Updated Results and Implications of the Lipid Rich Plaque Study Ron - - PowerPoint PPT Presentation

Updated Results and Implications

• f the Lipid Rich Plaque Study

Ron Waksman, MD, FACC, FSCAI,FESC

Professor of Medicine Georgetown University Associate Director of Cardiology Director of Cardiovascular Research and Education MedStar Washington Hospital Center

Disclosures

• Advisory boards: Abbott Vascular, Amgen, Boston Scientific, Medtronic,

Philips Volcano, Pi-Cardia LTD, and Cardioset

• Consultant: Abbott Vascular, Amgen,, Biotronik, Boston Scientific,

Medtronic, Philips Volcano

• Grant support: Abbott Vascular, AstraZeneca, Biotronik, Boston

Scientific, and Chiesi

• Speaker bureau: AstraZeneca
• Equity: MedAlliance, DOMed, Pi-Cardia LTD, Cardioset

Clinical Unmet Need

• Despite optimal medical therapy and risk modifications strategies,

coronary events continue to occur, in contrast Many individuals with an apparently adverse risk factor profile remain asymptomatic

• The quest for detecting patients at risk for secondary cardiovascular

event (cardiac death, and MI) is a high priority

• Lipid Rich Plaque is associated with ACS & MI and can be detected by

Near Infrared Spectroscopy (NIRS)

• The LRP study is the largest study ever to examine whether NIRS

imaging can identify Vulnerable Patients and Vulnerable Plaques

• during a 24-month period?

Intravascular Imaging System & Catheter

• Combines IVUS and NIRS in single

imaging system

• Cleared in the USA, Europe, Japan,

and Korea

• Only technology labeled for the

detection of Lipid Core Plaques and detection vulnerable plaques and patients

• 3.2Fr crossing profile
• 0.014” wire compatible
• 6Fr guide catheter compatible

IVUS + NIRS Imaging

NIRS Imaging

Chemogram display

• Identifies locations of lipid core plaque in the artery



No Lipid-Rich Plaque (RED)



Lipid-Rich Plaque (YELLOW) Lipid Core Burden Index (LCBI)

• Quantitative summary metric of Lipid Core in a

scanned or selected region

• LCBI scale is from 0 to 1000



LCBI = (Yellow pixels) x 1000

(Total valid pixels)

• maxLCBI4mm: The maximum 4mm LCBI value in a

scanned or selected region



Proxy for angular extent of lipid core plaque

maxLCBI4mm: 824 Selected Region LCBI: 228

The Lipid-Rich Plaque Study

Ron Waksman, MD on behalf of the LRP Investigators MedStar Washington Hospital Cen

Presented as LBT at TCT 2018

FDA expansion of labeling April 2019

September 27, 2019

Simultaneous Publication in the Lancet

LRP Study Endpoints

Co-primary Endpoints Vulnerable Patient Association between maxLCBI4mm in all imaged arteries and future patient-level non-culprit MACE* Vulnerable Plaque Association between maxLCBI4mm in a segment and incidence of future non-culprit MACE* in same segment Key Secondary Endpoint A threshold of maxLCBI4mm>400 will identify patients and plaques at increased risk of a non-culprit MACE*

• Cardiac death
• Cardiac arrest
• Non-fatal myocardial infarction
• Acute coronary syndrome
• Revascularization by CABG or PCI
• Rehospitalization for progressive angina with

>20% stenosis progression

*Non-culprit MACE (independently adjudicated by CEC blinded to NIRS)

Study Flow Diagram

Enrolled patients n = 1563

Patients with no analyzable vessels n = 11

Pts with evaluable LCBI4mm n = 1552

maxLCBI4mm < 250 Randomly assigned 1:1 to follow up

Patients = 1271 Ware segments = 5755 Ware segment IVUS = 5743 Screened patients n = 5273

Screen Failures: Diagnostic only, no PCI (1356) Angiographic exclusion criteria (1045) No IVUS clinically required (707) Physician discretion (452) Technical issues (72) General exclusion criteria (46) Unknown (32)

maxLCBI4mm ≥ 250 All followed up

Feb 2014 - Mar 2016

Patients randomized to no follow up n = 281

Waksman R, et al. Am Heart J. 2017 Oct;192:98-104.

NCT02033694

Clinical Presentation

2.5% 14.3% 36.8% 46.3% 0% 10% 20% 30% 40% 50% 60% Stabilized STEMI Non-STEMI Unstable Angina Stable Angina

Baseline Medications

Medication Pre-admission Discharge Aspirin 75.5% 94.6% ADP Receptor inhibitor 45.8% 89.8% DAPT 41.3% 86.7% Lipid-lowering agent 74.7% 92.0% Statin Any 73.1% 91.1% Statin Only 68.8% 85.8% Non-statin Any 5.8% 6.2% Non-statin Only 1.6% 0.9% Fibrate 2.0% 2.2% Bile-acid sequestrant 0.6% 0.4%

Overall Cumulative MACE Incidence

8.7% 8.8% 2.3%

Cumulative Incidence Rates of Patient Level Events at 2 Years

2.1%

n=24

0.3%

n=4

4.0%

n=47

3.0%

n=35

0.7%

n=8

4.7%

n=57

1.1%

n=13

0.0% 2.0% 4.0% 6.0% 8.0% 10.0%

Cardiac Death Cardiac Arrest ACS Non-fatal MI Rehosp, Progressive Angina, >20% DS progression PCI CABG

Series 1

NC-MACE

HR [95% CI] p Value Conclusion Primary Endpoint: maxLCBI4mm as a continuous variable 1.18 [1.05-1.32] 0.004 For each 100 unit increase of maxLCBI4mm the risk of NC- MACE increased by 18% Secondary Endpoint: maxLCBI4mm>400 1.89 [1.26-2.83] 0.002 A patient with maxLCBI4mm greater than 400 is at 89% higher risk of NC-MACE

Vulnerable Patient Level Endpoint – Results

Adjusted by age, male gender, diabetes, hypertension, smoking history, prior PCI, ACS, and renal insufficiency

Patient Cumulative NC-MACE Incidence

plogrank<0.001

13% 6%

57 Plaque Level Events by Clinical Event Type

22 10 4 36 10 5 10 15 20 25 30 35 40 45 50 ACS Non-Fatal MI Rehosp, Progressive Angina, >20% DS progression PCI CABG Count

38.6% 17.5% 17.5% 7.0% 63.2%

Ware segment may be associated with multiple event types

HR [95% CI] p Value Conclusion Primary Endpoint: maxLCBI4mm as a continuous variable 1.45 [1.30-1.60] <0.0001 For each 100 unit increase of maxLCBI4mm the risk of NC- MACE increases by 45% Secondary Endpoint: maxLCBI4mm >400 4.22 [2.39-7.45] <0.0001 A coronary segment with maxLCBI4mm greater than 400 is at 322% higher risk of NC-MACE

Vulnerable Plaque Level Endpoint - Results

Patient cluster adjusted via WLW methodology

Plaque Cumulative NC-MACE Incidence

3.2% 0.8%

plogrank<0.001

IVUS Core Laboratory Data Ware Segment Level within maxLCBI4mm

Variable Value (n=5743) Lumen area(mm2) 7.8 ± 4.3 Vessel area(mm2) 13.2 ± 6.8 Vessel volume (mm3) 52.2 ± 27.4 Lumen Volume (mm3) 30.6 ± 17.1 Plaque Volume (mm3) 21.5 ± 14.4 Plaque area (mm2) 5.4 ± 3.6 Plaque Burden (%) 38.9 ± 14.0 MLA (mm2) 6.6 ± 3.7 Plaque burden at the MLA (%) 43.9 ± 15.9

Summation of the total scanned length excluding the stented region and 5mm edges Ware segment analysis restricted to only include segments with an evaluable maxLCBI4mm value

Co-primary endpoint

Vulnerable Plaque Level Multivariable-Adjusted Cox Proportional Hazards Models

00

Variable Hazard Ratio [95% CI] maxLCBI4mm continuous maxLCBI4mm > 400

Unadjusted LCBI alone

maxLCBI4mm 1.45 [1.28-1.64] 4.04 [2.28-7.15]

Multivariable-Adjusted Model

maxLCBI4mm >400 3.46 [1.89-6.35] Plaque burden within maxLCBI4mm ≥70%ǂ 3.99 [1.37-11.61] MLA within maxLCBI4mm ≤4mm²§ 1.84 [1.04-3.26]

MaxLCBI4mm= 583

Lumen Area (mm2)

7.26 7.87 7.58 6.28 4.38

Plaque Burden (%)

32.29 29.77 34.88 49.85 62.35

MAR 2016 JUN 2016

MaxLCBI4mm Location

Longitudinal distribution of vulnerable plaque/lipid rich plaque in non-culprit lesions: A Lipid Rich Plaque (LRP) Study Sub-analysis

Evan Shlofmitz, Rebecca Torguson, Paige Craig, Kazuhiro Dan, Corey Shea, Priti Shah, Hector Garcia- Garcia, Ron Waksman MedStar Washington Hospital Center

TCT 2019

“Ware Segment” Distribution

Far Distal RCA 2.3% Prox LCX 15.4% Mid LCX 12.0% Distal LCX 3.7% Prox LAD 16.7% Mid LAD 14.4% Prox RCA 6.9% Mid RCA 7.1% Distal RCA 6.0% LM 1% Distal LAD 12.0% Far Distal LCX 0.3% Far Distal LAD 3.1%

*RCA 22.3% *LAD 46.3% *LCX 31.4% *Prox 39.1%

Professor James Ware

Harvard T.H. Chan School

• f Public Health

HR [95% CI] p Value maxLCBI4mm as a 100 unit continuous variable 1.31 [1.14-1.50] 0.0001 Proximal location 2.60 [1.41-4.79] 0.002 Plaque burden >70% 2.42 [0.77-7.56] 0.13 MLA ≤4 2.46 [1.34-4.53] 0.004

Multivariable Plaque Level NC-MACE Hazard Model

maxLCBI4mm as a continuous variable

Patient cluster adjusted via random effects methodology. Interaction terms between maxLCBI4mm with proximal location, plaque burden >70, and MLA ≤4, respectively, were not significant (p>0.05).

HR [95% CI] p Value maxLCBI4mm >400 2.56 [1.38-4.77] 0.003 Proximal location 3.12 [1.71-5.70] 0.0002 Plaque burden >70% 3.13 [1.03-9.48] 0.04 MLA ≤4 2.56 [1.39-4.72] 0.003

Multivariable Plaque Level NC-MACE Hazard Model

maxLCBI4mm >400

Patient cluster adjusted via random effects methodology. Interaction terms between maxLCBI4mm >400 with proximal location, plaque burden >70, and MLA ≤4, respectively, were not significant (p>0.05).

Conclusions

• In stable and ACS patients who presented to the cath lab for possible PCI and

were treated medically by the guidelines, nearly 9% experienced subsequent non-culprit events within 24 months.

• Multi-vessel NIRS can be easily and safely performed to assess and identify

vulnerable patients and vulnerable plaques.

• Intravascular NIRS imaging in mildly or non-obstructive coronary arteries can

be used as a tool to identify both patients and non-culprit arteries at high risk for future events and should be considered for use in patients undergoing cardiac catheterization with possible PCI.

• Studies for the use of NIRS-guided therapy should be conducted to address

and mitigate the high risk of these patients and arteries.

Clinical Impact

• Patients undergoing NIRS scanning with high LCBI are at higher risk for

subsequent events

• NC Plaques with High LCBI are at higher risk for CV events

What can be done?

• Multi-vessel scanning with NIRS especially in patients with high risk

profile for CV events

• Treat patients with High LCBI with high intensity of statin, PCSK9, anti-

inflammatory agents ETC.

• Treat the NC plaque with best in class DES if the event rate will be

<3.2% at 2 years (Ultimate & Complete studies with low ID-TLR)