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T h e NE W ENGL A ND JOUR NA L o f MEDICINE

CLINICAL PRACTICE
Secondary Prevention after Isce!ic Stro"e
or Transient Isce!ic Attac"
Stephen M. Davis, M.D., and Geoffrey A. Donnan, M.D.
This Jo#rna$ feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal
guidelines, when they exist. The article ends with the authors’ clinical recommendations.
From the Melbourne Brain Centre, Royal
Melbourne Hospital S.M.D.!" the Depart#
ments of Medi$ine S.M.D.! and %eurol#o&y
S.M.D., G.A.D.!, 'niversity of Mel#bourne"
and the Florey %euros$ien$e (nstitutes
G.A.D.! ) all in Melbourne, *(C, Australia.
Address reprint re+uests to Dr. Davis at the
Melbourne Brain Centre, Royal Melbourne
Hospital, ,ar-ville, *(C, Australia ./0/, or
at stephen.davis1mh
.or&.au.
% 2n&l 3 Med 4/54".6675859#44.
Copyright © 2012 Massachusetts Medical Society.
An audio
version of this
article is
available at
NEJM.org
A 62-year-
old woman
is seen 1
week after
an ischemic
stroke. She
had
presented to
another
hospital
with
dysphasia
and right-
sided
weakness;
magnetic
resonance
imag-ing
(MR!
showed a
recent
infarction in
the left
parietal
corte"# and
comp$ted
tomo-
graphic
angiography
(%&A!
showed a
high-grade
stenosis in
the left
pro"imal
internal
carotid
artery with
normal
intracranial
'essels ((ig.
1!. She was
treated with
intra'e-no$s
recom)inan
t tiss$e plasminogen acti'ator and
discharged home# taking aspirin
and a statin. She stopped smoking
12 years ago. *n e"amination# the
)lood press$re is 1+,-./ mm 0g.
She reports some mild resid$al
cl$msiness of her right hand.
1hat wo$ld yo$ ad'ise to red$ce
the risk of stroke rec$rrence2
T%E
CLIN
ICAL
PRO&
LEM
Wor$d'ide( stro"e is te second
!ost co!!on ca#se of deat
after !yocardia$ in)farction and
is a $eadin* ca#se of ac+#ired
disa,i$ity- In so!e re*ions( te
co!),ined incidence of stro"e
and transient isce!ic attac"s
.TIAs/ e0ceeds te incidence of
coronary vasc#$ar events-
1
More
tan 234 of fata$ stro"es occ#r
in $o') and !id)d$e)inco!e
co#ntries-
5(6
Patients 'it stro"e are at i*
ris" for s#,se+#ent vasc#$ar
events( inc$#din* rec#r)rent stro"e
.i*est ris"/( !yocardia$
infarction( and deat fro!
vasc#$ar ca#ses- &eca#se te ris"
of stro"e is i*est in te ear$y
7eriod after te ac#te event(
7ro!7t initiation of tai$ored
7revention strate*ies is essentia$-
8
A !eta)ana$ysis so'ed tat te
ris" of stro"e 'as as i* as
15-24 d#rin* te first 'ee" after
a TIA( ,#t te ris" 'as $o'est
'en e!er*ency treat!ent ad
,een *iven ,y s7ecia$i9ed stro"e
ser)vices-
8
It is esti!ated tat at
$east 2:4 of rec#rrent events
!i*t ,e 7revented 'it te #se
of a co!7reensive a77roac tat
inc$#des dietary !odification(
e0ercise( ,$ood)7ress#re
$o'erin*( anti7$ate$et tera7y(
and statin tera7y-
8(3
STR
ATEGIES
AND
E;IDE
NCE
EVALUATION
Stro"e is
cate*ori9ed as
isce!ic stro"e
.2:4 of cases/(
intracere,ra$
e!orra*e
.134/( or
s#,aracnoid
e!orra*e
.34/-
'ere
traditiona$$y
defined as ,rief
ne#ro$o*ic
e7isodes of
vasc#$ar ori*in
$astin* $ess tan
58 o#rs- More
recent$y( TIAs
ave ,een
c$assified as
transient ne#ro$o*ic events
'ito#t si*ns of ac#te
infarction on i!a*in*-
#7dated definition is ,ased
on te evidence tat !any
stro"es de)tected on
i!a*in*( 7artic#$ar$y MRI(
$ast $ess tan 58 o#rs or are
c$inica$$y si$ent- Tis revie'
foc#ses on secondary
7revention after a TIA or
isce!ic stro"e-
1<18
% 2%G: 3
M2D
.66"4/
%23M.;R
G MA<
5=, 4/54
The New England Journal of
Medicine
D
o
w
n
l
o
a
d
e
d
f
r
o
m

n
e
j
m
.org on
August 8,
2012. For
personal
use only.
No other
uses
without
permission
.
Copyri
ght ©
2012
Massa
chusett
s
Medic
al
Societ
y. All
rights
reserv
ed.
CLINICAL PRACTICE
I
n
7$a
nni
n*
sec
on
dar
y
7re
ve
nti
on(
it
is
i!
7or
)
tan
t to
att
e!
7t
to
ide
ntif
y
te
7at
o
*e
nes
is
of
te
TI
A
or
isc
e
!i
c
str
o"
e(
7ar
tic
#$a
r$y
to
det
ect
c$i
nic
a$$
y
si*
nifi
can
t
cardiac
or
$ar*e)
artery
ca#ses
tat
'arrant
te #se
of
strate*i
es
tai$ored
to te
individ
#a$
7atient-
In
c$inica$
7ractic
e( te
Tria$ of
Or*
1:1=5
in
Ac#te
Stro"e
Treat!
ent
.TOAS
T/
c$assifi
cation
for
isce!
ic
stro"e
is
#sef#$
in de)
$ineatin
*
!a>or
7ato*
eneses
on te
,asis
of
c$inica$
findin*
s and
investi
*ations
-
=
Tese
in)
c$#de
cardioe
!,o$is
!
.!ost
co!!o
n$y
fro!
atri)a$
fi,ri$$at
ion/(
$ar*e)
artery
disease
( s!a$$)
vesse$
occ$#si
on
.$ac#na
r
stro"e/(
stro"e
of
oter
deter)
!ined
ca#se
.e-*-(
arteria$
dissecti
on(
dr#*)
re$ated
stro"e(
or a
y7erc
oa*#$a
,$e
disorde
r/( and
stro"e
of
#ndeter
!ined
ca#se
.t'o or
!ore
identifi
ed
ca#ses
or
ne*ativ
e or
inco!7
$ete
eva$#at
ion/-
Even
'en
f#$$y
investi
*ated(
#7 to
6:4 of
cases
of ce)
re,ra$
isc
e
!i
a
re
!a
in
#n
e0
7$a
ine
d
.?c
ry7
to*
en)
ic
str
o"
e@/
-
U
r*e
nt
eva
$#a
tio
n
is
'a
rra
nte
d
aft
er
a
str
o"
e
or
TI
A(
,ec
a#s
e
!a
ny
rec
#rr
ent
eve
nts
occ
#r
ear
$y-
&r
ain
i!
a*i
n*
is
!andat
ory for
dia*no
sis(
c$assi)
fication
( and
!ana*
e!ent-
MRI is
!#c
!ore
sensitiv
e tan
co!7#t
ed
to!o*r
a7y
.CT/ in
te
dia*no
sis of
ac#te
isce!
ia(
a$to#*
CT is
!ore
'ide$y
avai$a,
$e-
Arteria
$
i!a*in
* 'it
te #se
of
carotid
Do77$e
r
#$traso
no*ra7
y(
CTA(
or
!a*)
netic
resona
nce
an*io*r
a7y
.MRA/
is
#s#a$$y
necessa
ry- In
!any
centers
( CT is
no'
co!,in
ed 'it
CTA-
E$ectro
cardio*
ra7y
is
ro#tine
$y 7er)
for!ed
- To
detect
7aro0y
s!a$
atria$
fi,ri$$at
ion(
a!,#$a
tory
!onito
rin* is
#sef#$-
Transt
oracic
or
transes
o7a*e
a$
ecoca
rdio*ra
7y is
often
#sed to
detect
cardiac
so#rces
of
e!,o$i
s!
oter
tan
atri
a$
fi,
ri$$
ati
on-
Ro
#ti
ne
,$o
od
tes
ts
!a
y
rev
ea$
7re
dis
7o
sin
*
ca
#se
s(
s#c

as
7o$
yc
yt
e!
ia(
ren
a$
i!
7ai
r!
ent
(
e$e
ctr
o$y
te
dis
t#r
,a
nc
es(
an
d
y
7er
)
*$y
ce
!i
a-
M
ANAG
EMEN
T
A**res
sive
ris")
factor
!ana*
e!ent
and
$ifesty$
e
advice
are
essenti
a$ for
a$$
7atient
s-
O,serv
ation)a$
st#dies
of
7atient
s 'it
a
istory
of
stro"e
in)
dicate
tat
ea$ty
$ifesty$
e
,eavi
ors(
inc$#di
n*
re*#$ar
e0ercis
e and
a,stine
nce
fro!
s!o"in
*( are
associa
ted
'it
red#ce
d
!orta$i
ty-
2(<
In
te
INTER
STRO
AE
caseB
contro$
st#dy
invo$vi
n* first
ac#te
stro"es
(
1:
1:
ris"
factors
acco#n
ted for
<:4 of
stro"e
ris"C
y7erte
nsion(
c#rrent
s!o"in
*( a
i*
'aist)
to)i7
ratio( a
i*
dietary
ris"
score(
$ac" of
re*#$ar
7ysica
$
activity
(
dia,ete
s
!e$$it#
s(
e0cess
a$coo$
cons#
!7tion(
7syco
socia$
stress
or
de7ress
ion(
cardiac
ca#ses
.e-*-(
7revio#
s !yo)
cardia$
infarcti
on or
atria$
fi,ri$$at
ion/(
and a
i*
ratio of
a7o$i7o
7rotein
& to
a7o$i7o
7rotein
A1-
1:
Dia,et
es and
te
!e
ta,
o$i
c
syn
dro
!e
are
co
!)
!o
n
in
7at
ien
ts
'it

str
o"
e
or
TI
A
an
d
!a
y
not
a
ve
,ee
n
7re
vio
#s$
y
rec
o*
ni9
ed-
I
n
second
ary
7reven
tion(
tree
7rinci7
a$
strat)
e*ies
are
a77ro7
riate
for
near$y
a$$
7atient
sC
,$ood)
7ress#r
e
$o'eri
n*(
co$est
ero$
$o'eri
n*
'it
statins(
and
anti7$a
te$et
tera7
y
.e0ce7
t in
7atient
s in
'o!
anticoa
*#$ant
tera7
y is
indicat
ed/-
Oter
strate*
ies are
s7ecifi
c to
te
ca#se
of
stro"e
.Ta),$e
1/-
BLOO
D-
PRES
SURE
LOWE
RING
&$ood
7ress#r
e is te
!ost
i!7ort
ant
!odifi
a,$e
ris"
factor
in ,ot
7ri!ar
y and
second
ary
7reven)
KEY CLINICAL POINTS
S
E
C
O
N
D
A
R
Y
P
R
E
V
E
N
T
I
O
N
A
F
TE
R
IS
C
HE
MI
C
ST
R
O
KE
O
R
TR
A
NS
IE
NT
IS
C
HE
MI
C
AT
TA
C
K
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% 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54
The New
England
Journal of
Medicine
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T h e NE W ENGL A ND JOUR NA L o f MEDICINE
tion of stro"e- O,servationa$ st#dies and c$inica$
A tria$s s#77ort ,$ood)7ress#re red#ction for sec)
ondary 7revention in !ost 7atients( re*ard$ess of
te initia$ ,$ood)7ress#re $eve$- Data are $ac"in*
to deter!ine te !ost effective ,$ood)7ress#re
tar*et and e0tent of $o'erin*( and *#ide$ines rec)
o!!end tat treat!ent ,e individ#a$i9ed( ,#t ,en)
efits ave ,een $in"ed to a,so$#te ,$ood)7res)
s#re red#ctions of a77ro0i!ate$y 1:D3 !! %*-
Given data s#**estin* te ris"s of i!!ediate
,$ood)7ress#re $o'erin* after stro"e( ca#tion is
'arranted in te ac#te care settin*-
A syste!atic revie' of tria$s of secondary 7re)
vention after stro"e 'it te #se of a*ents in
vario#s c$asses of antiy7ertensive dr#*s so'ed
red#ctions in a$$ stro"es( nonfata$ stro"es( !yo)
cardia$ infarction( and a$$ vasc#$ar eventsE te
!a*nit#de of te red#ction in stro"e ris" 'as
B
direct$y re$ated to te de*ree of systo$ic),$ood)
7ress#re $o'erin*-
a*ainst Rec#rrent Stro"e St#dy .PROGRESS/(
7atients 'it a 7rior stro"e or TIA 'ere rando!$y
assi*ned to treat!ent 'it an an*iotensin)con)
vertin*Ben9y!e .ACE/ ini,itor .7$#s te di#retic
inda7a!ide( at te discretion of te 7ysician/ or
7$ace,o- Tere 'as a 524 $o'er ris" of stro"e over
a 7eriod of 8 years in te ACE)ini,itor *ro#7(
'it an avera*e ,$ood)7ress#re red#ction of
<D8 !! %*- Data fro! anoter $ar*e tria$ invo$v)
in* i*)ris" 7atients( inc$#din* tose 'it a 7rior
stro"e( a$so s#77ort ,$ood)7ress#re $o'erin* 'it
an ACE ini,itor-
Weter te ,enefits of ,$ood)7ress#re $o'er)
in* de7end on te 7artic#$ar c$ass of antiy7erten)
sive dr#*s or si!7$y on te antiy7ertensive effect
of a$$ s#c dr#*s re!ains controversia$( a$to#*
!ost of te evidence a77ears to s#77ort te $at)
ter-
53
Te PROGRESS tria$ so'ed a *reater red#c)
tion in te ris" of stro"e and oter vasc#$ar o#t)
co!es a!on* 7atients treated 'it a co!,ination
of an ACE ini,itor and a di#retic tan a!on*
tose treated 'it an ACE ini,itor a$one( ,#t
,$ood)7ress#re red#ction 'as *reater 'it co!,i)
nation tera7y-
11
so'ed a red#ction in te co!,ined incidence of
stro"e and TIA 'it an an*iotensin)rece7tor ,$oc")
er .AR&/ as co!7ared 'it a ca$ci#! anta*onist(
Figure 1. I!gi"g S#u$ie% i" ! W&!" 'i#( !" I%)(ei) des7ite si!i$ar effects on ,$ood 7ress#re-
S#r&*e.
a !#c $ar*er tria$( te Prevention Re*i!en for
(n ,anel A, a diffusion#>ei&hted MR( s$an sho>s an
Effective$y Avoidin* Second Stro"es .PRoFESS/
a$ute infar$tion in the territory of the left middle $ere#
st#dy( fai$ed to so' a si*nificant ,enefit of an bral artery. (n ,anel B, C?A sho>s severe stenosis of
the left internal $arotid artery arro>!. AR& over 7$ace,o in red#cin* te ris" of rec#r)
1<1G
rent stro"e
5=
E o'ever( te ne*ative res#$ts !ay
% 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54
The New England Journal of
Medicine
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Copyright © 2012
Massachusetts
Medical Society.
All rights
reserved.
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T!+,e 1.
S#r!#egie%
&- Pr&.e"
Be"e-i# -&r
Se)&"$!r/
Pre.e"#i&
" &-
S#r&*e.0
I"$i)!#i&" !"$ S#r!#eg/
RoutineB
Blood#pressure lo>erin&
Cholesterol lo>erin& statin!
Antiplatelet therapy unless anti
Aspirin first#line therapy!
Clopido&rel
Aspirin plus dipyridamole
Symptomati$ hi&h#&rade stenosis7 $arotid endartere$tomy
Atrial fibrillation
Carfarin
Dabi&atran
Rivaro@aban
Api@aban
1* All
trials are
based on
level 5
eviden$e.
?he list of
trials is not
$omprehen
sive"
instead, a
definitive
trial or
meta#
analysis is
$ited for
ea$h
intervention.
?he number
needed to
t
r
D

B

1
1
C
L
I
N
I
C
A
L

P
R
A
C
T
I
C
E
1
<
1
=
T h e NE W ENGL A ND JOUR NA L o f MEDICINE
ave ,een e07$ained ,y te s!a$$ red#ction in day/ a77ear to ,e as effective as i*er doses in
,$ood 7ress#re 'it active treat!ent-
5=
red#cin* te ris" of stro"e( 'it a $o'er ris" of
*astrointestina$ to0ic effects-
CHOLESTEROL LOWERING WITH STATINS Secondary)7revention tria$s ave a$so so'n
Co$estero$ $o'erin* 'it statin dr#*s( 'ic is ,enefits of oter anti7$ate$et strate*ies- &ot c$o
effective in 7ri!ary stro"e 7revention( as a$so 7ido*re$ .an adenosine di7os7ateBrece7tor in)
7roved effective in secondary 7revention after i,itor/
13
and te co!,ination of as7irin 7$#s di)
stro"e or TIA- A s#,*ro#7 ana$ysis invo$vin* 7a) 7yrida!o$e .a 7os7odiesterase ini,itor/
tients 'it a istory of cere,rovasc#$ar disease in 'ere so'n in rando!i9ed tria$s to ,e s#7erior to
te %eart Protection St#dy 'it an initia$ tota$ as7irin( ,#t te a,so$#te ,enefits 'ere very s!a$$-
co$estero$ $eve$ of at $east 163 !* 7er deci$iter In a tria$ co!7arin* te co!,ination of as7irin
.6-3 !!o$ 7er $iter/ so'ed tat si!vastatin .at a 7$#s di7yrida!o$e 'it c$o7ido*re$ for te 7re)
dose of 8: !* 7er day/( as co!7ared 'it 7$ace) vention of rec#rrent stro"e( o#tco!es 'ere si!)
,o( res#$ted in a 5:4 red#ction in te ris" of a$$ i$ar in te t'o treat!ent *ro#7s-
vasc#$ar end 7oints and a 534 red#ction in te $ines indicate tat as7irin a$one( c$o7ido*re$( and
ris" of stro"e-
52
In te Stro"e Prevention ,y A*) as7irin 7$#s di7yrida!o$e are a$$ acce7ta,$e first)
*ressive Red#ction in Co$estero$ Leve$s .SPARCL/ $ine o7tions in secondary stro"e 7revention-
st#dy(
15
a 7$ace,o)contro$$ed tria$ invo$vin* 7a) do!i9ed tria$s ave so'n no ,enefit( and in)
tients 'it a recent TIA or stro"e and ,ase$ine creased e!orra*ic ris"s( 'it te co!,ined #se
$o')density $i7o7rotein .LDL/ co$estero$ $eve$s of c$o7ido*re$ and as7irin as co!7ared 'it c$o
of 1:: to 1<: !* 7er deci$iter .5-G to 8-< !!o$ 7ido*re$ a$one
66
or as7irin a$one
7er $iter/( tose rando!$y assi*ned to atorva secondary 7revention after stro"e- In te Sec)
statin .at a dose of 2: !* 7er day/ ad si*nificant ondary Prevention of S!a$$ S#,cortica$ Stro"es
red#ctions in te ris"s of stro"e and a$$ cardio) .SPS6E C$inica$Tria$s-*ov n#!,er( NCT:::3<6:G/
vasc#$ar events .a,so$#te ris" red#ctions( 5-5 7er) tria$( 'ic is eva$#atin* anti7$ate$et tera7y 'it
centa*e 7oints and 6-3 7ercenta*e 7oints( res7ec) as7irin 7$#s c$o7ido*re$ vers#s as7irin a$one( as
tive$y( over a 7eriod of 3 years/- Te ,enefits 'e$$ as t'o a77roaces to ,$ood)7ress#re $o'er)
a77ear to ,e *reatest in 7atients 'it te *reatest in*( te co!,ination anti7$ate$et tera7y 'as
red#ctions in LDL $eve$s .3:4 or !ore/-
5<
Second) recent$y ter!inated 7re!at#re$y o'in* to e0cess
ary)7revention *#ide$ines reco!!end treat!ent e!orra*es and deats-
for 7atients 'it an LDL co$estero$ $eve$ of 1:: !* Sort)ter! #se of te co!,ination of as7irin
7er deci$iter .5-G !!o$ 7er $iter/ or i*er( 'it and c$o7ido*re$ as ,een 7ro7osed ear$y after
te ai! of red#cin* te $eve$ ,y at $east 3:4 or stro"e or TIA( 'en te ris" of rec#rrent stro"e
acievin* a tar*et $eve$ of $ess tan =: !* 7er is i*est .Ta,$e 5/- A ,rief d#ration of e07os#re
deci$iter .1-2 !!o$ 7er $iter/-
2
Des7ite te overa$$ 'o#$d ,e e07ected to red#ce te ris"s associated
,enefit( statins ave ,een associated 'it a s$i*t$y 'it co!,ination tera7y- In a rando!i9ed( con)
increased ris" of intracere,ra$ e!orra*e( and tro$$ed 7i$ot tria$( te rate of stro"e rec#rrence at
teir #se !ay ,e contraindicated in 7atients 'it <: days 'as 1:-24 a!on* 7atients rando!$y
te disorder-
15(6:
assi*ned to as7irin 'itin 58 o#rs vers#s =-14
a!on* tose rando!$y assi*ned to co!,ined
ANTIPLATELET THERAPY as7irin and c$o7ido*re$E tis difference 'as not
Un$ess anticoa*#$ation is indicated( 7atients so#$d si*nificant( ,#t te tria$ 'as #nder7o'ered-
receive anti7$ate$et tera7y for secondary stro"e A $ar*er tria$ co!7arin* tese re*i!ens is #n)
7revention- In tria$s invo$vin* i*)ris" 7atients( der 'ay .NCT::<<1:5</-
inc$#din* tose 'it a istory of stro"e( as7irin
red#ced te ris" of s#,se+#ent vasc#$ar events CAROTID ENDARTERECTOMY AND CAROTID-ARTERY
overa$$ ,y a,o#t a +#arter-
16
%o'ever( a !eta) STENTING
ana$ysis of tria$s s7ecifica$$y of as7irin .vs- 7$a) Carotid endarterecto!y is indicated for te treat)
ce,o/( $i!ited to 7atients 'it a 7rior stro"e or !ent of 7atients 'it a istory of TIA or nondis)
TIA( s#**ested tat as7irin red#ced te ris" of a,$in* isce!ic stro"e 'o ave i*)*rade .=:
s#,se+#ent vasc#$ar events ,y on$y 164-
18
Lo' to <<4/ carotid stenosis or( in se$ected cases( !od)
doses of as7irin .ran*in* fro! =3 to 653 !* 7er erate .3: to G<4/ stenosis-
1<12 % 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54
The New England Journal of Medicine
Downloaded from nejm.org on August 8, 2012. For personal use only. No other uses without permission.
Copyright © 2012 Massachusetts Medical Society. All rights reserved.
CLINICAL PRACTICE
T!+,e 1. C&"#r&.er%i!, &r I".e%#ig!#i&"!, Se)&"$!r/-Pre.e"#i&" S#r!#egie%.0
T!rge# P&%%i+,e
S#r!#eg/
2arly re$urrent stro-e
Combined
aspirin and $lopido&rel for
8/ days
from
stro-e
onset
C&

e
"#%
(n$reased ris- >ith
$ombination therapy
vs. aspirin or
$lopido&rel alone, but
meta#analysis
su&&ests pos sible
benefit of
$ombination therapy
after a ?(A or minor
stro-e
.0
"
,;(%?
%C?//885/4
8!7
$ombination
therapy vs.
aspirin,
on&oin&
Carotid stenosis
Aorti$#ar$h atheroma
(ntra$ranial arterial stenosis
Carotid disse$tion
,atent foramen ovale
1* A
RCH
denotes
Aorti$
Ar$h
Related
Cerebral
HaAard,
CAD(SS
Cervi$al
Artery
Diss
e$tio
n in
Stro
-e
Stud
y,
C:;
S'R
2 (
2val
uatio
n of
the
S?A
RFle
@ Septal Closure System
in ,atients >ith a Stro-e
andEor ?ransient (s$hemi$
Atta$- due to ,resumed
,arado@i$al 2mbolism
throu&h a ,atent
Foramen ;vale, ,;(%?
,latelet#;riented
(nhibition in %e> ?(A and
Minor (s$hemi$ Stro-e,
and SAMM,R(S Stentin&
and A&&ressive Medi$al
Mana&ement for
,reventin& Re$urrent
Stro-e in (ntra$ranial
Stenosis.
A!erica
n
Sy!7to
!atic
Carotid
Endarter
ecto!y
Tria$
.NASCE
T/(
7artici7a
nts 'it
i*)
*rade ca)
rotid
stenosis
'o
'ere
rando!$
y
assi*ned
to end)
arterecto
!y ad
an
a,so$#te
red#ction
of 1=
7er)
centa*e
7oints in
te ris"
of stro"e
over a
7eriod of
12
!onts-
8
G
S#r*e
ry
res#$t
ed in
a
!ore
!od)
est
,enefi
t
.a,so$
#te
ris"
red#ct
ion of
G-3
7er)
centa
*e
7oints
over a
7eriod
of 3
years/
in 7a)
tients
'it
!oder
ate
stenos
is and
no
,enefi
t in
tose
'it
!i$d
.H3:
4/
ste
nos
is-
8
8(8
3
Ca
ref
#$
at)
ten
tio
n
to
te
res
#$t
s
of
car
oti
d
en
dar
ter
ect
o!
y
in
an
y
*iv
en
cen
ter
is
ess
ent
ia$
to
ens#re tat te
s#r*ica$ ris"s do
not e0ceed tose
in te c$inica$
tria$s-
2
Te ti!in* of
carotid
endarterecto!y
after a TIA or
isce!ic stro"e
invo$ves ,a$ancin*
te ris" of ear$y
rec#rrent events
'it te ris" of
re7erf#)sion in>#ry
and e!orra*ic
transfor!ation-
Ear)$y
intervention(
'itin 5 'ee"s
after te onset of
sy!7to!s( is no'
reco!!ended(
*iven evidence
tat te ,enefits of
s#r*ery ra7id$y
di!inis 'it
increasin* ti!e
since te isce!ic
event-
8=
Te #se of
carotid)artery
stentin* as an
a$ter)native to
carotid
endarterecto!y is
!ore
contro
)
versia$
-
Caroti
d)
artery
stentin
* is
$ess
invasi
ve
tan
endart
erecto
!y
and is
associ
ated
'it a
!ore
ra7id
recove
ry and
a
!#c
$o'er
ris" of
crania$
)nerve
7a$sies
-
%o'e
ver(
st#dies
ave
so'n
tat
te
7eri7r
oced#r
a$
ris"s
.cief$
y
deat
and
rec#r)
rent
stro"e
'itin
6:
days/
are
si*nifi
cant$y
i*er
'it
carotid)
artery
stentin*
tan 'it
carotid
end)
arterecto
!y-
6G)6<
In te
Carotid
Revasc#$
ari9ation
Endartere
cto!y
vers#s
Stentin*
Tria$
.CREST/
( tese
ris"s
'ere
offset ,y
a
red#ce
d rate
of
!yo)
cardia
$
infarct
ion in
te
stentin
*
*ro#7(
s#c
tat
overa$
$
o#tco
!es
.stro"
e(
!yoca
rdia$
in)
farctio
n(
and
dea
t/
'e
re
si!
i$ar
'it

te
t'
o
7ro
ced
#re
s at
6:
day
s
and
at
8
yea
rs-
6<
%o'ever( te
7#r7orted
e+#iva$ence of
tese 7roced#res
as ,een
+#estioned( *iven
tat te $on*er)
ter! ea$t effects
of stro"e o#t'ei*
tose of !yo)
cardia$ infarction-
Data fro! CREST
and E#ro)7ean
stentin* tria$s
indicate tat te
re$ative ,enefits
and ris"s of te
7roced#res vary
accord)in* to a*e-
In 7atients o$der
tan =: years of
a*e( carotid
endarterecto!y
a77ears to ,e
s#7erior to carotid)
artery
stentin
*(
'ere
as in
7atient
s =:
years
of a*e
or
yo#n*
er( te
7eri7r
oced#r
a$
ris"s
of
stro"e
and
deat
are
si!i$ar
'it
te
t'o
7roced
#res(
6<
(8:
and
carotid
)artery
stentin
* .7er)
for!e
d ,y
interve
ntionis
ts 'it
acce7t
a,$e
co!)
7$icati
on
rates/
is a
reason
a,$e
a$terna
tive to
ca)
% 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54 1<1<
The
New
Englan
d Journal of
Medicine
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n
e
j
m
.org on August
8, 2012. For
personal use
only. No other
uses
with
out
perm
issio
n.
Copy
right
© 2012
Massachus
etts
Medical
Society.
All rights
reserved.
T h e NE W ENGL A ND JOUR NA L o f MEDICINE
rotid endarterecto!y- %o'ever( tere are $i!ited St#dies of secondary)7revention strate*ies for
$on*)ter! data re*ardin* te o#tco!es of ca) oter conditions associated 'it an increased ris"
rotid)artery stentin* to *#ide decision !a"in*-
2
of stro"e( inc$#din* aortic)arc atero!a
81
and
intracrania$ aterosc$erosis( are neededE intracra)
ATRIAL FIBRILLATION AND ANTICOAGULATION nia$ aterosc$erosis acco#nts for #7 to 3:4 of
Atria$ fi,ri$$ation ca#ses at $east 134 of cases of isce!ic stro"es in Asian 7o7#$ations-
35
Anti7$ate)
isce!ic stro"e- Dose)ad>#sted 'arfarin as ,een $et tera7y and intensive ris")factor !ana*e!ent
te !ainstay of tera7y- A !eta)ana$ysis of tria$s are reco!!ended for s#c 7atients- A rando!i9ed
co!7arin* 'arfarin 'it 7$ace,o or as7irin so'ed tria$ co!7arin* 'arfarin 'it as7irin in 7atients
red#ctions in te ris" of stro"e of G:4 and 8:4( 'it stro"e or TIA ca#sed ,y intracrania$ stenosis
res7ective$y( a$to#* tese 'ere cief$y 7ri!ary) 'as ter!inated ear$y o'in* to i*er ris"s of ad)
7revention tria$s-
82
Warfarin as a$so ,een so'n verse o#tco!es 'it 'arfarin(
36
and a tria$ co!)
to ,e !ore effective tan as7irin
12
or te co!,i) 7arin* an*io7$asty and stentin* 'it a**ressive
nation of as7irin 7$#s c$o7ido*re$
8<
for secondary !edica$ !ana*e!ent in s#c 7atients 'as a$ted
7revention of stro"e in 7atients 'it atria$ fi,ri$) ,eca#se of increased a9ards 'it stentin*-
85
$ation- Arteria$ dissection is one of te !ost co!!on
Ne'er ora$ anticoa*#$ant strate*ies( 'ic do ca#ses of stro"e in yo#n* ad#$tsE te !ost effec)
not re+#ire !onitorin*( are no' avai$a,$e and are tive tera7y after a dissection re!ains #nc$ear-
38
$i"e$y to re7$ace 'arfarin in !any cases( a$to#* A $ar*e tria$ co!7arin* as7irin and 'arfarin in
tey are !ore cost$y- In a rando!i9ed tria$ of 7a) s#c 7atients is #nder 'ay .NCT::562GG=/-
tients 'it atria$ fi,ri$$ation .5:4 of 'o! ad a
7rior stro"e or TIA/( da,i*atran .a direct tro!) GUIDELINES
,in ini,itor/( at a dose of 13: !* t'ice 7er day(
'as s#7erior to 'arfarin in te 7revention of Te A!erican Stro"e Association and E#ro7ean
stro"e or syste!ic e!,o$is!( 'it a si!i$ar ris" of Stro"e Or*ani9ation ave 7#,$ised *#ide$ines for
overa$$ !a>or ,$eedin* ,#t a si*nificant$y $o'er te 7revention of stro"e in 7atients 'it an ini)
ris" of intracrania$ e!orra*e-
1<
At a $o'er dose tia$ stro"e or TIA-
2(33
O#r reco!!endations are
.11: !* t'ice 7er day/( da,i*atran 'as noninfe) $ar*e$y consistent 'it tese *#ide$ines-
rior to 'arfarin( 'it a $o'er ris" of overa$$ !a>or
,$eedin*- Rando!i9ed tria$s ave a$so so'n te
CONCLUSIONS
efficacy of factor Ia ini,itors in red#cin* stro"e AND RECOMMENDATIONS
ris" a!on* 7atients 'it atria$ fi,ri$$ation- Li"e
da,i*atran( rivaro0a,an 'as noninferior to 'ar) Te 7atient descri,ed in te vi*nette ad an isce
farin( 'it a $o'er ris" of ,$eedin*-
5:
A7i0a,an as !ic stro"e and as a i*)*rade carotid stenosis-
,een so'n to ,e s#7erior to 'arfarin( 'it re) We 'o#$d refer tis 7atient for 7ro!7t carotid
d#ctions in te ris" of ,$eedin* and !orta$ity(
51
endarterecto!y( a$to#* carotid stentin* 'o#$d
and for 7ersons in 'o! 'arfarin as #nacce7t) a$so ,e reasona,$e( *iven er a*e- We 'o#$d rec)
a,$e adverse effects( a7i0a,an as ,een so'n to o!!end contin#in* er statin tera7y( 7rovidin*
,e s#7erior to as7irin-
3:
$o')dose as7irin .e-*-( 21 !* dai$y/( and $o'erin*
er ,$ood 7ress#re- We 'o#$d favor treat!ent
AREAS OF UNCERTAINT J 'it an ACE ini,itor and a di#retic( *iven teir
efficacy in a rando!i9ed secondary)7revention tri)
Patent fora!en ova$e is !ore co!!on in 7atients a$(
16
'i$e reco*ni9in* tat tere is #ncertainty
'it cry7to*enic stro"e tan in te *enera$ 7o7) a,o#t 'ic strate*y is !ost effective- Te 7atient
#$ation( and 7atients 'it ,ot 7atent fora!en so#$d ,e infor!ed a,o#t $ifesty$e factors and te
ova$e and atria$ se7ta$ ane#rys! a77ear to ,e at i!7ortance of avoidin* s!o"in* and o,esity and
increased ris" for stro"e-
31
Anti7$ate$et tera7y is e0ercisin* re*#$ar$y-
*enera$$y reco!!ended for 7atients 'it 7atent
fora!en ova$e after a stro"e or TIA- Te efficacy
Dr- Davis re7orts receivin* cons#$tin* fees fro! &oerin*er
and safety of endovasc#$ar c$os#re for te 7reven) In*e$ei! and $ect#re fees fro! Sanofi)Aventis( and Dr- Donnan
tion of rec#rrent stro"e in s#c 7atients re!ains receivin* cons#$tin* fees fro! &ayer %ea$tCare- No oter 7o)
+#estiona,$eE one recent tria$ so'ed no ,enefit tentia$ conf$ict of interest re$evant to tis artic$e 'as re7orted-
of endovasc#$ar c$os#re-
86
Disc$os#re for!s 7rovided ,y te a#tors are avai$a,$e 'it
te f#$$ te0t of tis artic$e at NEJM-or*-
1<5: % 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54
The New England Journal of Medicine
Downloaded from nejm.org on August 8, 2012. For personal use only. No other uses without permission.
Copyright © 2012 Massachusetts Medical Society. All rights reserved.
CLINICAL PRACTICE
REFERENCES
1. Rot'e$$ PM( Co#$$ AJ(
Si$ver LE( et a$- Po7#$ation)
,ased st#dy of event)rate(
inci)dence( case fata$ity( and
!orta$ity for a$$ ac#te
vasc#$ar events in a$$ arteria$
territo)ries .O0ford ;asc#$ar
St#dy/- Lancet 5::3E
6GGC1==6)26-
2. Stron* A( Maters C(
&onita R- Pre)ventin* stro"eC
savin* $ives aro#nd te 'or$d-
Lancet Ne#ro$ 5::=EGC125)=-
3. Donnan GA( Fiser M(
Mac$eod M( Davis SM- Stro"e-
Lancet 5::2E6=1C1G15)56-
4. Gi$es MF( Rot'e$$ PM-
Ris" of stro"e ear$y after
transient iscae!ic attac"C a
syste!atic revie' and !eta)
ana$ysis- Lan)cet Ne#ro$
5::=EGC1:G6)=5-
5. %ac"a! DG( S7ence JD-
Co!,inin* !#$ti7$e
a77roaces for te secondary
7revention of vasc#$ar events
after stro"eC a +#antitative
!ode$in* st#dy- Stro"e 5::=E
62C1221)3-
6. Easton JD( Saver JL(
A$,ers GW( et a$- Definition
and eva$#ation of transient
isce!ic attac"C a scientific
state!ent for ea$tcare
7rofessiona$s fro! te A!eri)
can %eart
AssociationDA!erican Stro"e
Association Stro"e Co#nci$(
Co#nci$ on Cardiovasc#$ar
S#r*ery and Anestesia(
Co#nci$ on Cardiovasc#$ar
Radio$o*y and Intervention(
Co#nci$ on Cardiovasc#$ar
N#rsin*( and te
Interdisci7$inary Co#nci$ on
Peri7era$ ;asc#$ar DiseaseC
te A!er)ican Acade!y of
Ne#ro$o*y affir!s te va$#e
of tis state!ent as an
ed#cationa$ too$ for
ne#ro$o*ists- Stro"e 5::<E8:C
55=G)<6-
7. Go$dstein L&( Jones MR(
Matcar D&( et a$- I!7rovin*
te re$ia,i$ity of stro"e
s#,*ro#7 c$assification #sin*
te Tria$ of ORG 1:1=5 in
Ac#te Stro"e Treat!ent
.TOAST/ criteria- Stro"e
5::1E65C1:<1)2-
8. F#rie AL( Aasner SE(
Ada!s RJ( et a$- G#ide$ines
for te 7revention of stro"e in
7atients 'it stro"e or
transient isce!ic attac"C a
*#ide$ine for ea$tcare
7rofes)siona$s fro! te
A!erican %eart Associa)
tionDA!erican Stro"e
Association- Stro"e
5:11E85C55=)=G-
9. To'fi*i
A( Mar"ovic
D( Ov,ia*e$e
&- I!7act of a
ea$ty
$ifesty$e on a$$)
ca#se and
cardiovasc#$ar
!orta$ity after
stro"e in te
USA- J Ne#ro$
Ne#ros#r*
Psyciatry
5:15E26C18G)
31-
10. OK
Donne$$ MJ(
Iavier D( Li#
L( et a$- Ris"
factors for
iscae!ic and
intracere),ra$
ae!orra*ic
stro"e in 55
co#ntries .te
INTERSTRO
AE st#dy/C a
case)contro$
st#dy- Lancet
5:1:E6=GC115)
56-
11. PR
OGRESS
Co$$a,orative
Gro#7- Ran)
do!ised tria$
of a
7erindo7ri$)
,ased ,$ood)
7ress#re)
$o'erin*
re*i!en
a!on* G(1:3
individ#a$s
'it 7revio#s
stro"e or tran)
sient
iscae!ic
attac"- Lancet
5::1E632C
1:66)81-
LErrata( Lancet
5::1E632C133G
(
5::5E63<C515:
-M
12. A
!arenco P(
&o*o#ss$avs"y
J( Ca$$a)an A
III( et a$- %i*)
dose
atorvastatin
after stro"e or
transient
isce!ic
attac"- N En*$
J Med
5::GE633C38<)
3<-
13. An
titro!,ot
ic
Tria$istsK
Co$$a,ora)
tion-
Co$$a,orative
!eta)ana$ysis
of ran)
do!ised tria$s
of anti7$ate$et
tera7y for
7revention of
deat(
!yocardia$
infarc)tion(
and stro"e in
i* ris"
7atients- &MJ
5::5E658C=1)
2G-
14. A$
*ra A( van
Gi>n J- As7irin
at any dose
a,ove 6: !*
offers on$y
!odest 7ro)
tection after
cere,ra$
iscae!ia- J
Ne#ro$
Ne#ros#r*
Psyciatry
1<<GEG:C1<=)
<-
15. C
APRIE
Steerin*
Co!!ittee- A
ran)do!ised(
,$inded( tria$
of c$o7ido*re$
ver)s#s as7irin
in 7atients at
ris" of
iscae!ic
events
.CAPRIE/-
Lancet
1<<GE682C165<
)
6<-
16. Di
ener %C(
C#na L(
For,es C(
Sive)ni#s J(
S!ets P(
Lo'enta$ A-
E#ro7ean
Stro"e
Prevention
St#dy- 5-
Di7yrida!o$e
and
acety$sa$icy$ic
acid in te
secondary
7revention of
stro"e- J
Ne#ro$ Sci
1<<GE 186C1)
16-
17. No
rt A!erican
Sy!7to!atic
Carotid
Endarterecto!y
Tria$
Co$$a,orators- &en)eficia$ effect
of carotid endarterecto!y in
sy!7to!atic 7atients 'it i*)
*rade ca)rotid stenosis- N En*$ J
Med 1<<1E653C883)
36-
18. EAFT .E#ro7ean
Atria$ Fi,ri$$ation Tria$/ St#dy
Gro#7- Secondary 7revention
in non)re#!atic atria$
fi,ri$$ation after transient
iscae!ic attac" or !inor
stro"e- Lancet
1<<6E685C1533)G5-
19. Conno$$y SJ(
E9e"o'it9 MD( J#s#f S( et a$-
Da,i*atran vers#s 'arfarin in
7a)tients 'it atria$
fi,ri$$ation- N En*$ J Med
5::<E6G1C116<)31- LErrat#!(
N En*$ J Med
5:1:E6G6C12==-M
20. Pate$ MR(
Maaffey AW( Gar* J( et a$-
Rivaro0a,an vers#s 'arfarin
in nonva$v#)$ar atria$
fi,ri$$ation- N En*$ J Med
5:11E 6G3C226)<1-
21. Gran*er C&(
A$e0ander J%( McM#rray JJ( et
a$- A7i0a,an vers#s 'arfarin in
7a)tients 'it atria$ fi,ri$$ation-
N En*$ J Med 5:11E6G3C<21)<5-
22. Sandset EC( &at
PM( &oysen G( et a$- Te
an*iotensin)rece7tor ,$oc"er
candesar)tan for treat!ent of
ac#te stro"e .SCAST/C a
rando!ised( 7$ace,o)contro$$ed(
do#,$e),$ind tria$- Lancet
5:11E6==C=81)3:-
23. Rasid P(
Leonardi)&ee J( &at P-
&$ood 7ress#re red#ction and
secondary 7revention of
stro"e and oter vasc#$ar
eventsC a syste!atic revie'-
Stro"e 5::6E 68C5=81)2-
24. J#s#f S( S$ei*t P(
Po*#e J( &osc J( Da)vies R(
Da*enais G- Effects of an
an*ioten)sin)convertin*B
en9y!e ini,itor( ra!i7ri$( on
cardiovasc#$ar events in i*)
ris" 7a)tients- N En*$ J Med
5:::E685C183)36- LEr)rata( N
En*$ J Med 5:::E685C=82(
16=G-M
25. T#rn,#$$ F( Nea$
&( Nino!iya T( et a$- Effects
of different re*i!ens to $o'er
,$ood 7ress#re on !a>or
cardiovasc#$ar events in o$der
and yo#n*er ad#$tsC !eta)
ana$ysis of rando!ised tria$s-
&MJ 5::2E 66GC1151)6-
26. Scrader J( LNders
S( A#$sce's"i A( et a$-
Mor,idity and Morta$ity After
Stro"e( E7rosartan Co!7ared
'it Nitrendi7ine
for Secondary
PreventionC
7rinci7a$
res#$ts of a
7ros7ective
rando!i9ed
contro$$ed
st#dy
.MOSES/-
Stro"e
5::3E6GC1512)
5G-
27. J#
s#f S( Diener
%C( Sacco RL(
et a$-
Te$!isartan to
7revent
rec#rrent
stro"e and
cardiovasc#$ar
events- N En*$
J Med 5::2E
63<C1553)6=-
28. Co
$$ins R(
Ar!ita*e J(
Paris S(
S$ei*t P( Peto
R- Effects of
co$estero$)
$o'erin* 'it
si!vastatin on
stro"e and
oter !a>or
vasc#$ar
events in 5:
36G 7eo)7$e
'it
cere,rovasc#$a
r disease or
oter i*)ris"
conditions-
Lancet
5::8E6G6C
=3=)G=-
29. A
!arenco P(
Go$dstein L&(
S9are" M( et
a$- Effects of
intense $o')
density $i7o)
7rotein
co$estero$
red#ction in
7atients 'it
stro"e or
transient
isce!ic
attac"C te
Stro"e
Prevention ,y
A**ressive
Re)d#ction in
Co$estero$
Leve$s
.SPARCL/
tria$- Stro"e
5::=E62C61<2)
5:8-
30. Go
$dstein L&(
A!arenco P(
S9are" M( et
a$-
%e!orra*ic
stro"e in te
Stro"e
Prevention ,y
A**ressive
Red#ction in
Co$estero$
Leve$s st#dy-
Ne#ro$o*y
5::2E
=:C56G8)=:-
31. %
a$"es P%( van
Gi>n J(
Aa77e$$e LJ(
Ao#dstaa$ PJ(
A$*ra A-
Medi#!
intensity ora$
anticoa*#$ant
s vers#s
as7irin after
ce)re,ra$
iscae!ia of
arteria$ ori*in
.ESPRIT/C a
rando!ised
contro$$ed
tria$- Lancet
Ne#ro$
5::=EGC113)
58-
32. S
acco RL(
Diener %C(
J#s#f S( et a$-
As7irin and
e0tended)
re$ease
di7yrida!o$e
vers#s
c$o7ido*re$ for
rec#rrent
stro"e- N En*$
J Med
5::2E63<C1562
)31-
33. D
iener %C(
&o*o#ss$avs"
y J( &rass
LM( et a$-
As7irin and
c$o7ido*re$
co!)7ared
'it
c$o7ido*re$
a$one after
recent
iscae!ic
stro"e or
transient
iscae!ic
attac" in
i*)ris"
7atients
.MATC%/C
ran)do!ised(
do#,$e),$ind(
7$ace,o)
contro$$ed
tria$- Lancet
5::8E6G8C661
)=-
34. &
att DL( Fo0
AA( %ac"e W(
et a$-
C$o7ido*re$
and as7irin
vers#s as7irin
a$one for te
7revention of
aterotro!)
,otic events- N
En*$ J Med
5::GE638C1=:G)
1=-
35. Ae
nnedy J( %i$$
MD(
Ryc",orst AJ(
E$ias9i' M(
De!c#" AM(
&#can AM-
Fast
Assess!ent of
Stro"e and
Transient
Iscae!ic
Attac" to
Prevent Ear$y
Rec#r)rence
.FASTER/C a
rando!ised
contro$$ed
7i$ot tria$-
Lancet Ne#ro$
5::=EGC<G1)<-
36. Ri
n*$e, PA(
A$$en,er* J(
&r#c"!ann %(
et a$- 6: Day
res#$ts fro!
te SPACE
tria$ of stent)
7rotected
an*io7$asty
vers#s carotid
endarterecto!
y in
sy!7to!atic
7a)tientsC a
rando!ised
non)inferiority
tria$- Lancet
5::GE6G2C156<
)8=- LErrat#!(
Lan)cet
5::GE6G2C1562
-M
37. M
as JL(
Cate$$ier G(
&eyssen &( et
a$-
Endarterecto!
y vers#s
stentin* in 7a)
tients 'it
sy!7to!atic
severe carotid
stenosis- N
En*$ J Med
5::GE633C1GG:
)=1-
38. Ed
er$e J( Do,son
J( Featerstone
RL( et a$-
Carotid artery
stentin*
co!7ared 'it
endarterecto!y
in 7atients 'it
sy!7)to!atic
carotid stenosis
.Internationa$
% 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54 1<51
T
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e
New
England
Journal
of
Medicine
Downloaded from
nejm
.org
on
Augus
t 8,
2012.
For personal use
only. No other uses
without permission.
Copyright © 2012
Massachusetts
Medical
Society. All
rights reserved.
CLINICAL PRACTICE
Car
otid
Sten
tin*
St#
dy/C
an
inte
ri!
ana$
y)
sis
of a
rand
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sed
cont
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ed
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-
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5:1
:E6=
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<=-
39
. &
rott
TG(
%o,
son
RW
II(
%o
'ar
d G(
et
a$-
Sten
tin*
vers
#s
end
arte
rect
o!y
for
treat
!en
t of
caro
tid)
arte
ry
sten
osis
- N
En*
$ J
Me
d
5:1
:E6G
6C11
)56-
LErr
ata(
N
En*
$ J
Me
d
5:1
:E6G
6C1<2
(
8<2-M
40.
&ona
ti
L%(
Do,s
on J(
A$*ra
A( et
a$-
Sort
)ter!
o#tco
!e
after
stenti
n*
vers#
s
endar
terect
o!y
for
sy!7
to!at
ic
caroti
d
steno
sisC a
7re7$
anne
d
!eta)
ana$y
sis of
indivi
d#a$
7atie
nt
data-
Lanc
et
5:1:E
6=GC
1:G5)
=6-
41.
Mac$
eod
MR(
A!ar
enco
P(
Davis
SM(
Donn
an
GA-
Ater
o!a
of te
aortic
arcC
an
i!7o
rtant
and
7oor$
y
reco*
nised
fac)
tor in
te
aetio$
o*y
of
stro
"e-
Lan
cet
Ne#
)ro$
5::
8E6C
8:2)
18-
42
. C
i!
o'it
9
MI(
Lyn
n
MJ(
Der
deyn
CP(
et a$-
Sten
tin*
vers
#s
a**r
essi
ve
!ed
ica$
ter
a7y
for
intra
cran
ia$
arter
ia$
sten
osis-
N
En*$
J
Med
5:11
E6G3
C<<6
)
1::
6-
43
. F
#r$a
n
AJ(
Reis
!an
M(
Mas
saro
J( et
a$-
C$os
#re
or
!ed
ica$
ter
a7y
for
cry7
to)
*eni
c
stro
"e
'it
7aten
t
fora
!en
ova$e
- N
En*$
J
Med
5:15E
6GGC<
<1)<-
44.
E#ro
7
e
a
n
C
ar
ot
id
S
#
r
*
er
y
T
ri
a$
is
ts
K
Co$$
a,or
ativ
e
Gro
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MR
C
E#r
o7e
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roti
d
S#r
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Tria
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inte
ri!
res#
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for
sy!
7to
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c
7ati
ents
'it
seve
re
.=:)
<<
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or
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d
.:)
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caro
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osis
-
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45
. R
ot
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PM(
E$ia
s9i
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M(
G#t
ni"o
v
SA(
et
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Ana
$ysi
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7oo$
ed
data
fro
!
te
rand
o!is
ed
contr
o$$ed
tria$s
of
endar
ter)
ecto
!y
for
sy!7
to!at
ic
caroti
d
steno
sis-
Lanc
et
5::6E
6G1C1
:=)
1G-
46.
&arn
ett
%J(
Tay$o
r
DW(
E$ias
9i'
M( et
a$-
&ene
fit of
caroti
d
endar
terect
o!y
in
7atie
nts
'it
sy!7
to!at
ic
!ode
rate
or
sever
e
steno
sis- N
En*$
J
Med
1<<2E
66<C
1813)
53-
47.
Rot
'e$$
PM(
E$ias9
i' M(
G#tni
"ov
SA(
War$o
' CP(
&arne
tt %J-
Endar
terect
o)!y
for
sy!7t
o!a
tic
caro
tid
sten
osis
in
re$at
ion
to
c$ini
ca$
s#,*
ro#7
s
and
ti!i
n*
of
s#r*
ery-
Lan
cet
5::
8E6G
6C<1
3)
58-
48
. %
art
RG(
Pear
ce
LA(
A*#
i$ar
MI-
Me)
ta)
ana$
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antit
ro
!,o
tic
ter
a7y
to
7rev
ent
stro
"e
in
7ati
ents
'o
av
e
non)
va$v
#$ar
atria
$
fi,ri
$$ati
on-
Ann
Inte
rn
Med
5::
=E18
GC23
=)
G=-
49
. C
onn
o$$y
S(
Po*#
e J(
%art
R( et
a$-
C$o7i
do*re
$ 7$#s
as7iri
n
vers#
s ora$
anti)
coa*
#$atio
n for
atria$
fi,ri$$
ation
in te
Atri
a$
fi,ri
$$ati
on
C$o
7ido
*re$
Tria$
'it
Ir,e
sarta
n for
7rev
enti
on
of
;asc
#$ar
Eve
nts
.AC
TI;
E
W/C
a
rand
o!i
sed
cont
ro$$e
d
tri)
a$-
Lan
cet
5::
GE6G
=C1<
:6)
15-
50
. C
onn
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SJ(
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$,oo
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Joyn
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C( et
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A7i
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7ati
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'it
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$
fi,ri$)
$ation-
N
En*$ J
Med
5:11E
6G8C2
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1=-
51.
Mas
JL(
Ar+#i
9an
C(
La!y
C( et
a$-
Re)
c#rre
nt
cere,
rovas
c#$ar
event
s
assoc
iated
'it
7aten
t
fora
!en
ova$e
(
atria$
se7ta$
ane#r
ys!(
or
,ot-
N
En*$
J
Med
5::1E
683C1
=8:)
G-
52.
Won
* LA-
G$o,
a$
,#rde
n of
intrac
ra)
nia$
ater
osc$e
rosis-
Int J
Stro
"e
5::
GE1C
132)
<-
53
. C
i!
o'it
9
MI(
Lyn
n
MJ(
%o
'$et
t)
S!i
t
%(
et
a$-
Co
!7a
riso
n of
'arf
arin
and
as7i
rin
for
sy!
7to
!ati
c
intra
cran
ia$
arter
ia$
sten
osis-
N
En*
$ J
Med
5::
3E63
5C
16:
3)
1G-
54
. G
eor*
iadi
s D(
Arn
o$d
M(
von
&#ed
in)
*en
%C(
et a$-
As7ir
in vs
antic
oa*#$
ation
in
caroti
d
artery
disse
ctionC
a
st#dy
of
5<2
7atie
nts-
Ne#r
o$o*y
5::<E
=5C12
1:)3-
55.
G#id
e$ines
for
!ana
*e!e
nt of
isca
e !ic
stro"
e and
transi
ent
isca
e!ic
attac
"
5::2-
Cere
,rova
sc
Dis
5::2E
53C83
=)
3:=-
Copyri
ght ©
2012
Massa
chuset
ts
Medic
al
Societ
y.
SPECIALTIES AND TOPICS AT NE2M
.
ne7ro$o*y( 7ediatrics( and !any oter !edica$
s7ecia$ties- Tese 7a*es( a$on* 'it co$$ections
of artic$es on c$inica$ and nonc$inica$ to7ics(
content and feat#re recent$y 7#,$ised artic$es
1<55
% 2%G: 3
M2D .66"4/
%23M.;RG
MA< 5=,
4/54
The New
England
Journal of
Medicine
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n
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o
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A
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other
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u
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