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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$$
7atient
sC
,$ood)
7ress#r
e
$o'eri
n*(
co$est
ero$
$o'eri
n*
'it
statins(
and
anti7$a
te$et
tera7
y
.e0ce7
t in
7atient
s in
'o!
anticoa
*#$ant
tera7
y is
indicat
ed/-
Oter
strate*
ies are
s7ecifi
c to
te
ca#se
of
stro"e
.Ta),$e
1/-
BLOO
D-
PRES
SURE
LOWE
RING
&$ood
7ress#r
e is te
!ost
i!7ort
ant
!odifi
a,$e
ris"
factor
in ,ot
7ri!ar
y and
second
ary
7reven)
KEY CLINICAL POINTS
S
E
C
O
N
D
A
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Y
P
R
E
V
E
N
T
I
O
N
A
F
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R
IS
C
HE
MI
C
ST
R
O
KE
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R
TR
A
NS
IE
NT
IS
C
HE
MI
C
AT
TA
C
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% 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54
The New
England
Journal of
Medicine
Downloaded from
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e
j
m.
or
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on
A
ug
us
t
8,
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Copyrigh
t 2012
Massach
usetts
Medi
cal
Socie
ty.
All
rights
reser
ved.
T h e NE W ENGL A ND JOUR NA L o f MEDICINE
tion of stro"e- O,servationa$ st#dies and c$inica$
A tria$s s#77ort ,$ood)7ress#re red#ction for sec)
ondary 7revention in !ost 7atients( re*ard$ess of
te initia$ ,$ood)7ress#re $eve$- Data are $ac"in*
to deter!ine te !ost effective ,$ood)7ress#re
tar*et and e0tent of $o'erin*( and *#ide$ines rec)
o!!end tat treat!ent ,e individ#a$i9ed( ,#t ,en)
efits ave ,een $in"ed to a,so$#te ,$ood)7res)
s#re red#ctions of a77ro0i!ate$y 1:D3 !! %*-
Given data s#**estin* te ris"s of i!!ediate
,$ood)7ress#re $o'erin* after stro"e( ca#tion is
'arranted in te ac#te care settin*-
A syste!atic revie' of tria$s of secondary 7re)
vention after stro"e 'it te #se of a*ents in
vario#s c$asses of antiy7ertensive dr#*s so'ed
red#ctions in a$$ 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#$ts !ay
% 2%G: 3 M2D .66"4/ %23M.;RG MA< 5=, 4/54
The New England Journal of
Medicine
D
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Copyright 2012
Massachusetts
Medical Society.
All rights
reserved.
.
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T!+,e 1.
S#r!#egie%
&- Pr&.e"
Be"e-i# -&r
Se)&"$!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
Downloaded from
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
h
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
o!i
sed
cont
ro$$
ed
tria$
-
Lan
)cet
5:1
:E6=
3C<2
3)
<=-
39
. &
rott
TG(
%o,
son
RW
II(
%o
'ar
d G(
et
a$-
Sten
tin*
vers
#s
end
arte
rect
o!y
for
treat
!en
t of
caro
tid)
arte
ry
sten
osis
- N
En*
$ J
Me
d
5:1
:E6G
6C11
)56-
LErr
ata(
N
En*
$ J
Me
d
5:1
:E6G
6C1<2
(
8<2-M
40.
&ona
ti
L%(
Do,s
on J(
A$*ra
A( et
a$-
Sort
)ter!
o#tco
!e
after
stenti
n*
vers#
s
endar
terect
o!y
for
sy!7
to!at
ic
caroti
d
steno
sisC a
7re7$
anne
d
!eta)
ana$y
sis of
indivi
d#a$
7atie
nt
data-
Lanc
et
5:1:E
6=GC
1:G5)
=6-
41.
Mac$
eod
MR(
A!ar
enco
P(
Davis
SM(
Donn
an
GA-
Ater
o!a
of te
aortic
arcC
an
i!7o
rtant
and
7oor$
y
reco*
nised
fac)
tor in
te
aetio$
o*y
of
stro
"e-
Lan
cet
Ne#
)ro$
5::
8E6C
8:2)
18-
42
. C
i!
o'it
9
MI(
Lyn
n
MJ(
Der
deyn
CP(
et a$-
Sten
tin*
vers
#s
a**r
essi
ve
!ed
ica$
ter
a7y
for
intra
cran
ia$
arter
ia$
sten
osis-
N
En*$
J
Med
5:11
E6G3
C<<6
)
1::
6-
43
. F
#r$a
n
AJ(
Reis
!an
M(
Mas
saro
J( et
a$-
C$os
#re
or
!ed
ica$
ter
a7y
for
cry7
to)
*eni
c
stro
"e
'it
7aten
t
fora
!en
ova$e
- N
En*$
J
Med
5:15E
6GGC<
<1)<-
44.
E#ro
7
e
a
n
C
ar
ot
id
S
#
r
*
er
y
T
ri
a$
is
ts
K
Co$$
a,or
ativ
e
Gro
#7-
MR
C
E#r
o7e
an
Ca)
roti
d
S#r
*ery
Tria
$C
inte
ri!
res#
$ts
for
sy!
7to
!ati
c
7ati
ents
'it
seve
re
.=:)
<<
4/
or
'it
!i$
d
.:)
5<
4/
caro
tid
sten
osis
-
Lan
cet
1<<
1E66
=C15
63)
86-
45
. R
ot
'e$$
PM(
E$ia
s9i
'
M(
G#t
ni"o
v
SA(
et
a$-
Ana
$ysi
s of
7oo$
ed
data
fro
!
te
rand
o!is
ed
contr
o$$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$$
PM(
E$ias9
i' M(
G#tni
"ov
SA(
War$o
' CP(
&arne
tt %J-
Endar
terect
o)!y
for
sy!7t
o!a
tic
caro
tid
sten
osis
in
re$at
ion
to
c$ini
ca$
s#,*
ro#7
s
and
ti!i
n*
of
s#r*
ery-
Lan
cet
5::
8E6G
6C<1
3)
58-
48
. %
art
RG(
Pear
ce
LA(
A*#
i$ar
MI-
Me)
ta)
ana$
ysisC
antit
ro
!,o
tic
ter
a7y
to
7rev
ent
stro
"e
in
7ati
ents
'o
av
e
non)
va$v
#$ar
atria
$
fi,ri
$$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
o$$y
SJ(
Ei"e
$,oo
! J(
Joyn
er
C( et
a$-
A7i
0a,a
n in
7ati
ents
'it
atria
$
fi,ri$)
$ation-
N
En*$ J
Med
5:11E
6G8C2
:G)
1=-
51.
Mas
JL(
Ar+#i
9an
C(
La!y
C( et
a$-
Re)
c#rre
nt
cere,
rovas
c#$ar
event
s
assoc
iated
'it
7aten
t
fora
!en
ova$e
(
atria$
se7ta$
ane#r
ys!(
or
,ot-
N
En*$
J
Med
5::1E
683C1
=8:)
G-
52.
Won
* LA-
G$o,
a$
,#rde
n of
intrac
ra)
nia$
ater
osc$e
rosis-
Int J
Stro
"e
5::
GE1C
132)
<-
53
. C
i!
o'it
9
MI(
Lyn
n
MJ(
%o
'$et
t)
S!i
t
%(
et
a$-
Co
!7a
riso
n of
'arf
arin
and
as7i
rin
for
sy!
7to
!ati
c
intra
cran
ia$
arter
ia$
sten
osis-
N
En*
$ J
Med
5::
3E63
5C
16:
3)
1G-
54
. G
eor*
iadi
s D(
Arn
o$d
M(
von
&#ed
in)
*en
%C(
et a$-
As7ir
in vs
antic
oa*#$
ation
in
caroti
d
artery
disse
ctionC
a
st#dy
of
5<2
7atie
nts-
Ne#r
o$o*y
5::<E
=5C12
1:)3-
55.
G#id
e$ines
for
!ana
*e!e
nt of
isca
e !ic
stro"
e and
transi
ent
isca
e!ic
attac
"
5::2-
Cere
,rova
sc
Dis
5::2E
53C83
=)
3:=-
Copyri
ght
2012
Massa
chuset
ts
Medic
al
Societ
y.
SPECIALTIES AND TOPICS AT NE2M
.
ne7ro$o*y( 7ediatrics( and !any oter !edica$
s7ecia$ties- Tese 7a*es( a$on* 'it co$$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
Downloaded from
n
e
j
m
.
o
r
g

o
n
A
u
g
u
st 8,
2012.
For
personal
use
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No
other
uses
witho
u
t
p
e
r
m
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s
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.

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All
rights
reserv
ed.