=146)
AgeAge 66 [59, 72] 66 [61,72] 67 [56, 74]
MaleMale 69% 73% 73%
HypertensionHypertension 79% 77% 75%
DyslipidemiaDyslipidemia 73% 73% 76%
Diabetes mellitusDiabetes mellitus 33% 38% 29%
Current smokerCurrent smoker 18% 13% 24%
Serum creatinine, mg/dl 0.90
[0.80, 1.03]0.91
[0.80, 1.10]0.90
[0.79, 1.10]
Silent ischemia/staged Silent ischemia/staged 34% 27% 28%
Stable anginaStable angina 34% 34% 34%
Acute coronary syndrome Acute coronary syndrome 34% 36% 35%
Angiographic CharacteristicsAngiographic CharacteristicsOCTOCT
(n=158)(n=158)IVUS IVUS
(n=146)(n=146)AngioAngio (n=146)(n=146)
PPOCT vs OCT vs IVUSIVUS
P P OCT vs OCT vs AngioAngio
LAD/LCx/RCA 51/27/22% 47/29/25% 57/21/22% NS NS
Thrombus 1.3% 1.4% 1.4% 1.00 1.00
Calcification (mod to severe) 20% 16% 26% 0.39 0.23
Reference vessel diameter, mm 2.78 [2.42, 3.12]
2.87 [2.56, 3.17]
2.76 [2.50, 3.15] 0.34 0.97
Minimum lumen diameter, mm 0.99 [0.70, 1.24]
1.03 [0.73, 1.26]
0.95 [0.68, 1.21] 0.83 0.49
Diameter stenosis, % 64.1 [55.8, 73.1]
63.7 [56.0, 73.0]
66.0 [57.8, 74.9] 0.99 0.35
Lesion length, mm 15.5 [11.0, 23.2]
15.3 [11.0, 23.0]
14.8 [10.6, 20.4] 0.99 0.40
TIMI III flow 91% 90% 88% 0.68 0.41
Procedural CharacteristicsProcedural CharacteristicsOCTOCT
(n=158)(n=158)IVUS IVUS
(n=146)(n=146)AngioAngio (n=146)(n=146)
PPOCT vs OCT vs IVUSIVUS
P P OCT vs OCT vs AngioAngio
Radial Access 66% 60% 62% 0.26 0.50
Stents per lesion 1 [1, 1] 1 [1, 1] 1 [1, 1] 0.58 0.93
Stent length, mm 23 [15, 32] 24 [16, 32] 20 [16, 30] 1.00 0.27
Maximal stent diameter, mm 3.00 [2.75, 3.50]
3.00 [2.75, 3.50]
3.00 [2.75, 3.50] 0.36 0.39
Post-dilatation balloons used, n 2 [1, 3] 2 [1, 3] 1 [1, 2] 0.80 0.0005
Maximum balloon size, mm 3.5 [3.0, 4.0] 3.5 [3.0, 4.0] 3.0 [3.0, 3.5] 0.94 0.0007
Maximum inflation pressure, atm 18 [16, 20] 20 [16, 20] 18 [16, 20] 0.48 0.02
Procedure duration, min 71 [57,101] 73 [54,97] 58 [39,78] 0.99 <0.0001
Radiation dose, Gy 1.3 [0.85, 2.0] 1.2 [0.74, 2.3] 1.2 [0.70, 2.0] 0.87 0.39
Contrast volume, mL 222 [164, 285] 190 [140, 250] 183 [140, 250] 0.004 0.001
Border and Vessel VisibilityBorder and Vessel VisibilityOCTOCT
(n=140)(n=140)IVUSIVUS
(n=135)(n=135)PP
OCT vs OCT vs IVUSIVUS
EEL visible at either reference segment
>180°
Site 84% 83% 0.78
Core lab 95% 100% 0.02
Measurement used to decide stent sizing
Proximal reference
EEL 70% 71% 0.89
Lumen 30% 29%
DIstal reference
EEL 79% 70% 0.09
Lumen 21% 30%
Primary EndpointPrimary Endpoint
OCT 5.79 mmOCT 5.79 mm22 [ [4.54, 7.344.54, 7.34]]IVUS 5.89 mmIVUS 5.89 mm2 2 [4.67, 7.80] [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
Angiography Angiography 5.49mm5.49mm2 2 [4.39, 6.59] [4.39, 6.59]Psuperiority = 0.12
Final post-PCI MSA by OCT
Secondary EndpointsSecondary EndpointsOCTOCT
(n=140)(n=140)IVUS IVUS
(n=135)(n=135)AngioAngio (n=140)(n=140)
PPOCT vs OCT vs IVUSIVUS
P P OCT vs OCT vs AngioAngio
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
Expansion
- Optimal (>95%) 26% 25% 17% 0.84 0.07
- Acceptable (90 - <95%) 16% 12% 3.7% 0.42 0.0008
- Unacceptable (<90%) 59% 63% 79% 0.45 0.0002
DissectionsDissections
Major Dissection1) Angle >60°
3mm
2) Length >3 mm
OCTOCT(n=140)(n=140)
IVUS IVUS (n=135)(n=135)
AngioAngio (n=140)(n=140)
PPOCT vs IVUSOCT vs IVUS
P P OCT vs OCT vs AngioAngio
Dissection, any 28% 40% 44% 0.04 0.006 Major 14% 26% 19% 0.009 0.25 Minor 14% 13% 25% 0.84 0.02
Angle Length
Dissection Detection in the IVUS arm: Dissection Detection in the IVUS arm: OCT vs. IVUSOCT vs. IVUS
1mm
IVUSIVUS(n=140)(n=140)
OCTOCT(n=135)(n=135)
PPOCT vs IVUSOCT vs IVUS
Dissection, any 16% 40% <0.0001
Major 11% 26% <0.0001
Minor 5.1% 13% 0.03
MalappositionMalapposition
Lumen Area; 5.47mm2
Stent Area; 4.32mm21mm
MajorStrut(s) >0.2 mm from vessel edge
and stent underexpansion
OCTOCT(n=140)(n=140)
IVUS IVUS (n=135)(n=135)
AngioAngio (n=140)(n=140)
PPOCT vs IVUSOCT vs IVUS
P P OCT vs OCT vs AngioAngio
Malapposition, any 41% 38% 59% 0.62 0.002
Major 11% 21% 31% 0.02 <0.0001
Minor 31% 18% 28% 0.01 0.60
Strut
1mm
Malapposition Detection in the IVUS arm: Malapposition Detection in the IVUS arm: OCT vs. IVUSOCT vs. IVUS
IVUSIVUS(n=140)(n=140)
OCTOCT(n=135)(n=135)
PPOCT vs IVUSOCT vs IVUS
Malapposition, any 19% 39% 0.0002 Major 14% 21% 0.06 Minor 5.0% 18% 0.003
Malapposition
Plaque/Thrombus ProtrusionPlaque/Thrombus Protrusion
Mass >0.2 mm from vessel edge and protrusion area/stent area
≥10%
Protrusion Area/Stent Area ≥ 10%1mm
OCTOCT(n=140)(n=140)
IVUS IVUS (n=135)(n=135)
AngioAngio (n=140)(n=140)
PPOCT vs IVUSOCT vs IVUS
P P OCT vs OCT vs AngioAngio
Protrusion, any 67% 74% 68% 0.21 0.90
Major 19% 20% 17% 0.88 0.76
Minor 48% 54% 50% 0.30 0.72
Major
Tissue protrusion
1mm
Plaque/Thrombus Plaque/Thrombus Protrusion Detection Protrusion Detection in the IVUS arm: OCT vs. IVUSin the IVUS arm: OCT vs. IVUS
IVUSIVUS(n=140)(n=140)
OCTOCT(n=135)(n=135)
PPOCT vs IVUSOCT vs IVUS
Protrusion, any 20% 74% <0.0001 Major 7.1% 20% 0.0004 Minor 12% 54% <0.0001
Tissue protrusion Tissue protrusion
Procedural Safety EndpointsProcedural Safety Endpoints
No patient developed acute renal failure
OCTOCT(n=158)(n=158)
IVUS IVUS (n=146)(n=146)
AngioAngio (n=146)(n=146)
PPOCT vs IVUSOCT vs IVUS
P P OCT vs OCT vs AngioAngio
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
30-day Clinical Outcomes30-day Clinical OutcomesOCTOCT
(n=158)(n=158)IVUS IVUS
(n=146)(n=146)AngioAngio (n=146)(n=146)
PPOCT vs OCT vs IVUSIVUS
P P OCT vs OCT vs AngioAngio
MACE 2.5% 1.4% 0.7% 0.69 0.38
Death 0.0% 0.0% 0.0% - -
Myocardial Infarction 1.3% 0.7% 0.0% 1.00 0.50
Ischemia-driven TLR 0.6% 0.0% 0.7% 1.00 1.00
Any revascularization 1.9% 0.7% 0.7% 0.62 0.63
Stent thrombosis 0.6% 0.0% 0.0% 1.00 1.00
LimitationsLimitations
•• SSpecific pecific IVUS-guided IVUS-guided and angiography-and angiography-guided stent strategies were not mandated. guided stent strategies were not mandated.
•• Bioresorbable Bioresorbable scaffolds were not scaffolds were not included.included.
•• Masking investigators Masking investigators and patients was and patients was not not feasible.feasible.
•• Trial was not powered for clinical Trial was not powered for clinical outcomes.outcomes.
ConclusionsConclusions•• OCT-guided PCI using a specific EEL-based OCT-guided PCI using a specific EEL-based stent optimization strategy was non-inferior stent optimization strategy was non-inferior to IVUS-guided PCI for achieving MSA.to IVUS-guided PCI for achieving MSA.
• OCT-guided PCI resulted in superior stent expansion and procedural success compared to angiography-guided PCI.
•• OCT-guided PCI resulted in the fewest OCT-guided PCI resulted in the fewest untreated major dissections and areas of untreated major dissections and areas of major stent malapposition.major stent malapposition.
ConclusionsConclusions
•• The efficacy of OCT-guided PCI with The efficacy of OCT-guided PCI with the ILUMIEN III stent optimization the ILUMIEN III stent optimization protocol to improve event-free survival protocol to improve event-free survival after DES will be evaluated in the after DES will be evaluated in the upcoming large-scale, randomized upcoming large-scale, randomized pivotal ILUMIEN IV trial.pivotal ILUMIEN IV trial.
Dedicated to you Parisa, the greatest thing that ever happened to me. I love you with every cell in my body,
Daddy
Simultaneous Simultaneous PublicationPublication
The LancetThe Lancet