Академический Документы
Профессиональный Документы
Культура Документы
2011.
Measurements: Risk for cardiac death or rehospitalization for
Ml within 60 days of hospitalization.
2015.
M ethods
D esig n O verview
W e conducted a retrospective cohort study o f all
patients hospitalized fo r a first ACS from 1 January
2005 th ro ug h 31 D ecem ber 2011 in Denmark. Patientand hospital-level data were collected from the na
tional Danish registries, which hold inform ation on all
5.6 m illion inhabitants. We studied th e effects o f an
early invasive trea tm en t strategy on adverse cardiac
outcom es in a real-world setting. An early invasive
treatm ent strategy was defined as diagnostic coronary
a ngiography w ithin 72 hours o f the index hospitaliza
tion, assuming cardiac catheterization w ith intent to
perform revascularization if app ro priate on the basis of
See also:
Celebrating the ACP Centennial: From the Annals
A rch ive ......................................................................798
Editorial c o m m e n t...................................................799
2015 American College of Physicians 737
O riginal R esearch
EDITORS'NOTES________________________________________
Context
Setting
The national setup fo r invasive m anagem ent o f pa
tients presenting with an ACS is highly centralized, with
5 invasive heart centers located in densely populated
urban areas and 8 sm aller hospital units perform ing all
acute and subacute cardiac procedures, respectively.
Invasive heart centers are high-volum e hospitals with
facilities fo r cardiac catheterization, percutaneous coro
nary intervention (PCI), and coronary artery bypass
g rafting (CABG). A lthough the smaller hospital units
prim arily perform subacute cardiac catheterizations,
one unit initiated PCI treatm ent o f stabilized patients
with ACSs with low-risk lesions during the study. Emer
gency m edical services perform extensive prehospital
tria g in g using e lectrocardiographic telem edicine, thus
ensuring that patients presenting with ST-segment ele
vation Ml (STEMI) are transported directly to the near
est invasive heart center. Patients with NSTE-ACSs are
a dm itted to the nearest hospital fo r noninvasive phar
m acologic therapy and transferred fo r further invasive
738 Annals of Internal Medicine Vol. 163 No. 10 17 November 2015
Data Sources
W e perform ed individual-level linkage o f data from
5 registries by using the unique personal civil registra
tion num ber given to all Danish citizens at birth or im
m igration. W e identified the study co ho rt from the Dan
ish National Patient Register (9). All hospitals are
required to rep ort inform ation on each hospitalization,
including 1 prim ary discharge diagnosis and, if a p p ro
priate, 1 or more secondary diagnoses coded accord
ing to the International Classification o f Diseases, Eight
Revision, until 1994 and International Classification of
Diseases, 10th Revision (ICD-10) thereafter. The p ri
mary diagnosis is assigned by the treating physician at
discharge and describes the prim ary reason fo r inhospital diagnostic investigation and treatm ent; sec
ondary diagnoses describe additional com orbidity. We
obtained inform ation on cardiac catheterizations, PCIs,
and CABG from the Danish Heart Registry, a clinical
register with m andatory reporting o f data on the tim e,
type, and findings o f all cardiac procedures perform ed
since 2000 (10). The Danish Register o f M edicinal Prod
uct Statistics holds inform ation on all redeem ed drug
prescriptions (grouped according to Anatom ical Ther
apeutic Chemical classification) since 1995. Because
the Danish health care system provides partial reim
bursem ent fo r drug expenses, accurate registration by
pharmacies o f inform ation on all redeem ed prescrip
tions, including dispensing date, drug, quantity, and
strength, is required (11). Deaths and related causes
were obtained from the Danish Register o f Causes of
Death (12). Finally, patient-level data on d em ographic
and socioeconom ic characteristics were p rovided by
Statistics Denmark.
Case Definition
Cases o f ACS were identified by using prim ary d i
agnoses o f Ml (ICD-10 codes 121 to 121.9) and unstable
angina pectoris (UAP) (ICD-10 code I20.0). The d ia g n o
sis o f Ml has been validated, w ith a sensitivity and pos
itive predictive value exceeding 93% and 91%, respec
tively (13). The diagnosis o f UAP has been validated
only by using a strict d efinition requiring e lectrocardio
graphic changes in addition to classic sym ptom s, with a
positive predictive value around 42% (14).
Study Cohort
All patients adm itted to a Danish hospital with
acute Ml (AMI) or UAP were e lig ib le fo r inclusion. We
excluded patients with a p rio r hospitalization fo r an
ACS after 1978 to corroborate the validity o f the d ia g
noses. Patients discharged on the day o f admission
were excluded to ensure sufficient tim e fo r p ro p e r in
vestigations, including e lectrocardiographic m o n ito r
ing and sequential measurements o f cardiac troponins,
to m inimize misclassification due to invalid ACS reco rd
ings. W e restricted the study cohort to patients aged 30
to 90 years under the assum ption that those younger
than 30 years tended to have an underlying cause
www.annals.org
O riginal R esearch
o t h e r th a n a th e r o s c le r o s is a n d m o s t o f th o s e o ld e r th a n
9 0 y e a r s w e r e t o o f r a i l t o h a v e in v a s iv e p r o c e d u r e s .
We
used
a v e r s io n
o f th e
O n ta r io
AMI
m o r t a lit y
p r e d ic t iv e r u le m o d if ie d t o t h e IC D - 1 0 s y s te m t o id e n
t if y c a r d ia c a n d n o n c a r d ia c c o m o r b id it ie s (1 7 , 1 8 ). A d
d it io n a l c h r o n ic c o m o r b id it y w ith p o t e n t ia l in f lu e n c e o n
W e d e f i n e d a n e a r ly in v a s iv e s t r a t e g y a s r e c e i p t o f
tre a tm e n t a n d
o u tc o m e s w a s id e n t if ie d t o
fu rth e r e n
d ia g n o s t ic c o r o n a r y a n g io g r a p h y w ith in 7 2 h o u rs o f t h e
h a n c e p r e d ic t iv e c a p a b ilit ie s . O f n o te , th e IC D - 1 0 s y s
i n d e x h o s p i t a l i z a t i o n . T h is d e f i n i t i o n w a s in a c c o r d a n c e
te m
w ith t h e E u r o p e a n S o c ie ty o f C a r d io lo g y g u id e lin e s f o r
( 1 9 ) . T y p e 2 M l is a s p e c i a l c a s e in w h i c h a n i m b a l a n c e
does
n o t r e fle c t th e
u n iv e r s a l c l a s s i f i c a t i o n
of Ml
N S T E - A C S s a n d t h e t i m e f r a m e s e t b y t h e D a n is h f a s t -
b e tw e e n s u p p ly a n d d e m a n d o f m y o c a r d ia l o x y g e n r e
tr a c k p r o t o c o ls (1 5 , 1 6 ). A
s u lt s in m y o c a r d i a l d a m a g e . T h e p r e v a l e n c e o f t y p e 2
c o n s e r v a tiv e
in v a s iv e s t r a t
e g y w a s d e f in e d a s r e c e ip t o f a n a n g io g r a p h ic a s s e s s
M l in
m e n t a t le a s t 7 2 h o u r s a f t e r t h e i n d e x h o s p i t a l i z a t i o n o r
2 6 % , a n d it is a s s o c i a t e d w i t h l o w u s e o f c a r d ia c c a t h e
n o c a r d i a c c a t h e t e r i z a t i o n . W e f u r t h e r c h a r a c t e r iz e d t h e
t e r i z a t i o n a n d h ig h m o r t a l i t y c o m p a r e d w i t h M l d u e t o
in v a s iv e
tre a tm e n t
subsequent
b o th ),
by
r e v a s c u l a r i z a t io n
le n g t h
h o s p it a l s ,
s tra te g y
o f th e
and
th e ra p y
h o s p it a l
subsequent
u s in g
u n s e le c t e d
p a tie n ts w ith
M l m a y b e a s h ig h
as
in f o r m a tio n
on
c o r o n a r y a r t e r y d is e a s e ( 2 0 , 2 1 ) . P a t ie n t s w i t h t y p e 2 M l
(P C I, C A B G ,
or
c o m m o n l y r e c e iv e s e c o n d a r y d i a g n o s e s o f c a r d ia c a r
s ta y , t r a n s f e r s
b e tw e e n
r h y t h m ia ,
h e a rt
d u a l- a n t ip la t e le t
th e r a p y .
b le e d in g ,
r e n a l in s u ffic ie n c y , c h r o n ic
f a i lu r e ,
s e v e re
in f e c tio n ,
a n e m ia
o b s t r u c t iv e
or
p u l
W e c a l c u l a t e d t h e l e n g t h o f t h e h o s p i t a l s ta y b y a p p l y
m o n a ry
i n g a n a l g o r i t h m t h a t c o m b i n e d u n i q u e h o s p it a l c o d e s ,
r e s p ir a to r y in s u ffic ie n c y (2 2 ). W e t h e r e f o r e in c lu d e d in
d a t e s o f h o s p i t a l i z a t i o n , a n d d a t e s o f d is c h a r g e i n t o
fo r m a t io n o n th e s e in d ic a to r s t o a d d r e s s t h e p o t e n t ia lly
d a te s
s t r o n g c o n f o u n d i n g e f f e c t o f t y p e 2 M l. In t h e a b s e n c e
to ta l
in d e x
h o s p it a liz a tio n ,
p r o v id e d
o v e r la p p e d . T h e s a m e a lg o r it h m
as
th e
w a s u s e d to
th a t
id e n t if y
p o s td is c h a r g e
r e d e m p t io n
of a
use
p re
o f c o re
e re d
d is e a s e
(C O P D ),
c e r e b r o v a s c u la r
c lin ic a l v a r ia b le s , d r u g
a p r o x y f o r id e n t if ie d
e x p o s u re
c a r d ia c
u s e o f a n tih y p e r t e n s iv e m e d ic a t io n
d is e a s e ,
or
w a s c o n s id
r is k f a c t o r s . T h u s ,
in d ic a t e d a h is to r y
s c r ip t io n f o r a s p ir in a n d a n a d e n o s in e d ip h o s p h a t e r e
of
c e p t o r in h ib it o r ( c lo p id o g r e l, t ic a g r e lo r , o r p r a s u g r e l)
d r u g s i n d i c a t e d t h e p r e s e n c e o f d i a b e t e s m e l l it u s , a n d
w i t h i n 6 0 d a y s o f h o s p i t a l i z a t i o n o r p o s s e s s io n o f a s u f
use
f ic ie n t q u a n tity o f m e d ic a tio n
h y p e r c h o le s te r o le m ia .
b e f o r e h o s p it a liz a tio n t o
c o v e r th e e n tir e f o llo w - u p .
h y p e r te n s io n ,
d e fin e d
a d v e r s e c a r d i a c o u t c o m e s a s c a r d ia c
C a r d ia c
d e a th
w as
d e fin e d
a s a p r im a r y
c a r d i a c c a u s e o f d e a t h ( I C D - 1 0 c o d e I 0 0 - 2 5 , I2 7 , o r 130S I ) as a s s e s s e d b y th e tr e a tin g
p it a liz a tio n s
w ith
p r im a r y
i n s u lin
d ru g s
or
g lu c o s e - lo w e r in g
s u g g e s te d
h is to r y
H o s p ita l- le v e l d a ta w e r e g e n e r a t e d fr o m
d e a th o r r e h o s p ita liz a t io n f o r M l w it h in 6 0 d a y s o f h o s
p it a liz a tio n .
lip id - lo w e r in g
of
of
of
use
p h y s ic ia n . O n ly r e h o s
d ia g n o s is
of
Ml
(IC D -1 0
th e
d a ta
a t h a n d , in c lu d in g th e a n n u a l n u m b e r o f A C S h o s p it a l
iz a t io n s a n d a v a i l a b i l i t y o f P C I a n d C A B G f a c i li t i e s . T h e
h o s p it a l v o lu m e
o f p a tie n ts w ith
A C S s c o r r e la te s w e ll
w i t h o t h e r h o s p it a l c h a r a c t e r is t ic s , s u c h a s t h e n u m b e r
o f b e d s a n d th e p r e s e n c e o f c o r o n a r y c a re u n its (2 3 ).
S tatistical A n alysis
c o d e 121 x ) a n d a l e n g t h o f s ta y o f a t le a s t 2 d a y s w e r e
C o n t in u o u s a n d d is c r e t e d a ta a re p r e s e n te d as m e
c o u n t e d a s o u t c o m e s t o e x c lu d e p o t e n t ia l e le c tiv e h o s
d ia n s a n d
p it a l i z a t i o n s . A l l - c a u s e d e a t h w a s i n c l u d e d a s a s e c o n d
a s c o u n t s a n d p e r c e n t a g e s . B a la n c e b e t w e e n t r e a t m e n t
a ry o u tc o m e m e a s u re .
r a n g e s , a n d c a te g o r ic a l d a ta a re p r e s e n te d
g r o u p s w a s a s s e s s e d u s in g a b s o l u t e s t a n d a r d i z e d
d if
f e r e n c e s ( 2 4 ) . T h is m e a s u r e i n d e x e s t h e a b s o l u t e d i f f e r
D em o g ra p h ic C h aracteristics, C om orbidity,
a n d M ed ication s
W e a s s e s s e d s o c io e c o n o m ic s ta tu s b y a n n u a l n e t
e n c e in m e a n s o r p r o p o r t i o n s t o a p o o l e d
e s tim a te o f
th e
p o in ts
SD. A
v a lu e
le s s t h a n
10
p e rc e n ta g e
in d i
c a te s b a la n c e b e tw e e n g r o u p s .
f a m i l y i n c o m e , c a l c u l a t e d s e p a r a t e ly f o r p a t i e n t s a g e d
W e u s e d p r o p e n s ity s c o re m a tc h in g to e n s u re b a l
6 5 y e a rs o r y o u n g e r a n d th o s e o ld e r th a n 6 5 y e a rs t o
ance
a c c o u n t f o r c h a n g e s a fte r r e tir e m e n t, h ig h e s t a c h ie v e d
g r o u p s (2 5 ). T h e p r o p e n s ity s c o re w a s e s tim a te d b y f i t
e d u c a t i o n a l le v e l, a n d
t in g a n o n p a r s im o n io u s lo g is t ic r e g r e s s io n m o d e l w ith
c o h a b ita tio n
s ta t u s . A n n u a l n e t
in
b a s e li n e
f a m i l y i n c o m e w a s d i v i d e d i n t o t e r t i l e s o f lo w , m e d i u m ,
r e c e ip t o f a n
and
d e p e n d e n t v a r ia b le
h ig h
in c o m e .
le v e l w a s d i v i d e d
The
in to
h ig h e s t a c h ie v e d
3 g ro u p s :
e d u c a tio n a l
9 o r fe w e r y e a rs
of
a c te r is tic s
as
c h a r a c t e r is t ic s
a c ro s s
tre a tm e n t
e a r ly in v a s iv e t r e a t m e n t s t r a t e g y a s t h e
and
o b s e rv e d
p re tre a tm e n t c h a r
in d e p e n d e n t v a r ia b le s
( A p p e n d ix ) .
We
s c h o o l, h i g h s c h o o l o r v o c a t i o n a l t r a i n i n g , o r u n i v e r s i t y
m a t c h e d p a t i e n t s r e c e i v i n g a n e a r ly i n v a s iv e s t r a t e g y t o
d e g r e e . T h e s h o r t e s t d is t a n c e n e e d e d t o t r a v e l b y r o a d
th o s e
to
1:1
re a c h
a h o s p it a l w ith
PCI a n d
CABG
fa c ilitie s
w as
c a l c u l a t e d f o r e a c h p a t i e n t b y u s in g t h e r a n g e ( in k i l o
r e c e iv in g
a c o n s e r v a tiv e
r a tio a n d a p p lie d
a llo w
in v a s iv e a p p r o a c h
in a
a g r e e d y m a tc h in g a lg o r it h m
to
a m a x im a l d if f e r e n c e o f 0 .2 tim e s th e S D o f th e
m e te r s ) f r o m t h e p a t ie n t 's h o m e a d d r e s s as o f 1 J a n u
p r o p e n s i t y s c o r e . P a t ie n t s w i t h o u t a n a d e q u a t e
a ry
w e r e e x c l u d e d . T h is p r o c e d u r e w a s s t r a t i f i e d b y h o s p i
o f th e
year
o f a d m is s i o n .
D a ta
on
d e m o g r a p h ic
m a tc h
c h a r a c t e r is t ic s w e r e m is s i n g in 4 1 4 4 ( 7 % ) p a t i e n t s ; w e
ta l to
a d d re s s e d
in t r e a t m e n t , I C D - 1 0 c o d i n g , a n d a v a i l a b i l i t y o f c a r d ia c
th is
by
p e r f o r m in g
m u ltip le
im p u t a tio n
a n a ly s is ( A p p e n d i x , a v a i l a b le a t w w w . a n n a l s . o r g ).
w w w .a n n a ls .o r g
a c c o u n t f o r p o t e n t ia l a c r o s s - h o s p ita l d if fe r e n c e s
c a t h e t e r i z a t i o n f a c i li t i e s .
O riginal R esearch
A b s o lu t e t im e - t o - e v e n t m e a s u r e s w e r e c a lc u la te d
u s in g t h e
K a p la n - M e ie r e s t im a t o r f o r c a r d ia c a n d a ll
m e n t g r o u p in 3 9 h o s p it a ls ; t h e 7 e x c lu d e d h o s p it a ls
c o u ld n o t p r o v id e a n y m a t c h e d p a ir s ( A p p e n d ix F ig u r e
c a u s e d e a t h a n d t h e c u m u la t iv e in c id e n c e f u n c t io n f o r
1). S t a n d a r d iz e d d if f e r e n c e s d id
r e h o s p it a liz a t io n s , a c c o u n t in g f o r d e a t h as a c o m p e t in g
c e n ta g e
p o in t s
fo r
any
n o t exceed
o b s e rv e d
7 .7 p e r
p r e t r e a t m e n t v a r i
ris k . T h e c u m u la t iv e in c id e n c e c u r v e f o r c a r d ia c d e a th
a b le s , le n d in g s u p p o r t t o t h e a s s u m p t io n t h a t t h e v a r i
w a s g e n e ra te d
a b le s w e r e w e ll- b a la n c e d
in a c c o r d a n c e w it h t h e m e t h o d o f S i
b e tw e e n tr e a tm e n t g ro u p s
m o n a n d M a k u c h (2 6 ), a n d t h e c u r v e f o r r e h o s p it a liz a
( T a b le
t io n s w a s c r e a t e d b y a p p ly in g a n o n p a r a m e t r ic e x t e n
(5 6 .3 % ) p a t ie n t s h a d c a r d ia c c a t h e t e r iz a t io n
s io n o f t h e N e ls o n - A a le n e s t im a t o r . W e e s t im a t e d th e
d a y s 3 a n d 3 0 , 1 2 9 (1 .3 % ) h a d it b e t w e e n d a y s 31 a n d
1).
In t h e
c o n s e r v a tiv e
in v a s iv e
g ro u p ,
5549
b e tw e e n
r e la t iv e h a z a rd o f c a r d ia c a n d a ll- c a u s e d e a th b y u s in g
6 0 , a n d t h e r e m a in in g 4 1 7 9 (4 2 .4 % ) r e c e iv e d n o in v a
p r o p o r t io n a l h a z a rd s C o x r e g r e s s io n
m o d e ls t h a t in
s iv e e x a m in a t io n w it h in 6 0 d a y s . P a tie n t c h a r a c te r is t ic s
c lu d e d r e c e ip t o f a n e a r ly in v a s iv e s t r a t e g y as a t im e -
d if f e r e d a c ro s s t h e s e 3 g r o u p s , w it h t h e la s t 2 c o m p r is
d e p e n d e n t c o v a r ia te . T h is m o d e l im p lie d t h a t p a tie n ts
in g h ig h e r - r is k p a t ie n t s ( A p p e n d ix T a b le 3 , a v a ila b le a t
d id
w w w . a n n a ls . o r g ).
n o t c o n t r ib u t e
t im e
a t ris k t o
th e
e a r ly in v a s iv e
g r o u p u n til t h e d a y o f c a r d ia c c a th e t e r iz a t io n , t h u s lim
it in g
p o t e n t ia l
im m o r t a l t im e
T a b le 2 lis ts t r e a t m e n t c h a r a c te r is t ic s b y t r e a t m e n t
b ia s (2 7 ). B e c a u s e t h e
g r o u p in t h e p r o p e n s it y s c o r e - m a t c h e d c o h o r t . P a tie n ts
a s s u m p t io n o f c o n s t a n t h a z a rd d id n o t h o ld f o r r e h o s
r e c e iv in g a n e a r ly in v a s iv e s t r a t e g y w e r e m o r e lik e ly t o
p it a liz a tio n s , t im e - in d e p e n d e n t c o n d it io n a l lo g is t ic r e
h a v e s u b s e q u e n t PCI ( 6 9 .2 % vs. 3 6 .1 % ), h a d
g r e s s io n w a s p e r f o r m e d a n d o d d s r a tio s w it h 9 5 % C Is
h o s p it a l s ta y s ( m e d ia n , 4 vs. 5 d a y s ), a n d w e r e m o r e
s h o rte r
a re r e p o r t e d . W e t e s t e d t h e s e n s itiv ity o f o u r r e g r e s s io n
lik e ly
e s tim a te s t o
c h a r g e ( 7 3 .2 % vs. 5 8 .7 % ) th a n t h o s e in t h e c o n s e r v a tiv e
p o t e n t ia l v io la t io n s o f t h e a s s u m p t io n o f
to
in it ia t e
d u a l- a n t ip la t e le t
th e ra p y
a fte r
d is
ig n o r a b le t r e a t m e n t a s s ig n m e n t b y u s in g t h e m e t h o d s
in v a s iv e
d e s c r ib e d b y L in a n d c o lle a g u e s (2 8 ).
g r o u p w e r e e x a m in e d w it h c o r o n a r y a n g io g r a p h y a t an
In a n e x p lo r a t o r y a n a ly s is , w e t e s t e d f o r d if f e r e n c e s
in t h e
e s t im a t e d
tre a tm e n t
s u b g r o u p s . A a le n
a d d it iv e
e f f e c t w it h in
h a z a rd s
g ro u p .
M o re
p a t ie n t s
in
th e
e a r ly
in v a s iv e
in v a s iv e h e a r t c e n t e r ( 8 3 .9 % vs. 6 7 .7 % ).
p r e d e f in e d
In t h e p r o p e n s it y s c o r e - m a t c h e d c o h o r t , u s e o f a n
r e g r e s s io n s w e r e
e a r ly in v a s iv e t r e a t m e n t s t r a t e g y w a s a s s o c ia t e d w it h a
p e r f o r m e d t h a t in c lu d e d in t e r a c t io n t e r m s f o r t h e t r e a t
lo w e r ris k f o r a d v e r s e c a r d ia c e v e n ts t h a n a c o n s e r v a
m e n t in d ic a t o r a n d s u b g r o u p v a r ia b le s ( A p p e n d ix ) . A ll
s ig n if ic a n c e te s ts a n d C Is w e r e b a s e d o n r o b u s t SEs t o
d a y s , p a t ie n t s in t h e e a r ly in v a s iv e g r o u p h a d lo w e r c u
a c c o u n t f o r t h e m a t c h e d d e s ig n a n d r e f le c t e d v a r ia n c e
m u la t iv e in c id e n c e o f c a r d ia c d e a t h (5 .4 % vs. 6 .7 % ; d i f
w it h in
im p u t a t io n s . A ll h y p o th e s is te s ts
fe r e n c e , 1 .3 p e r c e n t a g e p o in t s ; a d ju s t e d h a z a rd r a tio
h a d a 2 - s id e d s ig n if ic a n c e le v e l o f 0 .0 5 . A n a ly s e s w e r e
[H R ], 0 .7 8 [9 5 % C l, 0 .6 9 t o 0 .8 8 ]; P < 0 .0 0 1 ) a n d r e h o s
and
b e tw e e n
p e r f o r m e d u s in g S ta ta , v e r s io n 1 3 .0 ( S ta ta C o r p ) .
p it a liz a t io n f o r M l ( 2 .8 % vs. 4 .1 % ; d if f e r e n c e , 1 .3 p e r
c e n t a g e p o in t s ; a d ju s t e d o d d s r a tio [O R ], 0 .6 8 [C l, 0 .5 8
R ole o f th e F u nd in g S ource
T h is s tu d y w a s s u p p o r t e d
to
b y th e
D e p a rtm e n t o f
C a r d io lo g y a t U n iv e r s ity H o s p ita l G e n t o f t e a n d g r a n ts
f r o m A b b o t t V a s c u la r R e s e a rc h a n d t h e M a s te r M a s o n
L a u r itz P e te r C h r is te n s e n a n d w if e K ir s te n S ig r id C h r is
t e n s e n F o u n d a t io n . T h e f u n d e r s h a d n o in v o lv e m e n t in
t h e d e s ig n o r c o n d u c t o f th e s tu d y ; c o lle c t io n , m a n a g e
m e n t, a n a ly s is , o r in t e r p r e t a t io n o f t h e d a ta ; o r p r e p a
r a tio n , r e v ie w , o r a p p r o v a l o f t h e m a n u s c r ip t.
0 .7 9 ];
P<
0 .0 0 1 ) t h a n
th o s e
in
th e
c o n s e r v a tiv e
g r o u p . T h e s e d if f e r e n c e s w e r e m a in t a in e d a t 6 0 d a y s
( c a r d ia c d e a t h : 5 .9 % vs. 7 .6 % ; d if f e r e n c e , 1 .7 p e r c e n t
age
p o in t s ; a d ju s t e d
HR, 0 .7 5 [C l, 0 .6 6 t o
0 .8 4 ]; P <
0 .0 0 1 ; r e h o s p it a liz a t io n f o r M l: 3 .4 % vs. 5 .0 % ; d if f e r
e n c e , 1 .6 p e r c e n t a g e p o in t s ; a d ju s t e d O R , 0 .6 7 [C l,
0 .5 8 t o 0 .7 7 ]; P < 0 .0 0 1 ) . S im ila r ly , p a t ie n t s h a v in g a n
e a r ly in v a s iv e s t r a t e g y a ls o h a d a lo w e r ris k f o r a ll- c a u s e
d e a th th a n t h o s e in t h e c o n s e r v a tiv e g r o u p a t 3 0 d a y s
(6 .5 % vs. 9 .1 % ; d if f e r e n c e , 2 .6 p e r c e n t a g e p o in t s ; a d
ju s t e d
e s u lt s
days
T h e o v e r a ll s t u d y c o h o r t in c lu d e d 5 4 6 9 4 p a tie n ts
HR, 0 .6 8 [C l, 0 .6 1
(7 .3 %
vs.
1 0 .6 % ;
t o 0 .7 6 ]; P <
d if f e r e n c e ,
0 .0 0 1 ) a n d 6 0
3 .3
p e rc e n ta g e
p o in t s ; a d ju s t e d HR, 0 .6 5 [C l, 0 .5 9 t o 0 .7 2 ]; P < 0 .0 0 1 )
a t 4 6 h o s p it a ls w ith a f ir s t A C S b e t w e e n 1 J a n u a r y 2 0 0 5
( T a b le
a n d 31 D e c e m b e r 2 0 1 1 ( T a b le 1 a n d A p p e n d ix F ig u r e
.a n n a ls .o r g ) .
1, a v a ila b le a t w w w . a n n a ls . o r g ). F o r t y - f o u r p e r c e n t h a d
s c o r e - m a t c h e d c o h o r t s u g g e s t e d t h a t t h e a s s o c ia t io n
an
e a r ly
f o llo w - u p
in v a s iv e
am ong
tre a tm e n t
s u r v iv in g
s tr a t e g y ,
and
m ean
p a t ie n t s w a s 6 0 d a y s . A l
b e tw e e n
and
an
A p p e n d ix
S u b g ro u p
F ig u r e
a n a ly s e s
2 , a v a ila b le
in
th e
in v a s iv e t r e a t m e n t s t r a t e g y
d e a th d if f e r e d
at w w w
p r o p e n s it y
and
c a r d ia c
b y s e x (P f o r in t e r a c t io n = 0 .0 2 1 ) , a g e
m o s t h a lf o f t h e h o s p it a ls h a d a n a n n u a l v o lu m e o f a t
(P < 0 .0 0 1 ) , d ia g n o s is (P < 0 .0 0 1 ) , a n d in d e x h o s p it a l
le a s t 4 0 0
(P = 0 .0 5 8 ) ( F ig u r e 2 ). D e s c r ip t iv e t a b le s s h o w e d t h a t
p a t ie n t s w ith A C S s , a n d
C A B G f a c ilit ie s ( A p p e n d ix T a b le
10%
h a d PC I a n d
1, a v a ila b le a t w w w
p a t ie n t c h a r a c te r is t ic s w e r e p o o r ly b a la n c e d w it h in t h e
.a n n a ls .o r g ) . A n in itia l c o m p a r is o n o f b a s e lin e c h a r a c
s tra ta
te r is t ic s b e t w e e n p a t ie n t s in t h e e a r ly a n d c o n s e r v a tiv e
u n r e lia b le .
in v a s iv e g r o u p s s h o w e d
and
h o s p it a l- r e la t e d
m a jo r im b a la n c e s in p a t ie n t -
fa c to rs
( A p p e n d ix
T a b le
2,
o f y e a r o f a d m is s io n ,
r e n d e r in g
th e s e
r e s u lts
W e c o n d u c t e d s e v e r a l s e n s itiv ity a n a ly s e s t o a s s e s s
t h e r o b u s tn e s s o f o u r r e s u lts . W e p e r f o r m e d a lt e r n a t e
s c o re -
p r o p e n s it y s c o r e m a t c h in g w it h s t r a t if ic a t io n f o r s u b
m a t c h e d c o h o r t in c lu d e d 9 8 5 2 p a t ie n t s in e a c h tr e a t -
g r o u p v a r ia b le s , t h u s e n s u r in g im p r o v e d b a la n c e in p a -
a v a ila b le
a t w w w . a n n a ls . o r g ). T h e
p r o p e n s it y
w w w .a n n a ls .o r g
O riginal R esearch
T a b le 1. Baseline Characteristics in the O verall Study C ohort and A m o n g Propensity Score-M atched Patients*
Characteristic
Demographic characteristics
Median age (range), y
Male
Net household income
Low
Medium
High
M issingf
Educational level
<9 y o f school
High school or vocational training
University degree
M issingf
No cohabitant partner
M issingf
Median distance to nearest invasive
heart center (range), km
M issingf
Risk factors
C oncomitant heart disease
Cardiac arrhythmia
Heart failure
Pulmonary edema
Cardiogenic shock
Valvular heart disease
Concom itant com orbidity
Cerebrovascular disease
Cancer
COPD
Diabetes with com plications
Acute renal failure
Chronic renal failure
PAOD
Pneumonia
Sepsis
Anemia
Respiratory insufficiency
Prior revascularization
Prior in-hospital bleeding
M edication before admission
Antihypertensive medication
Aspirin
Statin/other lipid-low ering drug
A ntidiabetic medication
Loop diuretic
Vitamin K antagonist
COPD medication
Index hospitalization
Hospital facilities
H igh-volum ef
PCI and CABG facilities
ACS diagnosis
Unstable angina pectoris
NSTEMI
STEMI
AMI w ithout specification
Year o f admission
2005
2006
2007
2008
2009
2010
2011
Conservative Invasive
Strategy (n = 9 8 5 2 )
68 (30-90)
34 793(63.6)
67 (30-90)
6388(64.8)
66 (30-90)
6428(65.3)
2.1
1.0
18 172 (33.2)
17 950(32.8)
18 316(33.5)
256(0.5)
3007 (30.5)
3182(32.3)
3620(36.7)
43(0.5)
2957(30.0)
3199(32.5)
3656(37.1)
40(0.4)
1.1
0.4
0.8
1.5
20 440(37.4)
22 634(41.4)
7782(14.2)
3838(7.0)
22 731 (41.6)
170(0.3)
43(0-198)
3718(37.7)
4202 (42.6)
1493(15.2)
439(4.5)
3931 (39.9)
31 (0.3)
42 (0-197)
3503(35.6)
4201 (42.6)
1478(15.0)
670(6.8)
3889(39.5)
29(0.3)
42 (0-197)
4.4
0.0
0.6
10.2
0.8
0.4
1.2
159(0.3)
32 (0.3)
29(0.3)
0.4
6357(11.6)
5204(9.5)
356(0.7)
357(0.7)
1849(3.4)
1001 (10.2)
819(8.3)
51 (0.5)
82(0.8)
255 (2.6)
976(9.9)
840(8.5)
57(0.6)
79(0.8)
275 (2.8)
1.0
0.7
1.4
0.3
1.2
2547 (4.7)
1495 (2.7)
3182(5.8)
2431 (4.4)
559(1.0)
938(1.7)
1365(2.5)
3676(6.7)
505 (0.9)
1537(2.8)
679(1.2)
1456(2.7)
1198(2.2)
356 (3.6)
204 (2.1)
461 (4.7)
344(3.5)
70(0.7)
120(1.2)
209(2.1)
444 (4.5)
48(0.5)
140(1.4)
85 (0.9)
308(3.1)
149(1.5)
373(3.8)
216(2.2)
440 (4.5)
362 (3.7)
87(0.9)
149(1.5)
226(2.3)
427 (4.3)
90(0.9)
146(1.5)
86(0.9)
318(3.2)
166(1.7)
1.1
0.7
1.0
1.1
2.2
2.6
1.4
1.0
4.8
0.8
0.1
0.6
1.6
27 747 (50.7)
17 525 (32.0)
15 115(27.6)
6760(12.4)
8546(15.6)
2786(5.1)
8055 (14.7)
5124 (52.0)
3262 (33.1)
3070 (31.2)
1164(11.8)
1231 (12.5)
441 (4.5)
1395(14.2)
5041 (51.2)
3161 (32.1)
3028(30.7)
1171 (11.9)
1140(12.1)
439(4.5)
1359(13.8)
1.6
2.1
1.1
0.3
1.2
0.1
1.2
37 800(69.1)
19 137 (35.0)
6819(69.2)
3095 (31.4)
6819(69.2)
3096(31.4)
0.0
0.0
8696(15.9)
17 976(32.9)
14 273 (26.1)
13 749 (25.1)
1987 (20.2)
3390(34.4)
1693(17.2)
2782 (28.2)
1885 (19.1)
3166(31.1)
1988(20.2)
2813(28.6)
2.8
4.9
7.7
0.9
8526(15.6)
8101 (14.8)
8064(14.7)
7751 (14.2)
7519(13.8)
7456(13.6)
7277(13.3)
1451 (14.7)
1349(13.7)
1283(13.0)
1383(14.1)
1454(14.8)
1413(14.3)
1519(15.4)
1411 (14.3)
1358(13.8)
1261 (12.8)
1402(14.2)
1461 (14.8)
1417 (14.4)
1542(15.7)
1.1
0.3
0.6
0.3
0.2
0.3
0.8
ASD
ACS = acute c o ronary syndrom e; A M I = acute m yocardial infa rction; ASD = a b solute standardized d iffe ren ce; CABG = coronary artery bypass g ra ft
surgery; COPD = ch ro n ic o b stru ctive p u lm ona ry disease; NSTEMI = non-S T-segm ent elevation m yocardial infa rction; PAOD = p e riphe ral arterial
occlusive disease; PCI = pe rcuta neo us coronary inte rventio n; STEMI = S T-segm ent eleva tion m yocardial infarction.
Values are num bers (p ercen tage s) unless oth erw ise indica ted,
t Values w ere im p u te d and w ere w ell-b alance d.
t > 40 0 cases o f ACS yearly.
D efine d using codes fro m th e International C lassification o f Diseases, 10th Revision: unstable angina pe ctoris (I200), NSTEMI (1210A, 1211 A, and
1214), STEMI (I210B, 1211 B, and 1213), and AMI w ith o u t spe cifica tion (1219).
w w w .a n n a ls .o rg
741
O riginal R esearch
C onservative Invasive
S trate g y (n = 9 8 5 2 )
5427(55.1)
4(0-60)
2542 (25.8)
5(0-60)
62.6
28.3
9852(100.0)
1(0-2)
5678(57.6)
5 (3-60)
121.3
128.2
1144(11.6)
5599(56.8)
1711 (17.4)
1398(14.2)
1122(19.8)
2741 (48.3)
928(16.3)
887(15.6)
22.7
17.1
2.9
3.9
1585 (16.1)
8267 (83.9)
1834 (32.3)
3844(67.7)
38.5
38.5
7656(77.7)
6813 (69.2)
1033(10.9)
1 (0-60)
4450 (42.2)
3557(36.1)
965 (9.8)
7(0-60)
77.7
70.3
2.3
96.3
377(4.9)
7279(95.1)
368(8.3)
4082 (91.7)
13.7
13.7
7207 (73.2)
8684(88.1)
7693(78.1)
5786(58.7)
8057(81.8)
6243(63.4)
31.0
17.7
32.7
ASD
H os p ita lizatio n
Invasive tre a tm e n t
Coronary angiography
Procedures
Median tim e to procedure (range),
Extent o f C A D t
Nonobstructive disease
1- o r 2-vessel disease
3-vessel disease
Missing
H ospitalf
Smaller hospital u n itt
Invasive heart center
Revascularization
Procedures
PCI
CABG
Median tim e to procedure (range),
H ospitalf
Smaller hospital u n itf
Invasive heart center
Dual-antiplatelet therapy
Aspirin
ADP receptor inhibitor
ADR = adenosine d ip h o s p h a te ; ASD = ab solute standardized diffe ren ce; CABG = co ronary artery bypass g ra ft surgery; CAD = corona
disease; PCI = pe rcutaneous coronary inte rventio n.
* Values are num bers (percentages) unless oth erw ise indica ted,
t Values are num bers (p ercen tage s o f procedures).
W ith cardiac catheterization facilities only.
Perform prim ary PCI and CABG in a d d itio n to cardiac catheterization.
Table 3. C um ulative Incide nee o f O utcom es in the Propensity Score-M atched and U nm atched C ohorts*
V a ria b le
C onservative Invasive
S trate g y (n = 9 8 5 2 )
P ropensity S core -M a tc h e d
C o h o rt (n = 1 9 7 0 4 )
U n m atched C ohort
(n = 5 4 6 9 4 )
3-d outcom es
Cardiac death
Rehospitalization fo r Ml
All-cause death
181 (2.9)
33 (0.3)
207 (3.3)
423 (3.2)
6(0.1)
519(4.0)
604(3.0)
39(0.2)
726(3.7)
1659 (3.0)
65 (0.1)
2086(3.8)
433 (5.4)
278(2.8)
527 (6.5)
761 (6.7)
402 (4.1)
1017 (9.1)
1194 (6.0)
680 (3.4)
1544(7.8)
3504 (6.4)
1891 (3.5)
4740 (8.7)
475 (5.9)
333 (3.4)
601 (7.3)
838(7.6)
491 (5.0)
1159(10.6)
1313(6.7)
824 (4.2)
1760(8.9)
3916(7.1)
2343 (4.3)
5535 (10.1)
3 0 -d outcom es
Cardiac death
Rehospitalization for Ml
All-cause death
6 0 -d outcom es
Cardiac death
Rehospitalization for Ml
All-cause death
Ml = m yocardial infarction.
* Values are num bers o f events (cum ulative incide nce p e r 100 patients at risk).
742
17 November 2015
www.annals.org
O riginal R esearch
F igure 1. C um ulative incidence curves fo r cardiac death and rehospitalization fo r Ml w ith in 60 d o f index hospitalization.
Rehospitalization for Ml
Cardiac Death
E
U
1~
10
---------- 1------------------1---------------- I
20
30
40
~r~
50
~r~
60
9050
9462
8907
9383
8834
9325
8775
9294
8692
9250
At risk, n
CIS 19 704
EIS 0
CIS
8906
9334
8601
9162
8443
9054
8344
8999
8274
8959
8224
8932
EIS
The HR and OR reflect outcomes at 60 d. CIS = conservative invasive strategy; EIS = early invasive strategy; HR = hazard ratio; Ml = myocardial
infarction; OR = odds ratio.
F igure 2. Associations betw een early versus conservative invasive strategies and cardiac death, by selected p a tie n t
characteristics.
Cardiac Deaths/Patients
(Cumulative Incidence per
100 Patients at Risk), n
Subgroup
Sex
Male
Female
Age
<75 y
Z75y
ACS diagnosis
Unstable angina
Myocardial infarction
Index hospital
PCI and CABG facilities
High-volume hospital
Other
Year of admission
2005-2007
2008-2009
2010-2011
EIS
CIS
Risk Difference
(95% Cl)
269/6388 (5.1)
206/3464 (7.3)
465/6428 (6.4)
373/3424 (9.8)
190/7049 (3.4)
285/2803 (11.9)
300/6909 (3.7)
538/2943 (17.3)
-0 .3 (-0.9 to 0.4)
-5 .4 (-7.3 to -3.5)
23/1987 (1.5)
452/7865 (6.9)
19/1885 (0.9)
819/7967 (9.3)
168/3095 (6.2)
144/3724 (5.0)
163/3033 (6.8)
334/3096 (9.9)
251/3723 (6.1)
253/3033 (7.2)
-3 .7 (-5.1 to -2.3)
-1.1 (-2.2 to 0.0)
-0 .4 (-1.8 to 1.0)
263/4083 (7.4)
137/2837 (6.2)
75/2932 (3.2)
395/4030 (8.9)
232/2863 (7.1)
211/2959 (6.4)
-1 .5 (-2.8 to -0.3)
-0 .9 (-2.3 to 0.5)
-3.2 (-4.3 to -2.1)
P Value for
Interaction
Hazard Ratio
(95%CI)
0.021
0.77 (0.64-0.93)
0.71 (0.57-0.88)
I - * I 1
<0.001
0.91 (0.73-1.13)
0.65 (0.53-0.79)
1 H
h*H ;
<0.001
1.51 (0.77-2.98)
0.72 (0.61-0.86)
---------I
'
i *
h *H
0.058
1 1
IH
0.61 (0.44-0.84)
0.76 (0.54-1.09)
0.91 (0.76-1.10)
i- h !
*di
W
j
0.81 (0.69-0.96)
0.83 (0.58-1.20)
0.47 (0.39-0.56)
0.93
i
0.125
Favor EIS
Favor CIS
Reported P values for additive interaction were adjusted for multiple comparisons by using the Holm-Bonferroni method. ACS = acute coronary
syndrome; CABG = coronary artery bypass grafting; CIS = conservative invasive strategy; EIS = early invasive strategy; PCI = percutaneous coronary
intervention.
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O riginal R esearch
timates, suggesting th a t our results are applicable to
patients with NSTE-ACSs.
is c u s s io n
Note: Dr. Hansen had full access to all o f the data in th e study
and takes responsibility fo r the in te g rity o f the data and the
accuracy o f th e data analysis.
S t u d y p r o t o c o l a n d d a ta
(e -m a il, k im .w a d t.h a n s e n @ re g io n h .d k ).
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A d L ibitum
erran t gull
the sun is once again behind me and I
sight
wake my senses
opened
D.A. Frater, MD
Dallas, Texas
C urrent A u th o r Address: D.A. Frater, MD; e-mail, dfrater@ ebarrow m edical.m d.
www.annals.org