REVIEW
Non- i amin K an agonis o al an icoagulan s
and a ial ib illa ion guidelines in p ac ice: ba ie s
o and s a egies o op imal implemen a ion
A. John Camm1*, Faus o J. Pin o2, G aeme J. Hankey3,4, Felici a And eo i5, and
F.D. Richa d Hobbs6on behal o he W i ing Commi ee o he Ac ion o S oke
P e en ion alliance†
1
Depa men o Clinical Ca diology, S Geo ge’s Uni e si y o London, London SW17 0RE, UK;
2
Lisbon Uni e si y Medical School, Lisbon, Po ugal;
3
School o Medicine and
Pha macology, The Uni e si y o Wes e n Aus alia, Nedlands, WA, Aus alia;
4
Depa men o Neu ology, Si Cha les Gai dne Hospi al, Nedlands, WA, Aus alia;
5
Depa men o
Ca dio ascula Science, Ca holic Uni e si y, Rome, I aly; and
6
Nu ield Depa men o P ima y Ca e Heal h Sciences, Uni e si y o Ox o d, Ox o d, UK
Recei ed 16 Janua y 2015; accep ed a e e ision 27 Feb ua y 2015
S oke is a leading cause o mo bidi y and mo ali y wo ldwide. A ial ib illa ion (AF) is an independen isk ac o o s oke, inc easing he isk
i e- old. S okes in pa ien s wi h AF a e mo e likely han o he embolic s okes o be a al o cause se e e disabili y and a e associa ed wi h highe
heal hca e cos s, bu hey a e also p e en able. Cu en guidelines ecommend ha all pa ien s wi h AF who a e a isk o s oke should ecei e
an icoagula ion. Howe e , despi e his guidance, egis y da a indica e ha an icoagula ion is s ill widely unde used. Wi h a ocus on he 2012
upda e o he Eu opean Socie y o Ca diology (ESC) guidelines o he managemen o AF, he Ac ion o S oke P e en ion alliance w i ing
g oup ha e iden i ied key easons o he subop imal implemen a ion o he guidelines a a global, egional, and local le el, wi h an emphasis
on access es ic ions o guideline- ecommended he apies. Following iden i ica ion o hese ba ie s, he g oup has de eloped an expe con-
sensus on s a egies o augmen he implemen a ion o cu en guidelines, including p ac ical, educa ional, and access- ela ed measu es. The po-
en ial impac o heal hca e quali y measu es o s oke p e en ion on guideline implemen a ion is also explo ed. By p o iding p ac ical guidance
on how o imp o e implemen a ion o he ESC guidelines, o egion-speci ic modi ica ions o hese guidelines, he aim is o educe he po en ially
de as a ing impac ha s oke can ha e on pa ien s, hei amilies and hei ca e s.
-----------------------------------------------------------------------------------------------------------------------------------------------------------
Keywo ds A ial ib illa ion †Guidelines †O al an icoagulan s †S oke p e en ion
In oduc ion
In 2012, s oke was es ima ed o ha e con ibu ed o he dea hs o
6.7 million people wo ldwide, accoun ing o nea ly 12% o all
dea hs.
1
S oke causes pe manen disabili y in nea ly 5 million
people each yea .
2
A ial ib illa ion (AF) is a signi ican independen
isk ac o o s oke, associa ed wi h an app oxima ely i e- old
excess in isk, bu is much less well ecognized han, o example,
hype ension, o which he excess s oke isk is h ee- old.
3
In add-
i ion, unlike mos o he ca dio ascula isk ac o s o s oke, he
pi o al F amingham S udy ound an inc ease in a ibu able isk due
o AF om 1.5% in indi iduals aged 50–59 yea s o 23.5% o hose
aged 80–89 yea s.
3
A ial ib illa ion is he mos common sus ained
ca diac a hy hmia and ep esen s a global p oblem (Figu e 1).
4–8
Pa ien s wi h AF a e i e imes mo e likely o ha e a s oke han he
gene al popula ion.
3
A ial ib illa ion- ela ed s okes a e almos
wice as likely o be a al and, in su i o s, cause se e e disabili y, in-
c ease heleng ho hospi als ayanddec ease helikelihoodo pa ien s
e u ning o hei own home, compa ed wi h non-AF- ela ed
s okes.
9,10
A ial ib illa ion- ela ed s okes ha e also been associa ed
wi h signi ican ly highe mean di ec cos s pe pa ien han non-AF-
ela ed s okes.
11
Howe e , AF- ela ed s okes can be p e en ed
and hei impac minimized by e ec i e managemen s a egies includ-
ing inc eased de ec ion o AF, adhe ence o s oke p e en ion guide-
lines and an icoagulan use in a - isk pa ien s. Le a ial appendage
occlusion may also ha e a ole in pa ien s who a e unable o ecei e
long- e m an icoagulan managemen , bu i is no a ecommended
al e na i e o an icoagula ion pe se.
12
*Co esponding au ho . Tel: +44 20 8725 3414; ax: +44 20 8725 3416. E-mail add ess: [email p o ec ed]
†
See appendix o ull lis o au ho s.
&The Au ho 2015. Published by Ox o d Uni e si y P ess on behal o he Eu opean Socie y o Ca diology.
Thisis an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Non-Comme cial License (h p://c ea i ecommons.o g/licenses/by-nc/4.0/),which pe mi s
non-comme cial e-use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. Fo comme cial e-use, please con ac jou nals.pe [email protected]
Eu opace (2015) 17, 1007–1017
doi:10.1093/eu opace/eu 068
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Guidelines ha e an impo an ole in op imizing e idence-based
ca e, imp o ing heal h ou comes o indi iduals and popula ions and
dec easing cos s o heal hca e sys ems. Despi e he isk o s oke in
pa ien s wi h AF, and he a ailabili y o clea global guidelines on he
p e en ion o AF- ela ed s oke since 1999, eal-wo ld da a sugges
ha a la ge p opo ion o pa ien s [38% o hose wi h a CHADS
2
(Conges i ehea ailu e,Hype ension,Age ≥75yea s,Diabe esmel-
li us, p io S oke/ ansien ischaemic a ack (doubled)) sco e o 2 in
he Global An icoagulan Regis y in he FIELD-A ial Fib illa ion
(GARFIELD-AF) Regis y] a e s ill no ecei ing s oke p ophylaxis in
line wi h guideline ecommenda ions.
13
Wi h he inc eased con eni-
ence and imp o ed bene i – isk p o ile o he non- i amin K an agon-
is o alan icoagulan s(NOACs; i a oxaban,dabiga an,apixaban,and
edoxaban), his si ua ion may imp o e.
This consensus documen aims o iden i y ba ie s o guideline im-
plemen a ion wo ldwide and o de ine clea s a egies and p ac ice
models o help o e come hese ba ie s, ocusing on he Eu opean
Socie y o Ca diology (ESC) guidelines o he managemen o AF pub-
lished in EP Eu opace in 2012.
12
A Medline sea ch was pe o med o
iden i y guidelines o s oke p e en ion in pa ien s wi h AF and ba -
ie s o guideline implemen a ion, ocusing on egis y da a bu includ-
ingindi iduals udieswhe e ele an .TheAc ion o S oke P e en ion
alliance w i ing commi ee also p o ided hei own coun y-speci ic
expe iences and, based on he colla ed in o ma ion, iden i ied key ba -
ie s o guideline implemen a ion and de eloped consensus s a egies
o help o e come hese ba ie s.
Guidelines o e iew
A ocusedupda eo he2010ESCguidelines o hemanagemen o AF
was issued in 2012.
12
This was pa ly in esponse o posi i e Phase III
clinical ial da a wi h he NOACs dabiga an, i a oxaban, and
apixaban,
14–16
and hei subsequen app o al o s oke p e en ion
in a - isk pa ien s wi h non- al ula AF. The NOACs ha e shown
equi alen o imp o ede icacycompa edwi hwa a inin andomized
con olled ials,wi ha educ ionin he isko se e ebleedinge en s,in
pa icula in ac anial haemo hage (ICH).
14–17
In addi ion, hey all
o e ixed-dose egimens (wi h some dose educ ions manda ed in
special popula ions, such as pa ien s wi h enal impai men ) ha elim-
ina e he need o he ou ine coagula ion moni o ing associa ed wi h
i amin K an agonis s (VKAs). Edoxaban is cu en ly he only one o
hese NOACs ha is no ye widely app o ed in his indica ion. The
ESC guidelines now ecommend he use o he NOACs in mos
pa ien swi ha CHA
2
DS
2
-VASc [Conges i e hea ailu e/le en icu-
la dys unc ion, Hype ension, Age ≥75 yea s (doubled) Diabe es,
S oke (doubled), Vascula disease, Age 65–74 yea s, Sex ca ego y
( emale)] sco e o ≥1 in p e e ence o VKAs (Figu e 2), al hough in
ce ain pa ien s, e.g. hose wi h se e e enal impai men o unde lying
disease on echoca diog am, VKAs emain p e e ed. An i h ombo ic
ea men is no ecommended in low- isk pa ien s wi h a CHA
2
DS
2
-
VASc sco e o 0.
12
Howe e , he la e g oup ep esen ed only 3–7%
o pa ien s in wo la ge coho s udies,
13,18
indica ing ha he majo i y
o pa ien s wi h AF a e candida es o o al an icoagula ion.
In la ge Phase III s udies, he cu en ly app o ed NOACs showed
simila o imp o ed e icacy compa ed wi h wa a in o he p e en-
ion o p ima y s oke o sys emic embolism.
19–21
Se e al o he
NOACs ha e also demons a ed bene i s in he p e en ion o second-
a y s okes, wi h simila e icacy o wa a in, as well as educing he in-
cidence o ICH.
19–21
The isk o a s oke ecu ence is 2.5- old highe
in pa ien s wi h AF who ha e al eady had a s oke o ansien ischae-
mic a ack.
22
These pa ien s may also be a inc eased isk o alls, ha e
demen ia o ha e limi ed access o in e na ional no malized a io
(INR) moni o ing because o dec eased mobili y, making i p oblema -
ic o ensu e e ec i e VKA he apy.
Uni ed S a es:
2.3 million (2008)
(es ima ed 5.6–>12 million by 2050)
Eu opean Union:
10 million (2011)
Japan:
0.8–2.0 million
(2011)
China:
8 million (2008)
Aus alia:
0.9 million (2011)
India:
1.2 million* (2011)
B azil:
4.8 million (2009)
Figu e 1 Es ima es o he p e alence o AF.
4–8
*Based on da a om a single communi y s udy.
A.J. Camm e al.1008
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In addi ion o inco po a ion o he NOACs in o he ecommenda-
ions, ano he signi ican change o he ESC guidelines was a mo e
away om he use o he CHADS
2
sco e o isk-s a i y pa ien s
wi h AF, in a ou o he CHA
2
DS
2
-VASc sco e. This was based on
e idence ha he CHA
2
DS
2
-VASc sco e could be used o mo e
accu a ely iden i y uly ‘low- isk’ pa ien s, who would no equi e
an i h ombo ic he apy.
12
The 2012 guidelines also ecommend he use o he HAS-BLED
[Hype ension, Abno mal enal/li e unc ion, S oke, Bleeding
his o y o p edisposi ion, Labile INR, Elde ly (e.g. age .65 yea s,
ail y, e c.), D ugs/alcohol use] sco e o assess bleeding isk, bu
highligh ha i should ocus e o s on imp o ing he modi iable
isk ac o s o bleeding and should no be used o exclude pa ien s
om o al an icoagulan he apy.
12
The simul aneous use o old and new guidelines, o o guidelines
issued by di e en o ganiza ions, a ei he a global o egional le el,
can lead o a deg ee o con usion o con adic o y guidance. In addi ion,
ecommenda ions may di e be ween guidelines because o a ia ions
in hepopula ions o which heya ein ended.Howe e , ecommenda-
ions o an i h ombo ic he apy a e, o he mos pa , consis en
be ween he majo guidelines. In 2012, he Ame ican College o
Ches Physicians (ACCP) issued guidelines on an i h ombo ic he apy
o AF, which p o ide simila ecommenda ions o he ESC guidelines
(based onCHADS
2
sco ing o isk assessmen ), including a p e e ence
o NOACso e adjus ed-doseVKAsina - iskpa ien s.
23
Olde guide-
lines, such as hose join ly issued by heAme icanCollegeo Ca diology
(ACC), he Ame ican Hea Associa ion (AHA), and he ESC in 2006,
we e de eloped long be o e he NOACs we e a ailable o clinicians
and, in con as wi h newe guidelines, ecommend ace ylsalicylic acid
(ASA) as an al e na i e o wa a in in pa ien s wi h one mode a e isk
ac o o s oke.
24
Upda ed ACC/AHA guidance, issued in 2014,
ecommends o al an icoagula ion o pa ien s wi h p io s oke/ ansi-
en ischaemic a ack o CHA
2
DS
2
-VASc sco e ≥2, whe eas pa ien s
wi h a sco e o 1 may be gi en o al an icoagula ion, ASA, o no an i h-
ombo ic he apy.
25
In 2013, he Eu opean Hea Rhy hm Associa ion
published a p ac ical guide on he use o NOACs in pa ien s wi h non-
al ula AF
26
based on he 2012 ESC ecommenda ions.
Coun y-speci ic guidelines, such as hose om he Na ional Ins i-
u e o Heal h and Ca e Excellence (NICE) in he UK, ecommend
apixaban, dabiga an, and i a oxaban as op ions o he p e en ion
o s oke o sys emic embolism in pa ien s wi h AF.
27
A ocused
upda e o he Canadian Ca dio ascula Socie y (CCS) A ial Fib illa-
ion Guidelines, published in 2012, ecommends NOACs o e o he
o al an icoagulan s in eligible pa ien s.
28
In he Asia-Paci ic egion,
se e al coun ies ha e coun y-speci ic guidelines o he manage-
men o pa ien s wi h AF bu no all ye inco po a e ecommenda-
ions o he use o NOACs. Howe e , he 2014 Japanese
guidelines la gely suppo he ESC 2012 guidelines, as does a consen-
sus s a emen issued in 2013 by he Asia Paci ic Hea Rhy hm
Socie y on an i h ombo ic he apy in pa ien s wi h non- al ula
AF.
29
In o ma ion p o ided by o he o ganiza ions, such as he
Na ional S oke Associa ion in he UK o he Canadian Agency o
D ugs and Technologies in Heal h, who issue he apeu ic e iews,
may also in luence clinical p ac ice a a na ional le el.
Guideline implemen a ion
and ba ie s o implemen a ion
Bene i s o compliance wi h guidelines
Ac i icismo guidelinesis ha heysome imes elyon e idence ha is
ela i ely weak and/o s udies ha ha e been conduc ed wi h
Val ula AFa
<65 yea s and lone AF (including emales)
O al an icoagulan he apy
NOAC VKA
No an i h ombo ic
he apy
No
No (i.e. non- al ula AF)
01≥2
Yes
Yes
A ial ib illa ion
Assess bleeding isk
(HAS-BLED sco e)
Conside pa ien alues
and p e e ences
Assess isk o s oke
(CHA2DS2-VASc sco e)
Figu e 2 Eu opean Socie y o Ca diology (ESC) guideline ecom-
menda ions o hep e en iono s okeinpa ien swi hAF.
12
An ipla-
ele he apy wi h ASA plus clopidog el, o —less e ec i ely—ASA
only, should be conside ed in pa ien s who e use any o al an icoagu-
lan o canno ole a e an icoagulan s o easons un ela ed o bleed-
ing.I he ea econ aindica ions oo alan icoagula iono an ipla ele
he apy, le a ial appendage occlusion, closu e, o excision may be
conside ed. CHA
2
DS
2
-VASc sco e: u quoise, 0; yellow, 1; ed, ≥2.
Line:solid, bes op ion; dashed, al e na i e op ion.
a
Includes heuma -
ic al ula disease and p os he ic al es. AF, a ial ib illa ion; ASA,
ace ylsalicylic acid; CHA
2
DS
2
-VASc, ESC- ecommended s oke isk
sco e[Conges i ehea ailu e/le en icula dys unc ion,Hype en-
sion, Age ≥75 yea s (doubled) Diabe es, S oke (doubled), Vascula
disease, Age 65–74 yea s, Sex ca ego y ( emale)]; HAS-BLED,
[ESC- ecommended bleeding isk sco e, de ined as Hype ension,
Abno mal enal/li e unc ion, S oke, Bleeding his o y o p edispos-
i ion, Labile INR, Elde ly (e.g. age .65 yea s, ail y, e c.), D ugs/
alcohol use]; NOAC, non- i amin K an agonis o al an icoagulan ;
VKA, i amin K an agonis . F om Camm e al. 2012 ocused upda e
o he ESC Guidelines o he managemen o a ial ib illa ion.
Eu opean Hea Jou nal No 2012, 33(21) 2719–2747. Rep oduced
wi h pe mission o Ox o d Uni e si y P ess (UK) &Eu opean
Socie y o Ca diology, www.esca dio.o g/guidelines
Non-VKA o al an icoagulan s: ba ie s and s a egies 1009
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inconsis en me hodologies. Howe e , he e idence o he use o
NOACs in pa ien s wi h non- al ula AF comes om e y la ge, mul-
icen e, andomized con olled Phase III s udies,
14–16
and he
p ima y ecommenda ions made by he ESC in 2012 on an icoagula-
ion in pa ien s wi h AF gene ally ca ied a high le el (A o B) o e i-
dence.
12
Ne e heless, p ospec i e clinical da a o he NOACs a e
lacking in some speci ic a eas; e.g. a p ospec i e andomized s udy o
i a oxaban o pa ien s wi h AF unde going ca dio e sion has been
published ecen ly,
30
bu a simila ial o apixaban (NCT02100228)
is only jus ge ing unde way, and he e is no such p ospec i e s udy
planned o dabiga an. S udies o add ess o he da a gaps wi h he
NOACs a e ongoing.
Published s udies suppo he bene i s o compliance wi h guideline
ecommenda ions o an icoagula ion in pa ien s wi h AF. A c oss-
sec ional s udy o pa ien s admi ed o he Uni e si y o Maas ich
Medical Cen e be ween 2003 and 2006 ound ha 51% o hose
wi h known AF who we e eligible o o al an icoagula ion did no
ecei e i , and ha imp o ed adhe ence o guidelines could po en ially
ha e p e en ed 22% o subsequen ischaemic s okes.
31
Mo e ecen -
ly, a eal-wo ld coho -based s udy o almos 9000 pa ien s ec ui ed
o e 10 yea s ound low annual a es o s oke o h omboembolism
(0.64%), majo bleeding (1.12%), and dea h (1.08%) among un ea ed
pa ien s classi ied as low isk acco ding o he ESC 2012 guidelines (i.e.
CHA
2
DS
2
-VASc sco e 0).
18
These da a suppo he ESC ecommen-
da ion ha hese pa ien s should no ecei e an i h ombo ic he apy.
Fu he mo e, simula ions o pa ien ou comes om he RE-LY
da abase using ESC- ecommended dabiga an ea men p o ocols
oundasigni ican ne clinicalbene i compa edwi hwa a in,suppo -
ing he ESC ecommenda ions.
32
Compliance wi h guidelines in p ac ice
Regis y da a o e aluable insigh s in o pa e ns o d ug use and can
p o ide a means o acking up ake o guideline ecommenda ions.
Fo example, global da a om he GARFIELD-AF Regis y, collec ed
be ween 2009 and 2011, indica ed ha 27% o all pa ien s wi h AF
we es ill ecei ing ASA he apy,compa ed wi h 60%who ecei ed
o al an icoagula ion (Table 1).
13
Howe e , obse a ional da a
om he Eu opean PREFER AF (PRE en ion oF h omboembolic
e en s—Eu opean Regis y in A ial Fib illa ion) egis y collec ed
be ween 2012 and 2013 sugges ha he in oduc ion o he 2010
ESC guidelines was associa ed wi h a mo e away om he use o
ASA o o al an icoagula ion.
40
O he Eu opean egis y da a show
a ia ion in o al an icoagula ion use depending on when he da a
we e collec ed and om which coun y o coun ies (Table 1).
35–41
Ou side o Eu ope, US egis y da a indica e a low use o o al an icoa-
gula ion ac oss all s oke isk ca ego ies.
43
Da a om he REACH
egis y (REduc ion o A he o h ombosis o Con inued Heal h)
demons a ed he lowe use o o al an icoagula ion in pa ien s wi h
AF ec ui ed om Asia (excluding Japan) compa ed wi h hose
ec ui ed om Japan and non-Asian egions.
45
These di e ences high-
ligh ha o alan icoagulan useisno ye consis en a aglobal,coun y,
o egional le el and may be in luenced by ac o s such as he special y
...............................................................................................................................................................................
Table 1 A ial ib illa ion egis ies and su eys
Regis y o s udy Guidelines Pa ien s wi h
AF, n
Coun y/ egion Da a collec ion, yea OAC use (%)
GARFIELD-AF
13
Mul iple 10 614 Global 2009–2011 60
RE-LY AF
33
Mul iple 15 400 Global 2008–2011 30
GLORIA-AF
34
Mul iple 56 000 Global 2011 onwa ds Awai ing da a
Eu o Hea Su ey on AF
35
ACC/AHA/ESC 2001 and
ACCP 2004
5333 Eu ope 2003–2004 64
AFNET
36
ACC/AHA/ESC 2001 9582 Ge many 2004–2006 71
ATRIUM
37
ACC/AHA/ESC 2001 and
ACCP 2008
3667 Ge many 2009 83
P ospec i e non-in e en ional s udy
38
No speci ied 2753 Ge many 2010 64–73
a
ISAF
39
No speci ied 6036 I aly 2011 46
PREFER AF
42
ESC 2010 7243 Eu ope 2012–2013 82
Re ospec i e, coho s udy
43
ACC/AHA/ESC 2006 and
ACCP 2008
171 393 USA 2003–2007 43
ORBIT-AF
44
ACC/AHA/ESC 2006 and
ACCP 2008
10 098 USA 2010–2011 76
REACH
45
No speci ied 300 Asia (ex. Japan) 2006–2011 36
REACH
45
No speci ied 350 Japan 2006–2011 54
REACH
45
No speci ied 6000 Global (ex. Asia) 2006–2011 55
ACC, Ame ican College o Ca diology; ACCP, Ame ican College o Ches Physicians; AF, a ial ib illa ion; AFNET, Cen al Regis y o he Ge man Compe ence NETwo k on A ial
Fib illa ion; AHA, Ame ican Hea Associa ion; ATRIUM, Ou pa ien Regis y Upon Mo bidi y o A ial Fib illa ion; CHADS
2
, Conges i e hea ailu e, Hype ension, Age ≥75 yea s,
Diabe es melli us, p io S oke/ ansien ischaemic a ack (doubled); ESC, Eu opean Socie y o Ca diology; GARFIELD-AF, Global An icoagulan Regis y in he FIELD; GLORIA-AF,
Global Regis y on Long-Te m O al An i h ombo ic T ea men in Pa ien s wi h A ial Fib illa ion; ISAF, I alian Ne wo k o A ial Fib illa ion Managemen su ey; OAC, o al
an icoagulan ; ORBIT-AF, Ou comes Regis y o Be e In o med T ea men o A ial Fib illa ion; PREFER AF, PRE en ion oF h omboembolic e en s—Eu opean Regis y in A ial
Fib illa ion; REACH, REduc ion o A he o h ombosis o Con inued Heal h; RE-LY AF, Randomized E alua ion o Long- e m an icoagulan The apY.
a
CHADS
2
sco e ≥2 (includes low molecula weigh hepa in).
A.J. Camm e al.1010
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o he physicians en olling pa ien s in o he egis ies and he deg ee o
awa eness o upda ed guidelines.
Pa ien and physician- ela ed ba ie s
Regis ies can also p o ide use ul in o ma ion on he easons o
non-adhe ence o guidelines and iden i y ba ie s o hei adop-
ion. GARFIELD-AF highligh ed ha nea ly hal o pa ien s wi h a
CHADS
2
sco e ≥2 we e no ecei ing VKA he apy because o
physician choice, speci ically because o conce ns o e bleeding
isk, pa ien compliance, unce ain y ega ding guideline ecom-
menda ions, all isk o low isk o s oke.
13
Pa ien ac o s, such
as alcohol misuse, medica ion e usal, unsui able co-medica ion
use, o p e ious bleeding e en s, we e he easons o no ini ia -
ing VKA he apy in ,16% o cases.
13
Simila easons we e gi en
o wa a in discon inua ion in he Ou comes Regis y o Be e
In o med T ea men o A ial Fib illa ion (ORBIT-AF).
46
Simila ly,
in he A ial Fib illa ion Clopidog el T ial wi h I besa an o P e-
en ion o Vascula E en s (ACTIVE) A ial, which en olled
pa ien s who we e conside ed unsui able o VKA he apy, he
p ima y eason o en olmen in he ial (accoun ing o 50%
o pa ien s) was physician judgemen ha a VKA was inapp op i-
a e. Pa ien p e e ence accoun ed o 26% o pa ien s en olled,
and speci ic isk o bleeding o 23% o pa ien s.
47
In he Apix-
aban s. Ace ylsalicylic Acid o P e en S okes in A ial Fib illa ion
Pa ien s Who Ha e Failed o A e Unsui able o Vi amin K An ag-
onis T ea men (AVERROES) s udy, he mos equen easons
o no p esc ibing VKAs we e physician judgemen ha INR mon-
i o ing could no be achie ed a he equisi e equency (43%) and
pa ien p e e ence (37%).
48
The S oke and A ial Fib illa ion Ensemble (SAFE) II s udy ound
ha ha ing a younge gene al p ac i ione and being ollowed up by
a ca diologis we e independen ly associa ed wi h he p esc ip ion
o o al an icoagulan s.
49
The p esence o po en ial con aindica ions,
lack o an indica ion, low compliance, and ea o bleeding we e
easons gi en o non-p esc ip ion.
49
These indings highligh ha
he lack o physician awa eness abou o al an icoagula ion and how
o manage complica ions is a key ba ie o adop ion o guideline-
ecommended he apies. A gene al su ey o Du ch gene al p ac i-
ione s also iden i ied en i onmen al ac o s such as o ganiza ional
cons ain s, lack o ime, and lack o esou ces as p ominen ba ie s
o guideline adhe ence.
50
Fu he mo e, up ake o NOACs may be
limi ed by a physician p e e ence o close INR moni o ing, pa icu-
la ly in elde ly o ail pa ien s.
Ano he ba ie o he adop ion o guidelines a ises when heya e
no conside ed applicable a a coun y le el, possibly because o e-
gional he e ogenei y in pa ien baseline cha ac e is ics (e.g. a high
p opo ion o pa ien s no mee ing he c i e ia o ecommended
ea men s o a pe cep ion ha he s udies unde pinning ecommen-
da ions a e based on non- ep esen a i e popula ions), di e ences in
cu en s anda ds o ca e o cul u al pe cep ions o isk s. bene i o
he in e en ion. Fo example, in some Asian coun ies, such as Japan,
he ecommended a ge INR in pa ien s wi h AF ≥70 yea s o age is
lowe (1.6–2.6) han he ecommended a ge o 2.0–3.0, which is
used mo e widely.
51
Simila ly, a lowe 15 mg once-daily dose o i -
a oxaban (o 10 mg once-daily in pa ien s wi h c ea inine clea ance
30–49 mL/min) was speci ically es ed in Japanese pa ien s.
52
Access o guideline- ecommended
he apies
In some coun ies, p esc ibing o he NOACs is es ic ed a a na ion-
al, egional, o local le el. Fo example, he Na ional Heal h Se ice
o Sco land limi s he p esc ip ion o i a oxaban o pa ien s who
appea complian wi h couma in he apy and ye s ill ha e poo
INR con ol, as well as o hose who a e alle gic o o a e unable o
ole a e couma ins.
53
In he UK, he Depa men o Heal h ollows
he NICE guidelines a he han he ESC guidelines. Howe e , e en
hough he NOACs a e ecommended as a he apeu ic op ion by
NICE, many clinical commissioning g oups o egional p esc ibing
g oups in he UK in e p e his ‘op ion’ as second line, wi h wa a in
compulso y as i s -line he apy.
54,55
In he UK and I eland, pa ien s
who a e close o he hospi al and can a end clinics egula ly o co-
agula ion moni o ing and dose adjus men s a e also mo e likely o
ecei e VKAs han hose who li e u he away. In Eas e n Eu opean
coun ies (e.g. Hunga y), he Na ional Heal h Se ice limi s he p e-
sc ip ion o NOACs o pa ien s who ha e had a p e ious s oke o
pa ien s wi h poo INR con ol on couma in he apy.
56
This es ic-
ion is in place because he i s -line use o he NOACs is conside ed
inancially p ohibi i e.
Res ic ed access can also be a esul o adminis a i e ba ie s. Fo
example, in I aly and Hunga y, a limi ed numbe o specialis s a e
allowed o p esc ibe he NOACs; o inalize he p esc ip ion,
hese specialis s a e equi ed o ill ou an elec onic case
epo o m, con ibu ing o a compulso y na ional su ey (www.
agenzia a maco.go .i ). This is a ime-consuming p ocess and, as
such, he na ional Regula o y Au ho i ies ha e indi ec ly discou aged
ou ine implemen a ion o he ESC guidelines o an i h ombo ic
ea men . The bu eauc a ic si ua ion in I aly is mi o ed in o he
coun ies: in I eland and some pa s o England, jus i ica ion o ms
mus be comple ed o allow physicians o p esc ibe he NOACs
and, in Spain, pa ien s mus ha e an INR ha is eco ded o be ou
o ange h ee imes in a ow be o e a pa ien can be p esc ibed
any o hese d ugs, and his may ake weeks.
Access issues can also a ise when upda es o guidelines a e
delayed. Fo example, he Eu opean S oke O ganisa ion (ESO)
has no upda ed i s guidelines on seconda y s oke p e en ion
since 2008,
57
and so he NOACs a e no included. This in luences
he daily p ac ice o s oke specialis s: in some Eas e n Eu opean
coun ies, o ins ance, physicians ace inancial penal ies o e en
imp isonmen i hey a e no complian wi h he guidelines
ecommended o hei special y, e en i he guidelines a e ou -
da ed and do no e lec he la es clinical ad ances in he ield.
In cases such as hese, p e-exis ing guidelines, hough ele an
when hey we e published, a e hemsel es a ba ie o adop ing
new app oaches o he apies. An upda e o he ESO guidelines
is an icipa ed.
E en i guidelines a e up o da e, i does no necessa ily gua an ee
access o ecommended he apies. Fo example, a g oup o Spanish
medical expe s de eloped a consensus documen in line wi h he
ESC guidelines ha was app o ed by he Spanish Minis y o Heal h
o na ional use.
58
Howe e , access o NOACs is s ill o en es ic ed
by local au ho i ies because wa a in is conside ed o be as e ec i e
as he NOACs and is a low-cos d ug, albei wi h high moni o ing
cos s. The e o e, he newe d ugs a e o en limi ed o pa ien s
Non-VKA o al an icoagulan s: ba ie s and s a egies 1011
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who a e uns able on wa a in o who ha e had an ischaemic s oke
and a e a high isk o ICH.
Financial ba ie s o
guideline- ecommended he apies
One o he majo easons o es ic ed access o new guideline-
ecommended he apies is pe cei ed cos . Res ic ions end o be
made based on a conside a ion o sho - e m budge impac , such
as he lowe acquisi ion cos s o VKAs compa ed wi h he NOACs,
a he han he po en ial longe e m economic impac o e en s
ha migh ha e been p e en ed. Non- i amin K an agonis o al an ic-
oagulan s do no equi e ou ine coagula ion moni o ing, which, in
one US s udy, was shown o cos be ween $291 and $943 annually
pe pa ien .
59
The Na ional Ins i u e o Heal h and Ca e Excellence
has es ima ed he annual cos o INR moni o ing, including anspo
cos s,a £656in he i s yea and£540 he ea e .
60
Longe e m cos
sa ings ela e o he di ec cos s o managing he consequences o
an icoagula ion, which a e summa ized in Table 2. Fo example, con-
side ing ha NOACs educe he isk o ICH by a leas hal compa ed
wi h wa a in, hei use could con ibu e subs an ially o long- e m
cos sa ings (Table 3). A s udy in Denma k published in 1999 es i-
ma ed ha ,a e ICH, he mean o al cos o heal hca eandsocialse -
ices du ing he i s yea was 123 200 DKK o US$22 000.
63
Mo e
ecen ly, a s udy in he USA analysing medicine and pha macy
claims o pa ien s wi h AF es ima ed he mean unadjus ed
all-cause heal h cos s in he yea a e a wa a in claim o be $41
903 o pa ien s wi h a leas one ICH.
64
Despi e his, i is o en di i-
cul in p ac ical e ms o implemen a scheme in which a mo e expen-
si e he apy is paid o om one budge (in his case, d ug cos s) o
p o ide cos sa ings ha ela e o a sepa a e budge (blood es s
and moni o ing).
The lack o moni o ing o he NOACs may also ep esen a inan-
cial ba ie o hei implemen a ion. In some coun ies, p ima y ca e
p ac ices and an icoagula ion clinics ecei e a inancial incen i e o
p o iding VKA moni o ing se ices, which could be conside ed
unde h ea wi h he in oduc iono he NOACs.Howe e , wi h ap-
p op ia e aining o pe sonnel, hese acili ies could be epu posed
o ake on a ole in he ini ia ion and managemen o he NOACs
and managemen o co-mo bidi ies and o p o ide aluable guidance
and eassu ance o pa ien s abou hei an icoagula ion ca e. Indeed,
o e all isk ac o con ol, no limi ed o he use o NOACs, is he
mos impo an he apeu ic in e en ion o pa ien s wi h AF.
Financial ba ie s o app op ia e VKA managemen speci ic o in-
di idual coun ies o egions also exis . In many Eas e n and Cen al
Eu opean coun ies, bo h INR moni o ing and a el cos s ( o blood
sampling) a e co e ed by he heal hca e sys em. Howe e , blood
sampling akes place in la ge cen alized labo a o ies ha a e o en
a long dis ance om whe e he pa ien li es, meaning ha subs an ial
wo k ime is los h ough a elling o and om appoin men s; his
can also ha e a nega i e impac on pa ien compliance.
...............................................................................................................................................................................
Table 2 O e iew o e en cos s. Adap ed om Klein jens e al.
61
E en
a
Acu e (pe e en ) (E) Rehabili a ion
(pe e en )
b
(E)
Long- e m ollow-up
(pe 3 mon hs) (E)
Mino s oke 5946 3204 244
Majo s oke 12 247 17 734 2216
Sys emic embolism 5124 No epo ed No epo ed
Clinically ele an non-majo ex ac anial bleeding e en 23 No epo ed No epo ed
Majo ex ac anial bleeding e en 3510 No epo ed No epo ed
In ac anial bleeding e en
c
7699 17 734 2216
Myoca dial in a c ion 7891 No epo ed No epo ed
a
The ange o e en cos s es ed in sensi i i y analyses was +25% o he mean.
b
Based on unpublished esul s (K. Pu man, pe sonal communica ion).
c
Based on ma ke sha e and p ices o locally a ailable b ands.
...................................................................................................................
..............................................................................................................................................................................
Table 3 Absolu e pe cen age annual isk o ICH s a i ied by s oke isk in pa ien s wi h non- al ula AF ecei ing o al
an icoagula ion he apy o s oke p e en ion. Adap ed om Rognoni e al.
62
In ac anial bleeding, absolu e annual isk (%)
CHADS
2
≤
1 CHADS
2
52 CHADS
2
≥
3
Wa a in 0.48 0.65 1.01
Ri a oxaban (20 mg od) No in es iga ed 0.44 0.68
Apixaban (5 mg bid) 0.2 0.27 0.42
Dabiga an (150 mg bid) 0.2 0.26 0.52
bid, wice daily; CHADS
2
, Conges i e hea ailu e, Hype ension, Age ≥75 yea s, Diabe es melli us, p io S oke/ ansien ischaemic a ack (doubled); od, once daily; ICH,
in ac anial haemo hage.
A.J. Camm e al.1012
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In B azil and many Sou h Eas Asian coun ies, only 30% o pa ien s
ha e p i a e heal h insu ance and, he e o e, ha e access o he
newe he apies o s oke p e en ioninpa ien swi h AF.Incon as ,
pa ien s ea ed in he public sec o ypically con inue o ecei ewa -
a in o ano he VKA because hese d ug cos s a e suppo ed by he
heal hca e sys em. In B azil and Mexico, he local au ho i ies can sub-
sidize mo e expensi e medica ions, bu i akes ime o ge new he -
apies included on hese lis s and, because i is no a na ional
esponsibili y, di e ences in access exis be ween local au ho i ies.
In cos -e ec i eness analyses, he NOACs ha e been shown o be
cos -e ec i e compa ed wi h wa a in.
61,65–74
Robus and well-
designed cos -e ec i eness analyses can be impo an when a guing
he case o conside a ion o new he apeu ic op ions wi h policy
make s. Howe e , hese analyses a e no wi hou limi a ions. Thei
gene al applicabili ycan be limi ed because o di e encesin heal hca e
sys ems be ween coun ies. Fu he mo e, cos -e ec i eness analyses
may be inadequa e because hey do no ake in o conside a ion all
ac o s, pa icula ly indi ec cos s including loss o wo k o pa ien s
o ca e sdue oINRclinic isi sandassocia ed a elcos s.
75
Addi ion-
ally, e en demons a ing he cos -e ec i eness o a d ug wi hin he
pa ame e s de ined in he analysis may no p o ide a compa ison o
cos -e ec i eness ela i e o o he es ablished ea men s.
In addi ion o hei cos -e ec i eness, he ela i e e ec i eness
and sa e y o he NOACs compa ed wi h he VKAs is an impo an
bene i . The con enience o pa ien s in e ms o lack o moni o ing
and die a y es ic ions, which is likely o imp o e pe sis ence and ad-
he ence and he e o e clinical ou comes, should also no be unde -
es ima ed.
Bes p ac ice in Eu opean Socie y
o Ca diology guideline implemen a ion
Regis y da a highligh ha i can ake se e al yea s o guideline
ecommenda ions o be implemen ed in clinical p ac ice, and
e en hen, ecommenda ions may no be applied p ope ly o con-
sis en ly. I is also clea ha he e is wide a ia ion be ween coun-
ies ega ding which ecommenda ions a e implemen ed and how
his is achie ed. When he w i ing commi ee a ed he impo -
ance o ce ain ac o s o guideline implemen a ion, a ia ion
be ween coun ies did exis , bu ac o s such as AF sc eening,
diagnosis, and s oke isk assessmen we e a ed o high impo -
ance ac oss he g oup.
The ba ie s o guideline implemen a ion ha he g oup iden i ied
(summa ized in Table 4) all in o h ee main ca ego ies: p ac ical, edu-
ca ional, and access ela ed. P ac ical issues ela e p ima ily no only
o op imal diagnosis and isk s a i ica ion o pa ien s wi h AF bu also
o he applicabili y o he ESC guidelines o non-Eu opean popula-
ions. Lack o awa eness o he ESC guidelines and delays in
upda es o local o na ional guidelines a e he key educa ional ba -
ie s ha exis , despi e he e o s o he ESC o p omo e i s guide-
lines h ough a ious me hods, including ‘ ain he eache ’
p og ammes, ESC guideline implemen a ion oolki s, and mobile
pocke guidelines. Ano he educa ional ba ie s ems om he
a ie y o in o ma ion a ailable abou he NOACs, which can lead
o con usion o e hei speci ic p ope ies and use p o ocols.
Access- ela ed issues a e p ima ily due o cos and also include
o he ac o s ha ha e been discussed abo e.
In ligh o hese ba ie s, he Ac ion o S oke P e en ion alliance
w i ing commi ee ecommends se e al bes -p ac ice s a egies
(summa ized in Table 5) o imp o e adhe ence o he ESC guidelines
(o hei egion-speci ic modi ica ion) and access o guideline-
ecommended he apies.
Measu ing heal hca e quali y o s oke
p e en ion: po en ial ole in guideline
implemen a ion
Regis ies p o ide in o ma ion on whe he guidelines ha e been
implemen ed. Howe e , could heal hca e quali y measu es be used
o d i e implemen a ion o , and adhe ence o, guidelines as hey
a e issued? Un o una ely, da a on he use o heal hca e quali y mea-
su es o imp o e s oke p e en ion in pa ien s wi h AF a e gene ally
limi ed, al hough na ional audi da a a e a ailable in some coun ies,
highligh ing gaps in ca e o s oke p e en ion.
76,77
In he USA, he e a e se e al ini ia i es aimed a assessing he
quali y o s oke ca e, including he S oke P ac ice Imp o emen
Ne wo k, The Paul Co e dell Na ional Acu e S oke Regis y,
................................................................................
Table 4 Ba ie s o implemen a ion o ESC 2012
guidelines
Ba ie
P ac ical
†Unde -diagnosiso AFbecauseo lacko access o diagnos ic ools o
AF (e.g. Hol e moni o ing)
†No sc eening using he mos e icien echnique, e.g. loop
moni o ing o pa oxysmal AF
†Unde es ima ion o h omboembolic isk
†Applicabili y o ESC guidelines o non-Eu opean popula ions
Educa ional
†Lack o widesp ead awa eness o ESC 2012 Guidelines (coupled wi h
use o o he /p e-exis ing guidelines)
†Delay in upda es o local guidelines o e lec majo en i onmen al
changes o p ac ice
†Fea o majo bleeding/lack o alida ed sco es o e alua e bleeding
isk (HAS-BLED was de eloped based on VKA s udies)
†Lack o echnical expe ise
†De elopmen and a ailabili y o mul iple NOACs in a ela i ely sho
ime ame has led o con usion abou p o ocols o use and he
speci ic p ope ies o each d ug
– Exace ba ed by manu ac u e s p o iding di e en in o ma ion
abou he d ugs in he p esc ibing in o ma ion s. he summa y o
p oduc cha ac e is ics and using di e en ma ke ing app oaches
– In luenced by media epo s, e.g. epo s o se e e bleeding when
dabiga an was i s in oduced
Access
†Budge es ic ions and/o eimbu semen issues wi h NOACs
†Limi a ions/ es ic ions on pa ien s conside ed eligible o NOACs
ha a e inconsis en wi h b oade guideline ecommenda ions
†Limi a ions o p esc ibe eligibili y
†Adminis a i e hu dles associa ed wi h p esc ip ion o NOACs (e.g.
comple ion o pape wo k and jus i ica ion o he clinical decision)
AF, a ial ib illa ion; HAS-BLED, Hype ension, Abno mal li e / enal unc ion,
S oke his o y, Bleeding p edisposi ion, Labile INR, Elde ly (age .65 yea s), D ug/
alcohol use; NOAC, non- i amin K an agonis o al an icoagulan ; VKA, i amin K
an agonis ; INR, in e na ional no malized a io.
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and he ‘Ge wi h he Guidelines’ p og amme. Likewise, in Aus alia,
he na ional p esc ibing se ice MedicineWise is a p og amme ha
aims o imp o e ca dio ascula managemen in p ima y ca e.
Howe e , al hough he use o heal hca e quali y measu es has
shown imp o emen s in ca e and adhe ence o guidelines in
some cases, me hods o implemen ing hese imp o emen s ha e
a ied and he esul s ha e no been consis en .
78–80
In Japan, he
Japanese S oke Da abank is a pa ien o ien ed, academically con-
olled da abase aimed a es ablishing igo ous e idence o he
quali y imp o emen o s oke ca e (h p://c ddb.med.shimane-u.
ac.jp). Physicians egis e da a on hei own academic incen i e
and he da abank is endo sed by he ep esen a i e o s oke
pa ien s, p o iding a success ul collabo a ion be ween pa ien s
and physicians o o e come s oke. In he UK, he Quali y and Ou -
comes F amewo k incen i izes p o ide s o he p o ision o high-
quali y ca e, agains explici clinical indica o s and de ined a ge s,
and helps o s anda dize imp o emen s in he deli e y o p ima y
medical se ices. This sys em is cu en ly being used o imp o e
eco ds o pa ien s wi h AF and hei ongoing managemen and
could be applied o imp o ing he use o NOACs o s oke p e en-
ion in pa ien s wi h AF.
Un il alida ed and s anda dized heal hca e quali y measu es o
s oke p e en ion in pa ien s wi h AF a e de eloped, he ole o
such measu es in d i ing ESC guideline implemen a ion is limi ed.
Howe e , measu es de eloped a a local o hospi al le el could be
o bene i and wa an u he in es iga ion.
...............................................................................................................................................................................
Table 5 Bes -p ac ice s a egies o implemen a ion o he ESC 2012 guidelines and a ionale o such s a egies
S a egy Ra ionale
P ac ical
De elop hospi al and depa men p o ocols and checklis s based on
na ional/local guidelines and implemen quali y indica o s
P o ides clinical p ac ical guidance o day- o-day managemen o
pa ien s wi h AF and allows measu emen o guideline adhe ence
Regula mul idisciplina y eam mee ings and local quali y audi s Allows assessmen o indi idual pa ien s and can ac as an in e nal check
o ensu e hey a e being managed in line wi h guideline
ecommenda ions
Enhances pee - o-pee lea ning expe ience
Plan ollow-up isi s and labo a o y check-ups Ensu es pa ien s a e complian wi h guideline- ecommended he apy
and educes he isk o complica ions
P o ide clea p ac ical guidance on he use o NOACs P o ides eassu ance o physicians no expe ienced in he use o hese
d ugs
Implemen CHA
2
DS
2
-VASc and bleeding isk checklis s be o e p esc ibing
NOACs and a e e y ollow-up isi
Ensu esiden i ica iono pa ien ssui able o an i h ombo ic he apyand
hose a inc eased isk o bleeding
Implemen compliance checks, e.g. speci ic ques ions, pill ‘coun ing’, dia y
comple ion, SMS messages o ala m calls o ake able s
Ensu es pa ien s a e complian wi h guideline- ecommended he apy,
imp o es adhe ence and educes he isk o complica ions
Educa ional
Regula ly dissemina e ESC/na ional and local guideline in o ma ion and upda es Raises awa eness o guidelines
De elop imely coun y-speci ic/local guidelines based on he ESC
ecommenda ions
Allows ecogni ion o coun y-speci ic equi emen s, such as access, so
ha guidelines a e compa ible wi h local condi ions
Re- ain/educa e nu ses cu en ly in ol ed in an icoagula ion/wa a in clinics
o ake on a mo e gene al ole in ini ia ion and managemen o NOACs
Can p o ide an es ablished poin o con ac h ough which pa ien s can
ecei e ad ice on an icoagula ion wi h he NOACs
De elop simple algo i hms o speci ic popula ions o pa ien s wi h AF, as pe
Figu e 2(e.g. pos -ischaemic s oke, pos -haemo hagic s oke, ge ia ic
pa ien s)
P o ides guidance on when and how o s a NOACsand o how long in
hese pa ien s
In o m physicians on how o educa e pa ien s on he impo ance o adhe ence
o he apy
Limi s he likelihood o non-adhe ence o guideline- ecommended
p o ocols
Access
App oach he esponsible pe son wi hin you heal hca e sys em o:
Highligh o key a ge g oups (e.g. budge holde s, policy make s, o mula y
ga e keepe s, he media, pa ien g oups) he po en ial impac o no
p o iding access o guideline- ecommended he apies, om bo h inancial
and clinical pe spec i es
Raises awa eness ha AF is a signi ican isk ac o o s oke and ha
AF- ela ed s oke is p e en able
Pe o m coun y-speci ic cos -e ec i eness analyses o he NOACs
Educa e paye s/budge holde s abou be e u iliza ion o an icoagulan s,
including NOACs, highligh ing po en ial long- e m cos bene i s
P o ides paye s/budge holde s wi h mo e obus e idence o conside
he use o he NOACs as i s -line he apy
–
In o m poli icians, pa ien g oups and he media abou di e ences in access
o AF s oke p e en ion ea men wi hin egions o coun ies
Lobby pa liamen a y and heal hca e bodies o equali y o access
o guideline- ecommended he apies globally o ac oss egions
Pu s p essu e on policy make s o p o ide equali y o ca e o s oke
p e en ion in pa ien s wi h AF wi h ega ds o medica ion
AF,a ial ib illa ion; CHA
2
DS
2
-VASc, Conges i e hea ailu e/le en icula dys unc ion, Hype ension, Age ≥75 yea s (doubled), Diabe es, S oke (doubled), Vascula disease, Age
65–74 yea s, Sex ca ego y ( emale); NOAC, non- i amin K an agonis o al an icoagulan ; SMS, sho message se ice; ESC, Eu opean Socie y o Ca diology.
A.J. Camm e al.1014
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Limi a ions o hese
ecommenda ions
I should be no ed ha , al hough he majo i y o he e idence ci ed in
his documen comes om published clinical s udies o eal-wo ld
in es iga ions, some o he coun y-speci ic in o ma ion, and he ba -
ie s iden i ied as a esul , a e based on pe sonal e idence p o ided
by w i ing commi ee membe s. The ecommenda ions p o ided e-
p esen he opinion o he g oup, and would equi e p ac ical imple-
men a ion o es hei obus ness and applicabili y o di e en
heal hca escena ios. As no ed abo e, he lacko ce ain s anda dized
s uc u es may p e en some ecommenda ions om being imple-
men ed in p ac ice a his ime.
Conclusions
A ial ib illa ion- ela ed s oke is po en ially p e en able and,
h ough be e implemen a ion o he 2012 ESC guidelines, i s
impac on pa ien s, hei amilies, and ca e s, and heal hca e
sys ems can be educed. Howe e , his canno be achie ed wi hou
inc eased de ec ion o pa ien s wi h AF and he inc eased use o
an icoagula ion in hose assessed o be a mode a e o high s oke
isk, using ei he well-con olled wa a in o , p e e ably, NOACs.
P o iding pa ien s wi h a choice o he apy and allowing physicians
o p esc ibe he mos app op ia e an icoagulan o hei pa ien s
will only be possible i he e is access o all guideline- ecommended
he apies. In ou lining p ac ical measu es ha physicians and medical
heal h socie ies wo king in his ieldcan ins iga e o imp o e guideline
implemen a ion, we belie e ha subs an ial bene i s, in e ms o
imp o ed pa ien ou comes and educed heal hca e bu den, can
be achie ed.
Acknowledgemen s
The au ho s would like o acknowledge Sa ah A kinson, who p o-
ided edi o ial suppo o his manusc ip .
Funding
This wo k was suppo ed by edi o ial suppo unded by Baye Heal h-
Ca e Pha maceu icals and Janssen Scien i ic A ai s, LLC. The sponso s
p o ided sugges ions and commen s, bu he con en o his documen
ep esen s he wo k o he au ho s.
Con lic o in e es : A.J.C.: Speake /consul ing ees om Sano i, Baye ,
Daiichi Sankyo, Boeh inge Ingelheim, P ize , and B is ol-Mye s Squibb.
F.J.P.: Speake /consul ing ees om As aZeneca, Baye , and Boeh inge
Ingelheim. G.J.H.: Speake ees om Baye . F.A.: Speake /consul ing
ees om Amgen, Baye , B is ol-Mye s Squibb/P ize , Boeh inge Ingel-
heim, Daiichi Sankyo, and Eli-Lilly. F.D.R.H.: Speake /consul ing ees
om B is ol-Mye s Squibb/P ize , Baye , and Boeh inge Ingelheim;
g an s/sponso ship om Baye and Daiichi Sankyo. La
´szlo
´Csiba:
Speake /consul ing ees om Baye , Boeh inge Ingelheim, MSD,
sano i-a en is, and Egis. Gab iel R. de F ei as: Speake ees om Baye
and Boeh inge Ingelheim. Shinya Go o: Hono a ia om Eisai,
sano i-a en is, O suka, Baye , No a is, As aZeneca, As ellas, P ize ,
Med onics-Japan, Tanabe-Mi subishi, Takeda, Daiichi Sankyo, Mochida,
and MSD. We ne Hacke: Speake /consul ing ees om Baye and
Daiichi Sankyo. Lo enzo Man o ani: Consul ing ees om Baye ; g an s
om Boeh inge Ingelheim, P ize , B is ol-Mye s Squibb, and Daiichi
Sankyo.
ASP W i ing Commi ee Membe s
A. John Camm, Faus o J. Pin o, G aeme J. Hankey, Felici a And eo i, F.D.
Richa d Hobbs, La
´szlo
´Csiba, Gab iel R. de F ei as, Shinya Go o, Ca los
Can u
´, Jo ge Gonzalez-Zuelga ay, We ne Hacke, Han Hwa Hu,
Lo enzo Man o ani, Byung-Woo Yoon, Dayi Hu, and Kui-Hian Sim.
Re e ences
1. Wo ld Heal h O ganiza ion. The op 10 causes o dea h (Fac shee no 310). 2014.
h p://www.who.in /mediacen e/ ac shee s/ s310/en/index.h ml (6 Janua y 2015,
da e las accessed).
2. Wo ld Hea Fede a ion. The global bu den o s oke. 2014. h p://www.
wo ld-hea - ede a ion.o g/ca dio ascula -heal h/s oke/ (6 Janua y 2015, da e
las accessed).
3. Wol PA, Abbo RD, Kannel WB. A ial ib illa ion as an independen isk ac o o
s oke: he F amingham S udy. S oke 1991;22:983–8.
4. Kannel WB, Benjamin EJ. S a us o he epidemiology o a ial ib illa ion. Med Clin
No h Am 2008;92:17–40, ix.
5. S e ansdo i H, Aspelund T, Gudnason V, A na DO. T ends in he incidence and
p e alence o a ial ib illa ion in Iceland and u u e p ojec ions. Eu opace 2011;13:
1110–7.
6. Lloyd-Jones D, Adams RJ, B own TM, Ca ne hon M, Dai S, De Simone G e al. Hea
disease and s oke s a is ics - 2010 upda e: a epo om he Ame ican Hea Asso-
cia ion. Ci cula ion 2010;121:e46–e215.
7. Hu D, Sun Y. Epidemiology, isk ac o s o s oke, and managemen o a ial ib illa-
ion in China. J Am Coll Ca diol 2008;52:865–8.
8. Lip GYH, B echin CM, Lane DA. The global bu den o a ial ib illa ion and s oke: a
sys ema ic e iew o he epidemiology o a ial ib illa ion in egions ou side No h
Ame ica and Eu ope. Ches 2012;142:1489–98.
9. Jø gensen HS, NakayamaH, Rei h J, Raaschou HO, Olsen TS. Acu e s oke wi h a ial
ib illa ion. The Copenhagen S oke S udy. S oke 1996;27:1765–9.
10. Lin HJ, Wol PA, Kelly-Hayes M, Beise AS, Kase CS, Benjamin EJ e al. S oke se e i y
in a ial ib illa ion. The F amingham S udy. S oke 1996;27:1760–4.
11. B u¨ggenju¨ gen B, Rossnagel K, Roll S, Ande sson FL, Selim D, Mu¨lle -No dho n J
e al. The impac o a ial ib illa ion on he cos o s oke: he Be lin Acu e S oke
S udy. Value Heal h 2007;10:137–43.
12. Camm AJ, Lip GY, De Ca e ina R, Sa elie a I, A a D, Hohnlose SH e al. 2012
ocused upda e o he ESC Guidelines o he managemen o a ial ib illa ion: an
upda e o he 2010 ESC Guidelines o he managemen o a ial ib illa ion. De el-
oped wi h he special con ibu ion o he Eu opean Hea Rhy hm Associa ion. Eu o-
pace 2012;14:1385–413.
13. Kakka AK, Muelle I, Bassand JP, Fi zmau ice DA, Goldhabe SZ, Go o S e al. Risk
p o iles and an i h ombo ic ea men o pa ien s newly diagnosed wi h a ial ib il-
la ion a isk o s oke: pe spec i es om he in e na ional, obse a ional, p ospec -
i e GARFIELD Regis y. PLoS One 2013;8:e63479.
14. Pa el MR, Maha ey KW, Ga g J, Pan G, Singe DE, Hacke W e al. Ri a oxaban e sus
wa a in in non al ula a ial ib illa ion. N Engl J Med 2011;365:883–91.
15. G ange CB, Alexande JH, McMu ay JJ, Lopes RD, Hylek EM, Hanna M e al. Apix-
aban e sus wa a in in pa ien s wi h a ial ib illa ion. N Engl J Med 2011;365:
981–92.
16. Connolly SJ, Ezekowi z MD, Yusu S, Eikelboom J, Oldg en J, Pa ekh A e al. Dabiga-
an e sus wa a in in pa ien s wi h a ial ib illa ion. N Engl J Med 2009;361:
1139–51.
17. Giugliano RP, Ru CT, B aunwald E, Mu phy SA, Wi io SD, Halpe in JL e al. Edox-
aban e sus wa a in in pa ien s wi h a ial ib illa ion. N Engl J Med 2013;369:
2093–104.
18. Taillandie S, Olesen JB, Cle
´men y N, Lag enade I, Babu y D, Lip GYH e al. P ognosis
in pa ien s wi h a ial ib illa ion and CHA(2)DS(2)-VASc sco e ¼0 in a communi y-
based coho s udy. J Ca dio asc Elec ophysiol 2012;23:708–13.
19. Hankey GJ, Pa el MR, S e ens SR, Becke RC, B ei ha d G, Ca olei A e al. Ri a ox-
aban compa ed wi h wa a in in pa ien s wi h a ial ib illa ion and p e ious s oke o
ansien ischaemic a ack: a subg oup analysis o ROCKET AF. Lance Neu ol 2012;
11:315–22.
20. Diene HC, Connolly SJ, Ezekowi z MD, Wallen in L, Reilly PA, Yang S e al. Dabiga-
an compa ed wi h wa a in in pa ien s wi h a ial ib illa ion and p e ious ansien
ischaemic a ack o s oke: a subg oup analysis o he RE-LY ial. Lance Neu ol 2010;
9:1157–63.
21. Eas on JD, Lopes RD, Bahi MC, Wojdyla DM, G ange CB, Wallen in L e al. Apix-
aban compa ed wi h wa a in in pa ien s wi h a ial ib illa ion and p e ious s oke o
Non-VKA o al an icoagulan s: ba ie s and s a egies 1015
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