ILUMIEN III: OPTIMIZE PCI A Randomized Controlled Trial ... · α 0.05, Δ 0.8 mm2, SD 2.3 mm, SD 2.3 mm2,, 140 patients/group = 140 patients/group = 80% power80% power 3. Superiority

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


Distal half

Distal ReferenceDistal MSA


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



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=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=146)(n=146)AngioAngio (n=146)(n=146)



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=135)(n=135)AngioAngio (n=140)(n=140)



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


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)



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






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




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






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




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






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=146)(n=146)AngioAngio (n=146)(n=146)



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

ILUMIEN III: OPTIMIZE PCI A Randomized Controlled Trial ... · α 0.05, Δ 0.8 mm2, SD 2.3 mm, SD 2.3 mm2,, 140 patients/group = 140 patients/group = 80% power80% power 3. Superiority

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