PROSPECT
Providing Regional Observations to Study Predictors
of Events in the Coronary Tree
Implications from
PROSPECT and Future
Directions
Gregg W. Stone, MD
Columbia University Medical Center
The Cardiovascular Research Foundation
PROSPECT
• Gregg W. Stone

Scientific Advisory Board for an
honoraria from Abbott Vascular and
Boston Scientific

Research grants from InfraReDx and
Volcano
PROSPECT
700 pts with ACS
UA (with ECGΔ) or NSTEMI or STEMI >24º
undergoing PCI of 1 or 2 major coronary arteries
at up to 40 sites in the U.S. and Europe
Metabolic S.
• Waist circum
• Fast lipids
• Fast glu
• HgbA1C
• Fast insulin
• Creatinine
PCI of culprit lesion(s)
Successful and uncomplicated
Formally enrolled
PI: Gregg W. Stone
Sponsor: Abbott Vascular; Partner: Volcano
Biomarkers
• Hs CRP
• IL-6
• sCD40L
• MPO
• TNFα
• MMP9
• Lp-PLA2
• others
PROSPECT
3-vessel imaging post PCI
Culprit artery, followed by
non-culprit arteries
Angiography (QCA of entire coronary tree)
IVUS
Virtual histology
Palpography (n=~350)
Meds rec
Aspirin
Plavix 1yr
Statin
Repeat biomarkers
@ 30 days, 6 months
Proximal 6-8
cm of each
coronary
artery
MSCT
Substudy
F/U: 1 mo, 6 mo,
1 yr, 2 yr,
±3-5 yrs
N=50-100
Repeat imaging
in pts with events
PROSPECT: MACE (N=697)
All
Culprit lesion (CL) related
Non culprit lesion (NCL) related
Indeterminate
25
MACE (%)
20
20.4%
15
12.9%
10
11.6%
5
2.7%
0
0
1
2
3
506
543
553
604
480
518
521
583
Time in Years
Number at risk
ALL
CL related
NCL related
Indeterminate
697
697
697
697
557
590
595
634
MACE = cardiac death, cardiac arrest, MI, or rehospitalization for unstable or progressive angina
PROSPECT: MACE
3-year follow-up, hierarchical
All
Culprit
Non culprit
lesion related lesion related
Indeterminate
Cardiac death
1.9% (12)
0.2% (1)
0% (0)
1.7% (11)
Cardiac arrest
0.3% (2)
0.3% (2)
0% (0)
0% (0)
MI (STEMI or NSTEMI)
2.7% (17)
1.7% (11)
1.0% (6)
0.2% (1)
Rehospitalization for unstable
or progressive angina
15.4% (101)
10.4% (69)
10.7% (68)
0.8% (5)
Composite MACE
20.4% (132)
12.9% (83)
11.6% (74)
2.7% (17)
4.9% (31)
2.2% (14)
1.0% (6)
1.9% (12)
Cardiac death, arrest or MI
Rates are 3-yr Kaplan-Meier estimates (n of events)
PROSPECT: MACE
3-year follow-up, hierarchical
All
Culprit
Non culprit
lesion related lesion related
Indeterminate
Cardiac death
1.9% (12)
0.2% (1)
0% (0)
1.7% (11)
Cardiac arrest
0.3% (2)
0.3% (2)
0% (0)
0% (0)
MI (STEMI or NSTEMI)
2.7% (17)
1.7% (11)
1.0% (6)
0.2% (1)
Rehospitalization for unstable
or progressive angina
15.4% (101)
10.4% (69)
10.7% (68)
0.8% (5)
Composite MACE
20.4% (132)
12.9% (83)
11.6% (74)
2.7% (17)
4.9% (31)
2.2% (14)
1.0% (6)
1.9% (12)
Cardiac death, arrest or MI
Rates are 3-yr Kaplan-Meier estimates (n of events)
PROSPECT: Multivariable Correlates
of Non-Culprit Lesion Related Events
Independent predictors of patient level
events by Cox Proportional Hazards
regression
Variable
HR [95% CI]
P value
Insulin dependent
diabetes
3.32 [1.43, 7.72]
0.005
Prior PCI
2.03 [1.15, 3.59]
0.02
Variables entered into the model: age, gender, hypertension, insulin dependent
diabetes, prior PCI, CRP at baseline, family history
PROSPECT: Multivariable Correlates
of Non-Culprit Lesion Related Events
Independent predictors of lesion level events
by Cox Proportional Hazards regression
Variable
HR [95% CI]
P value
PBMLA ≥70%
5.03 [2.51, 10.11]
<0.0001
VH-TCFA
3.35 [1.77, 6.36]
0.0002
MLA ≤4.0 mm2
3.21 [1.61, 6.42]
0.001
Variables entered: minimal lumen area (MLA), plaque burden at the MLA, external elastic membrane at the
MLA, lesion length, distance from the coronary ostium to the MLA, remodeling index, thin-cap fibroatheroma,
insulin-requiring diabetes and prior percutaneous coronary intervention
PROSPECT: Correlates of
Non-Culprit Lesion Related Events
Median 3.4 yr MACE rate
per lesion (%)
Number of factors present: PBMLA ≥70%, MLA ≤4.0mm2 or TCFA
20
18.2
15
10.5
10
4.8
5
0.3
0
Zero
One
Two
Three
5/1650
46/1059
24/253
5/29
PB = plaque burden at the MLA
PROSPECT: VH-TCFA and NonCulprit Lesion Related Events
Lesion HR
3.90 (2.25, 6.76)
P value
<0.0001
Prevalence*
46.7%
6.55 (3.43, 12.51)
<0.0001
15.9%
10.83 (5.55, 21.10)
<0.0001
10.1%
11.05 (4.39, 27.82)
<0.0001
4.2%
*Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA
PROSPECT: Thick CFA and NonCulprit Lesion Related Events
Lesion HR
0.92 (0.52, 1.63)
P value
0.77
Prevalence*
67.6%
3.41 (1.75, 6.65)
0.0003
22.7%
5.17 (2.59, 10.32)
<0.0001
15.6%
5.02 (1.99, 12.63)
<0.0001
8.3%
*Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA
PROSPECT: Non Fibroatheromas
and Non-Culprit Lesion Events
Pathological
Intimal
thickening
Lesion HR 0.22 (0.10, 0.49)
P value
0.0002
Prevalence*
67.9%
Fibrotic
1.22 (0.44, 3.39)
0.70
19.7%
Fibrocalcific
1.25 (0.17, 9.01)
0.83
5.6%
2.60 (0.36, 18.84)
0.34
2.7%
*Likelihood of one or more such lesions being present per patient. PB = plaque burden at the MLA
PROSPECT: Questions
Was 3-vessel VH-IVUS imaging safe?
Complications adjudicated to the 3-vessel IVUS imaging procedure (n=697)
Death
MI
0 (0%)
3 (0.4%)
- Q-wave (from dissection)
1
- non Q-wave (from dissection)
2
PCI or CABG
10 (1.4%)
- CABG (from perforation)
1
- CABG (from dissection)
2
- PCI (from dissection)
9
Any imaging complication*
*Some pts had more than one complication
11 (1.6%)
PROSPECT: Questions
How much disease was left behind after the
original PCI in 697 patients?
By IVUS (n=673)
1,814 untreated lesions
(visual DS >30%)
in the entire coronary tree
- mean 2.6 ± 1.8 per pt -
3,160 untreated lesions
(PB ≥40%) in the proximalto-mid coronary tree
- mean 4.7 ± 2.0 per pt -
QCA
DS%
DS <50%
N=1704
(93.9%)
DS ≥50%-<70%
N=98
(5.4%)
DS ≥70%
N=12
(0.7%)
Proportion of IVUS
lesions (%)
By angiography
25
20
19.6
mean 0.9 ± 1.1 per pt
15
9.0
10
5
N=620
mean
0.4 ± 0.7
N=283 per pt
0
DS% mean 33.7 ± 15.7%
MLA ≤4.0mm2
Plaque
burden ≥70%
PROSPECT: Questions
How much disease was left behind after the
original PCI in 697 patients?
By VH-IVUS (n=623)
2,811 untreated classified
lesions in the proximal-tomid coronary tree
TCFA
N=596 (21.9%)
ThCFA
N=1018 (37.3%)
0.98 ± 1.31 per pt
(range 0 – 7 per pt)
Fibrotic
N=104 (3.8%)
Fibrocalcific
N=33 (1.2%)
PIT
N=1008 (37.0%)
PROSPECT: Questions
What were the baseline angiographic characteristics of the
lesions that were later responsible for non-culprit events?
The mean angiographic QCA DS of the 106 lesions subsequently
responsible for non-culprit MACE in 76 pts was 32.3% ± 20.6% at baseline
and 65.4% ± 16.3% at the time of the follow-up event (P<0.001).
Baseline QCA %DS
32 lesions (30.2%) were angiographically
inconspicuous (<30% stenotic) by visual assessment)
Lesion location
Prox
Mid
Distal
Branch
24.3%
19.6%
15.9%
40.2%
PROSPECT: Questions
What were the baseline VH-IVUS characteristics of the
lesions that were later responsible for non-culprit events?
Baseline IVUS was performed in 55/106 sites that subsequently resulted in non-culprit
MACE. All 55 sites had plaque burden ≥40% by baseline IVUS imaging. Conversely,
no imaged coronary segment with <40% plaque burden resulted in a non-culprit event
during the median 3.4 year FU period.
51 non-culprit MACE lesions with baseline VH-IVUS
Not
TCFAs
N=25
(49%)
TCFAs
N=26
(51%)
PB ≥70% and/or
MLA ≤4.0mm2
N=18 (35%)
TCFA only
N=8 (16%)
PB ≥70% and/or
MLA ≤4.0mm2
N=20 (39%)
18 ThCFA
6 PIT
1 FC
0F
Not TCFA only
N=5 (10%)
PROSPECT: Questions
What types of events were responsible for
CULPRIT lesion MACE during follow-up?
• Stent thrombosis (n=13 lesions)
• Restenosis (n=107 lesions)
• New stent-related sidebranch lesions (n=5 lesions)
Baseline grayscale and VH-IVUS will be analyzed for correlates of future events
Possible predictors of stent thrombosis
FA behind stent
Totally
covered FA
Partially
uncovered FA
FA behind stent,
abutting into lumen
Separate
untreated
adjacent FA
PROSPECT: Implications
• Following successful and uncomplicated PCI in pts with ACS
who undergo careful clinical FU, is 3-vessel VH-IVUS to
identify and prophylactically stent non-culprit lesions at high
risk for future MACE warranted based on PROSPECT?
►No
1. The prevalence of high-risk lesions is relatively low
(~1 in 4 pts).
2. 3-vessel imaging is not risk-free (1.6% major
complication rate).
3. When high-risk lesions become symptomatic they
usually present with angina and not death or MI.
►This suggests that absent a randomized trial, optimal
medical therapy and close follow-up is more appropriate.
PROSPECT: Implications
• What if during routine IVUS-guided stenting (e.g. in the
MLAD), a high-risk non ischemia-producing lesion happens
to be found (e.g. a TCFA with PB of 75% in the PLAD) – is
prophylactic stenting justified?
►No
1. As long as the patient is medically compliant and is
closely followed, when high-risk lesions become
symptomatic they usually present with progressive
angina and not death or MI.
►A randomized controlled trial is required to demonstrate
the safety and efficacy of prophylactic stenting of non
ischemia-producing lesions before this practice can be
recommended.
PROSPECT: Implications
• So where should our efforts for future investigation be
focused?
• The prognosis for pts with ACS after successful PCI who
are medically compliant is favorable.
• However, millions of persons per year who have not been
diagnosed with CAD and are not receiving optimal
medical therapy die, arrest or develop MI every year.
►This suggests that future investigation should focus on
identifying asymptomatic or minimally symptomatic pts
with large plaque burden, small MLA and TCFAs through
noninvasive screening (e.g. MSCT), for intensive
medical therapy and possibly invasive imaging and Rx.