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Reevaluation of the 80%
Carotid Stenosis in
Asymptomatic Patients in
2011
Kenneth Rosenfield, MD, FACC, FAHA
Section Head, Vascular Medicine and Intervention
Massachusetts General Hospital
Boston, Massachusetts, U.S.A.
Kenneth Rosenfield, MD
Conflicts of Interest
•
•
Consultant
– Abbott Vascular
– Complete Conference
Management
– Harvard Clinical Research
Institute
– Lumen
– Micell
– Vortex
– VuMedi
Equity
– Icon
– CardioMEMs
– Contego
– Lumen
– Medical Simulation Corporation
– Micell
– Primacea
– VuMedi
•
•
Research or Fellowship Support
– Abbott Vascular
– Atrium
– Bard
– Baxter
– IDEV
– Invatec-Medtronic
– Lutonix
Board Member
– VIVA Physicians
• www.vivapvd.com
The asymptomatic lesion - 2011
1) Your 78 year old mother has an asx 80% stenosis of the Lt
Carotid artery by DUS. She is otherwise in good
health. You would:
a) Intensify medical therapy, adding statins, ASA, etc.
b) do (a) plus CEA (assume experienced surgeon)
c) do (a) plus CAS (assume experienced stenter)
d) allow her to choose either a, b, or c, based on her own
preference
Responses:
• c if good anatomy, stent it
• b.
• d but depends on anatomy; could also follow on meds
and if worsening duplex then d
Question
What if her stenosis was 70%?
Question
What if she was 86 y.o.?
…more likely to Rx conservatively?
…more likely to stent than CEA?
...or the other way around?
Carotid Artery Disease
Patient subsets
Symptomatic
High-risk
Asymptomatic
High-risk
Symptomatic
Standard-risk
Asymptomatic
Standard-risk
Treatment of Asx Carotid Disease…
It’s clear this is a “moving target”
Medical therapy is improving.
Carotid stenting results have improved, due
to technologic advances, experience of
operators, and better case selection
But so is CEA improving…
 Difficult to integrate new data with old to
come up with best management for our
patients!
Carotid Artery Disease
The problem with this field
• Many stakeholders with interests that extend
beyond those of the patient
• Each stakeholder too easily falls into the
trap of seeing only what they want to see, to
enhance and support their preconceived
bias.
NATIONAL INPATIENT SAMPLE DATA
J Vasc Surg 2007;46:1112-8
Carotid Revascularization for Asx Pts
Legitimate questions in the current era
• Should any asx patient undergo revasc AT ALL???
– Medical therapy much improved now
• What degree of stenosis is appropriate to revasc???
– Higher grade -->hemodynamic compromise
– Lower grade --> plaque rupture
• By which modality, CEA or CAS???
– “Conventional” vs. “high-risk” for CEA
Reevaluation of the 80% stenosis
Question #1
• Is it appropriate to revascularize
any asymptomatic patient in the
current era?
THE WALL STREET JOURNAL
MARCH 3, 2009
Drug Therapy Gains Favor to Avert Stroke
By THOMAS M. BURTON
A major study nearing completion is expected to help resolve a longstanding debate over whether surgery
or the insertion of a flexible stent is the better way to prevent stroke for people with blocked arteries in
the neck.
But
the many
study doesn't
aim to may
answerbe
another
pressing
question: How
many patients
may be better off
How
patients
better
off avoiding
those
risky procedures
avoiding those risky procedures altogether? An influential group of doctors say there is growing evidence
altogether?
An influential group of doctors say there is growing evidence
that certain drugs could be of benefit greater than or equal to surgery or stents in preventing stroke -thatmuch
certain
drugs
could
beinclude
of benefit
or equal
to surgery
or
with
reduced
risk. These
drugs
statins --greater
commonlythan
associated
with treating
high
cholesterol
as well as blood-pressure
and anticlotting
stents in--preventing
stroke --medications
with much
reduceddrugs
risk.such as aspirin.
The problem, these doctors say, is that unless a single study is done in which patients are randomly
assigned to one of the three therapies, it's impossible to judge what is the best option for most patients.
At the International Stroke Conference in San Diego last week,
"I've commonly had people come in for a second opinion after surgery or a stent was recommended,"
researchers
presented
stroke-specific
data from
the
recent
says
Frank J. Veith,
a vascular surgeon
at New York University
Medical
Center.
"Afterheart-disease
I explain the risks
from
procedurestrial
and the
possibleas
benefits,
almost
all of them
opt for statins."
prevention
known
Jupiter,
which
involved
17,802 patients. Patients
taking
Crestor…had
a 48%
intherisk
of stroke
At
issue are
strokes caused when
clots ordecrease
fatty plaque in
carotid
arteries begin to impede blood flow
to the brain. A glob of this debris can dislodge, float up into the brain and block any of several small
arteries there. Brain-tissue death can begin quickly, leaving patients with a range of outcomes from mild
impairment to paralysis or death. Doctors say carotid-artery blockage plays a role in as many as half the
780,000 strokes that occur in the U.S. each year. Other factors that cut oxygen flow to the brain account
SPARCL: High Dose Atorvastatin vs Placebo
In Patients with Prior CVA/TIA
Stroke or TIA
N Engl J Med 2006;355:549-559
13
14
Curr Opin Neurol 2007;20:58-64
Optimal Medical Therapy
Trials forming basis for “new paradigm” of therapeutic nihilism
about revasc all have issues:
1. pt cohorts- prior CVA patients
2. endpoint of “all-cause stroke”, not carotid stroke
That said, there is NO DOUBT, OMT is better now
BUT…
• CEA and CAS results have improved as well
• Benefits of new OMT may be additive to revasc
• No Level I evidence to support a strategy of Med Rx only (w/o
revasc) for those at risk for stroke from carotid stenosis
• It is inappropriate (and unscientific) to simply assume that
OMT alone is better now than revasc plus OMT…one cannot
simply discard the level I evidence accrued in prior trials
The other problem with Med Therapy
MARCH 3, 2009
Drug Therapy Gains Favor to Avert Stroke
By THOMAS M. BURTON
A major study nearing completion is expected to help resolve a longstanding debate over whether surgery
or the insertion of a flexible stent is the better way to prevent stroke for people with blocked arteries in
the neck.
But the study doesn't aim to answer another pressing question: How many patients may be better off
avoiding those risky procedures altogether? An influential group of doctors say there is growing evidence
a
that certain drugs could be of benefit greater than or equal to surgery or stents in preventing stroke -Harvard
professor and medical director of the Massachusetts General
with much reduced risk. These drugs include statins -- commonly associated with treating high
Hospital's
center. However,
"It isdrugs
well-known
that many
cholesterol --vascular
as well as blood-pressure
medicationshe
andsaid:
anticlotting
such as aspirin.
"I'm a big believer in medical therapy," says Michael R. Jaff,
patients
who require drug therapy either don't get it, don't get treated to goal
The problem, these doctors say, is that unless a single study is done in which patients are randomly
[to
achieve
numbers
cholesterol
and
blood
pressure]
are
not
assigned
to onetarget
of the three
therapies,for
it's impossible
to judge
what
is the best
option for or
most
patients.
compliant with their meds."
"I've commonly had people come in for a second opinion after surgery or a stent was recommended,"
says Frank J. Veith, a vascular surgeon at New York University Medical Center. "After I explain the risks
from procedures and the possible benefits, almost all of them opt for statins."
At issue are strokes caused when clots or fatty plaque in the carotid arteries begin to impede blood flow
to the brain. A glob of this debris can dislodge, float up into the brain and block any of several small
arteries there. Brain-tissue death can begin quickly, leaving patients with a range of outcomes from mild
impairment to paralysis or death. Doctors say carotid-artery blockage plays a role in as many as half the
780,000 strokes that occur in the U.S. each year. Other factors that cut oxygen flow to the brain account
Carotid Stenosis Procedures
in Medicare Fee for Service Population
100,000
90,000
80,000
Carotid
Endarterectomy
70,000
60,000
50,000
Carotid Stenting
40,000
30,000
20,000
10,000
0
2001
2003
2005
2006
2007
2008
Stroke Prevention by Revascularization
What is the evidence…
• RCT:
– CEA beats medical Rx* in standard
surgical risk patients
– CAS equals CEA in high surgical risk
patients
ACST - Early vs. Deferred Carotid Endarterectomy in
Asymptomatic Patients with ICA Stenosis
Any Stroke or Perioperative Death
Time (years) 
Benefit of Med Rx with Revascularization over Med Rx alone
ACST Investigators. Lancet 2004;363:1491-1502
CEA vs. Med Rx for Stroke Prevention
Recommendation based on Asx RCT’s (Level I)
• CEA, on top of contemporary medical therapy,
is beneficial in selected (“e.g. conventional
risk”) patients, ages 40-75 years, who are
expected to live for >5 years, if:
–
Stenosis 60-99% and physician/hospital
stroke/death rate < 3%
-AHA/ASA Guideline; Stroke, Feb06
Optimal Medical Therapy alone vs Revasc
Trials forming basis for “new paradigm” of therapeutic nihilism
about revasc all have issues:
1. pt cohorts- prior CVA patients
2. endpoint of “all-cause stroke”, not carotid stroke
• No Level I evidence to support a strategy of Med Rx only (w/o
revasc) for those at risk for stroke from carotid stenosis
• It is inappropriate (and unscientific) to simply assume that
OMT alone is better now than revasc plus OMT…one cannot
simply discard the level I evidence accrued in prior trials
Reevaluation of the 80% stenosis
Question #2
• Which mode of revascularization
should I offer? Is CAS equal to
CEA now?
Therapy for for stroke prevention:
RCT’s: CAS vs. CEA
completed*
SAPPHIRE *
Symptomatic
High-risk
ongoing
Asymptomatic
High-risk
KENTUCKY *
Symptomatic
Standard-risk
Asymptomatic
Standard-risk
EVA3s, SPACE 1 *
ACT 1, SPACE 2
CREST *
SAPPHIRE 3-Year Outcomes
Freedom from MAE
N Engl J Med 2008;358:1572-9
SAPPHIRE Asymptomatic: 360-Day MAE
(ITT)
CEA (n=120)
25
Stent (n=117)
19.2
20
P=0.07
15
%
P=0.15
P=1.00
10.8
10
7.5
7.7
P=0.08
10.3
8.3
5.1
5
2.6
0
Death
Stroke
MI
MAE
Real world outcomes for asx high risk patients: AHA
guidelines met or exceeded by >500 operators
(never demonstrated by CEA)
N=4282
(%) Subjects
EXACT/CAPTURE 2 (combined): 30-day major adverse events
asymptomatic patients <80 years
8
7
6
5
4 3% AHA guideline
3
2
2.9
1
1.1
0
Death/Stroke
Death/Major Stroke
1.8
0.8
Death
0.6
Stroke Minor (1.8%)
Stroke Major (0.6%)
Gray et al., Circ Cardiovasc Intervent
2009; March 6
Stroke Prevention by Revascularization
What is the evidence…
• RCT:
– CEA beats medical Rx* in standard
surgical risk patients
– CAS equals CEA in high surgical risk
patients
NOW:
– CAS equals CEA in standard surgical risk
patients
Primary endpoint ≤4 years (mean 2.5)
Peri-procedural outcomes
7.2
P=0.38
P=0.51
6.8
1.18 95%
95% CI:
CI: 0.81-1.51
0.82-1.68
HR 1.11
Peri-procedural Stroke and MI
PValue
CAS vs. CEA Hazard Ratio 95% CI
All
Stroke
4.1 vs. 2.3%
HR = 1.79; 95% CI: 1.14-2.82
0.01
MI
1.1 vs. 2.3%
HR = 0.50; 95% CI: 0.26-0.94
0.03
Cranial Nerve Palsies
CAS vs. CEA
Hazard Ratio, 95% CI
P-Value
0.3 vs. 4.7%
HR = 0.07; 95% CI: 0.02-0.18 <0.0001
CREST: Additional STRIKING Info from
Recent FDA Panel Meeting
• Primary endpoint rate lower with EPD
• Minor strokes – residual deficits equal b/n
CAS and CEA at 6 mos
• Incidence of death and major stroke in CAS
was almost ZERO for last half of trial (for
Symptomatics, it WAS zero)
• Effect of MI on survival – 25% mortality (vs.
minor stroke 5% mortality in same timeframe) – MI had essentially same effect as
Major stroke
ACT I: Outcomes
Lead In Patients
Event
30 days, N=180
Death, Stroke and MI
1.7% (3/180)
All Stroke and Death
1.7%
Major Stroke and Death
0.0%
Death
0.0%
All Stroke
1.7%
Major Stroke
0.0%
Minor Stroke
1.7%
MI
0.0%
31-365 days, N=157
Ipsilateral Stroke
32
0.0%
Higher Risk for CAS:
Calcification and Ulceration
Heavy concentric
calcification
ECVD Guidelines 2011
Recommendations re: revasc modality
Symptomatic Symptomatic
patients
patients
Asymptomatic
patients
50-69%
stenosis
70-99%
stenosis
70-99%
stenosis
CEA
Class I
LOE: B
Class I
LOE: A
Class IIa
LOE: A
Stent
Class I
LOE: B
Class I
LOE: B
Class IIb
LOE: B
Bottom Line…
• Number of patients who have had CAS is now in
the hundreds of thousands
• Proven to be safe and effective procedure that is
comparable to CEA
• Results have improved with time…better
operators, better case selection, and better
equipment
• Level I evidence to support CAS as equivalent to
CEA
• Time for FDA and CMS to approve coverage
• Decision regarding therapy should be
individualized for each patient; pts deserve choice
What about the patient’s point of view?
MARCH 3, 2009
Drug Therapy Gains Favor to Avert Stroke
By THOMAS M. BURTON
Surgery
clearly has benefits for some patients, especially
A major study nearing completion is expected to help resolve a longstanding debate over whether surgery
when
previous
Bill
McDonough,
of with blocked arteries in
or the insertion
of a symptoms
flexible stent is exist.
the better
wayC.
to prevent
stroke for people
the neck. Mass., suffered a ministroke in August. Doctors
Canton,
found
artery
on another
one side
of his
neck
had
99%
But thethe
studycarotid
doesn't aim
to answer
pressing
question:
How
many
patients may be better off
avoiding those
riskythe
procedures
An influential
of doctors
say there is growing evidence
blockage,
and
arteryaltogether?
on the other
side,group
96%.
The 59that certain drugs could be of benefit greater than or equal to surgery or stents in preventing stroke -year-old
retired banker checked in to Massachusetts
with much reduced risk. These drugs include statins -- commonly associated with treating high
General
had surgery
on one
artery and
cholesterolHospital
-- as well asand
blood-pressure
medications
and anticlotting
drugs such as aspirin.
chose
to have a stent placed in the other. Mr. McDonough
The problem, these doctors say, is that unless a single study is done in which patients are randomly
said
he to
isone
"100%
better"
now.it's impossible to judge what is the best option for most patients.
assigned
of the three
therapies,
"I've commonly had people come in for a second opinion after surgery or a stent was recommended,"
says Frank J. Veith, a vascular surgeon at New York University Medical Center. "After I explain the risks
from procedures and the possible benefits, almost all of them opt for statins."
At issue are strokes caused when clots or fatty plaque in the carotid arteries begin to impede blood flow
to the brain. A glob of this debris can dislodge, float up into the brain and block any of several small
arteries there. Brain-tissue death can begin quickly, leaving patients with a range of outcomes from mild
impairment to paralysis or death. Doctors say carotid-artery blockage plays a role in as many as half the
780,000 strokes that occur in the U.S. each year. Other factors that cut oxygen flow to the brain account
Thank you!