Update and current status on PROSPECT II/PROSPECT...

Update and current status on

PROSPECT II/PROSPECT ABSORB

Optics in Cardiology

Zurich 2018

Prof David ErlingeDept of Cardiology

Lund University

Lund, Sweden

Non-Flow Limiting Vulnerable Plaque

• A plaque that is non-flow limiting, but will cause a

coronary event.

• FFR/iFR can by definition not detect Non-flow

limiting plaques.

• We need other methods to detect these plaques

Lipid in PlaqueThin Cap Fibroatheroma

with rupture (70%)

Lipid core in all

Erosion (no obvious rupture (30%)

Lipid pool in both (about 50% have lipid pool (M Joner

personal communication)

Calcified nodule (2-5%). No lipid.

Approximately 85% of plaques causing

sudden death have lipid core or lipid pool

Falk et al., EHJ 2013

Lund-Stockholm outcome study

Improvements

• Both 20 and 50 MHz ultrasound giving

“OCT-like” resolution combined with

depth

• 4 x faster pullback

• Thin cap detection with collagen

algorithm

NIRS technology: Intravascular Diffuse Reflectance

5

Vessel Wall

SpecularReflections

Diffuse Reflectance

detected

NIRS Light

Uncollected light

• The returned near infrared light along with knowledge of the delivered light allow computation of absorption spectra

• Absorption spectra can be used to identify molecules

Absorbance Spectra

NIRS generated Chemogram

maxLCBI4mm: 0-1000

Erlinge, (review) J Internal Medicine 2015

NIRS-IVUS in pathology specimens

(NIRS)-IVUS detects plaque volume• Intravascular ultrasound

(IVUS) can see External

Elastic Lamina (EEL) and

Lumen.

• EELarea-Lumenarea/EELarea=

Plaque Burden PB/Percent

Atheroma Volume (PAV)

Plaque

burden/

volumeLumen

Lumen

EEL

McPherson JA et al. JACC Img 2012;5:S76–85; Stone, GW et al., NEJM, 2011.

The prospective importance of plaque burden has been confirmed in the

PREDICTION and VIVA trials: Stone,P Circ 2012, Calvert JACC CVI 2011

Me

dia

n 3

.4 y

r M

AC

E r

ate

pe

r le

sio

n (

%)

0,0%0,6% 0,5%

2,5%

9,5%

0%

2%

4%

6%

8%

10%

12%

<40% 40% - 50%(n=904)

50% - 60%(n=1,239)

60% - 70%(n=798)

≥70% (n=298)

Plaque burden

thousands

PROSPECT: Correlates of Non-culprit Lesion

Related Events: Impact of plaque burden

31% of pts having at least one non-culprit

lesions with PB≥70%

But only 28 of these 298 >70% plaques

caused a coronary event

NNT = 11

Plaque

burden

>70%

Lumen

Lipid rich plaques defined by NIRS cause STEMI

Typical circular lipid-rich plaque with MaxLCBI4mm of 920 in LAD in a

patient with an inferior STEMI. Erlinge, (review) J Internal Medicine 2015

Core lab confirmation of a NIRS

treshold for STEMI plaques

Confirmation that MaxLCBI4mm >400 is detected in the majority of STEMI culprit

plaques

Madder…Erlinge, ATVB 2016

A cut-off of maxLCBI >400 had high sensitivity and specificity to detect a culprit

NSTEMI plaque

NSTEMI and Unstable angina culprit plaques have

more lipid as detected with NIRS

Madder…Erlinge, Catheterization Cardiovascular Interventions, 2014

NIRS and Plaque Burden

Khan… Madder, abstract TCT 2015

Rarity of Non-culprit PB70 Lesions with Concurrent Large Lipid BurdenWhereas PB70 lesions accounted for 12.0% of all non-culprit plaques, PB70 lesions with a concurrent

maxLCBI4mm ≥400 are rare, accounting for only 2.1% of all non-culprit lesions.

NIRS added to Plaque Burden

Khan… Madder, abstract TCT 2015

Two Lesions Having a Large Plaque BurdenThis figure highlights the ability of combined NIRS-IVUS imaging to

differentiate lesions having a large PB into those with (left) and without (right)

substantial lipid content.

Post-thrombectomy

LCBI: 604

LCBI: 466

Thrombus and Lipid-rich Aspirate

Reduced lipidcore in NIRS.

Pre-thrombectomy

In vivo histological validation of NIRS detecting lipid

rich plaque

Erlinge et al, EHJ CV imaging 2014

Pre-thrombectomy Post-Thrombectomy0

200

400

600

800

LCBI

p = 0.0001

Pre-thrombectomy Post-Thrombectomy0

200

400

600

800

1000

maxLCBI 4mm

p = 0.001

Thrombectomy is Coronary Liposuction

Erlinge et al, EHJ CV imaging 2014

NIRS in non-culprit plaquespredicts clinical

outcomes• Pooled Atheroremo-NIRS and

IBIS-3 – Serruys

• Large single-center registry with extended FU – Madder

• ORACLE-NIRS – Brilakis

• Sweden-NIRS - Erlinge

Schuurman et al., EHJ 2017

Danek et al., CV Revasc Med 2017

Karlsson…Erlinge, submitted

• LCBI and maxLCBI in non-culprit segments strongly predicts MACE

Madder et al, EHJ CVI 2016

Prospective Identification by NIRS of a Lipid-

Rich Plaque that Caused a Myocardial Infarction

Site of Index

MI –was stented

Possible Vulnerable

Plaque in LAD

4 Months

New MI

New culprit

lesion

at lipid-rich site.

• High lipid in D1 (first culprit) and in prox LAD.

• maxLCBI4mm: 722 in D1, 573 in LAD

NIRS: Lipid rich, collagen low plaque predicted NSTEMI and

ruptured plaque

Lipid detection algorithm (yellow)

Collagen detection algorithm (red)

(only measured in lipidrich areas)

LAD ruptured plaque 4 months later

White areas indicating thin cap (low collagen) in LAD plaque

PROSPECT II Study900 pts with ACS at 16 hospitals

NSTEMI or STEMI >12h

IVUS + NIRS (blinded) pre-PCI in culprit vessel(s)

Successful PCI of all intended lesions (by angio ± FFR/iFR)

Formally enrolled

IVUS + NIRS (blinded) (prox 6-10 cm of each coronary artery)

3-vessel imaging post PCI

Angiography to core lab: Adjudication to non-culprit or culprit lesion.

IVUS + NIRS if possible

Coronary Event

PI: David Erlinge

Chairman: Gregg Stone

Enrollment complete dec 2017: 902 patients

• Primary endpoint: Patient level non-culprit lesion-related major adverse

cardiac events (NC-MACE) through 2 years: cardiac death, MI, unstable

angina/progressive angina requiring repeat hospitalization or symptom-

driven revascularization by CABG or PCI, adjudicated to an originally

untreated non-culprit lesion.

PROSPECT II (Natural History Study):

PRIMARY ENDPOINT

PROSPECT II Study

PROSPECT ABSORB RCT

900 pts with ACS after successful PCI3 vessel IVUS + NIRS (blinded)

≥1 IVUS non-flow limiting lesion with ≥70% plaque burden?

Routine angio/3V IVUS-NIRS FU at 2 years

Yes(N=182)

No(n=720)

ABSORB BVS

+ GDMT (N~100)

GDMT(N~100)

R

1:1

Clinical FU for ≥2 years (up to 15 years in registers)

PROSPECT ABSORB, The ABSORB BVS

Neo-media vascular

smooth muscle cells

Cap sealing

PROSPECT ABSORB

PRIMARY ENDPOINT

• The minimal luminal area (MLA) at the randomized

non-culprit lesion site in patients treated with the

ABSORB BVS + GDMT compared to GDMT only

measured at 25 months (superiority)

• Death, TV-MI, TLR (noninferiority, not powered)

MLAMLA

2 years

”Plaque Sealing”

Follow up in P2/PA• 95% 2y follow up in PROSPECT2

• 87% angiographic follow up at 25 month in PROSPECT ABSORB

ABSORB II: 3 year data

• Depressing results

Serruys et al, Lancet 2016

SAFETY PROSPECT ABSORB

• In PROSPECT ABSORB we have not seen any definite stent thrombosis

• Some minor complications: Occluded side branch, distal dissection, one restenosis upon reexamination.

• Most PROSPECT ABSORB patients in Lund look great at reexamination

• DSMB (Serruys, Koenig, Tijssen and Wykrzykowska) recommended the study to continue at the last DSMB meeting. However, they recommended PSP technique and DAPT for 2 years.

• 25 months follow up completed dec 2019