Drug-eluting stents in acute myocardial infarction: updated meta-analysis of randomized trials
13
REVIEW Drug-eluting stents in acute myocardial infarction: updated meta-analysis of randomized trials Alban Dibra • Klaus Tiroch • Stefanie Schulz • Henning Kelbæk • Christian Spaulding • Gerrit J. Laarman • Marco Valgimigli • Emilio Di Lorenzo • Christoph Kaiser • Ilkka Tierala • Julinda Mehilli • Gianluca Campo • Leif Thuesen • Maarten A. Vink • Martin J. Schalij • Roberto Violini • Albert Scho ¨mig • Adnan Kastrati Received: 23 August 2009 / Accepted: 15 February 2010 / Published online: 11 March 2010 Ó Springer-Verlag 2010 Abstract Background Use of drug-eluting stents in patients with acute myocardial infarction (AMI) remains an ‘‘off label’’ indication due to concerns regarding their performance in this patient subset. Methods We searched Medline, the Cochrane Central Register of Controlled Trials, and Internet-based sources of information on clinical trials in cardiology for randomized trials comparing drug-eluting stents with bare-metal stents in patients with AMI. Hazard ratios for the composite of death or recurrent myocardial infarction, (primary safety endpoint), reintervention (primary efficacy endpoint), death, recurrent myocardial infarction, and stent thrombo- sis were calculated performing a meta-analysis of 14 ran- domized trials with 7,781 patients. Results There was no difference in the hazard of death or recurrent myocardial infarction (hazard ratio, 0.91; [95% CI 0.75–1.09]) between patients treated with drug-eluting stents versus patients treated with bare-metal stents. Treatment with drug-eluting stents resulted in a significant reduction in the hazard of reintervention (0.41 [95% CI 0.32–0.52]). The hazards of death (0.90 [95% CI 0.71– 1.15]), myocardial infarction (0.81 [95% CI 0.63–1.04]), and stent thrombosis (0.84 [95% CI 0.61–1.17]) were not significantly different between patients treated with drug- eluting stents versus patients treated with bare-metal stents. Conclusions Use of drug-eluting stents in patients with AMI is safe and markedly reduces the need for reinter- vention as compared to bare-metal stents. A. Dibra Á K. Tiroch Á S. Schulz Á J. Mehilli Á A. Scho ¨mig Á A. Kastrati (&) Deutsches Herzzentrum, Technische Universita ¨t, Lazarettstr. 36, 80636 Munich, Germany e-mail: [email protected] H. Kelbæk Rigshospitalet, University of Copenhagen, Copenhagen, Denmark C. Spaulding Assistance Publique-Ho ˆpitaux de Paris (AP-HP), Cochin Hospital, Paris 5 Medical School Rene Descartes University and INSERM U780-Avenir, Paris, France G. J. Laarman King’s College Hospital, London, UK M. Valgimigli Á G. Campo University of Ferrara, Ferrara, Italy E. Di Lorenzo A.O.R.N. ‘‘S. G. Moscati’’, Avellino, Italy C. Kaiser University of Basel, Basel, Switzerland I. Tierala Helsinki University Central Hospital, Helsinki, Finland L. Thuesen Skejby Sygehus, Skejby, Denmark M. A. Vink Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands M. J. Schalij Leiden University Medical Center, Leiden, The Netherlands R. Violini San Camillo Hospital, Rome, Italy 123 Clin Res Cardiol (2010) 99:345–357 DOI 10.1007/s00392-010-0133-y
Transcript of Drug-eluting stents in acute myocardial infarction: updated meta-analysis of randomized trials
REVIEW
Drug-eluting stents in acute myocardial infarction:updated meta-analysis of randomized trials
Alban Dibra • Klaus Tiroch • Stefanie Schulz • Henning Kelbæk • Christian Spaulding • Gerrit J. Laarman •
Marco Valgimigli • Emilio Di Lorenzo • Christoph Kaiser • Ilkka Tierala • Julinda Mehilli • Gianluca Campo •
Leif Thuesen • Maarten A. Vink • Martin J. Schalij • Roberto Violini • Albert Schomig • Adnan Kastrati
Received: 23 August 2009 / Accepted: 15 February 2010 / Published online: 11 March 2010
� Springer-Verlag 2010
Abstract
Background Use of drug-eluting stents in patients with
acute myocardial infarction (AMI) remains an ‘‘off label’’
indication due to concerns regarding their performance in
this patient subset.
Methods We searched Medline, the Cochrane Central
Register of Controlled Trials, and Internet-based sources of
information on clinical trials in cardiology for randomized
trials comparing drug-eluting stents with bare-metal stents
in patients with AMI. Hazard ratios for the composite of
death or recurrent myocardial infarction, (primary safety
endpoint), reintervention (primary efficacy endpoint),
death, recurrent myocardial infarction, and stent thrombo-
sis were calculated performing a meta-analysis of 14 ran-
domized trials with 7,781 patients.
Results There was no difference in the hazard of death or
recurrent myocardial infarction (hazard ratio, 0.91; [95%
CI 0.75–1.09]) between patients treated with drug-eluting
stents versus patients treated with bare-metal stents.
Treatment with drug-eluting stents resulted in a significant
reduction in the hazard of reintervention (0.41 [95% CI
0.32–0.52]). The hazards of death (0.90 [95% CI 0.71–
1.15]), myocardial infarction (0.81 [95% CI 0.63–1.04]),
and stent thrombosis (0.84 [95% CI 0.61–1.17]) were not
significantly different between patients treated with drug-
eluting stents versus patients treated with bare-metal
stents.
Conclusions Use of drug-eluting stents in patients with
AMI is safe and markedly reduces the need for reinter-
vention as compared to bare-metal stents.
A. Dibra � K. Tiroch � S. Schulz � J. Mehilli � A. Schomig �A. Kastrati (&)
Deutsches Herzzentrum, Technische Universitat,
Lazarettstr. 36, 80636 Munich, Germany
e-mail: [email protected]
H. Kelbæk
Rigshospitalet, University of Copenhagen,
Copenhagen, Denmark
C. Spaulding
Assistance Publique-Hopitaux de Paris (AP-HP),
Cochin Hospital, Paris 5 Medical School Rene Descartes
University and INSERM U780-Avenir, Paris, France
G. J. Laarman
King’s College Hospital, London, UK
M. Valgimigli � G. Campo
University of Ferrara, Ferrara, Italy
E. Di Lorenzo
A.O.R.N. ‘‘S. G. Moscati’’, Avellino, Italy
C. Kaiser
University of Basel, Basel, Switzerland
I. Tierala
Helsinki University Central Hospital, Helsinki, Finland
L. Thuesen
Skejby Sygehus, Skejby, Denmark
M. A. Vink
Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
M. J. Schalij
Leiden University Medical Center, Leiden, The Netherlands
R. Violini
San Camillo Hospital, Rome, Italy
123
Clin Res Cardiol (2010) 99:345–357
DOI 10.1007/s00392-010-0133-y
Keywords Myocardial infarction � Angioplasty �Drug-eluting stents � Restenosis � Thrombosis
Introduction
Although coronary angioplasty with routine implantation
of bare-metal stents has been established as the reper-
fusion strategy of choice for patients with acute
myocardial infarction [2, 8, 13, 22, 23, 32, 34, 51], the
long-term success of this strategy has been hampered by
the frequent development of restenosis [28, 44, 46, 51].
Drug-eluting stents have been shown to reduce the
restenosis risk and need for repeat revascularization
procedures associated with use of bare-metal stents in
various lesion and patient subsets [12, 20]. However,
there has been limited evidence on the role of drug-
eluting stents in patients with acute myocardial infarc-
tion. The benefits and safety issues related to the use of
these devices have been evaluated in several randomized
and non-randomized studies. While the superior clinical
efficacy of drug-eluting stents has not been consistently
shown in these studies [10, 25, 30, 40, 42, 49, 50], there
have been reports that use of drug-eluting stents during
primary percutaneous coronary intervention could be
associated with an increased risk of stent thrombosis [6,
16, 35]. After performing a meta-analysis of randomized
trials of patients with acute myocardial infarction we
found that drug-eluting stent reduce reintervention rate
without increasing the risk of adverse outcomes as
compared to bare-metal stents [19]. However, the num-
ber of patients studied was not large enough to allow a
reliable estimation of rare adverse events. In a recent
statement, the Food and Drug Administration considered
that ‘‘off label’’ use of drug-eluting stents, such as their
use in patients with acute myocardial infarction, was
associated with an increased risk of adverse outcome
compared with ‘‘on label’’ use and asked for additional
data to determine optimal treatments for complex
patients [47].
Since we performed our meta-analysis of 8 randomized
trials including 2,786 patients [19], several other random-
ized trials comparing drug-eluting stents with bare-metal
stents in acute myocardial infarction, including Harmo-
nizing Outcomes with Revascularization and Stents in
Acute Myocardial Infarction (HORIZONS-AMI) study,
have been completed [4, 11, 18, 21, 45, 48]. Important new
data obtained from the evaluation of 5,000 additional
patients enrolled in these trials have now become available.
Furthermore, the new trials have provided more informa-
tion on the paclitaxel-eluting stent which, compared to the
sirolimus-eluting stent, has been less frequently studied in
the early trials of drug-eluting stents in patients with acute
myocardial infarction. Therefore, we incorporated the new
evidence into an updated meta-analysis to consolidate and
extend current knowledge on the safety and efficacy of
drug-eluting stents after primary percutaneous coronary
intervention.
Methods
Search and selection process
We searched the MEDLINE database, the Cochrane
Central Register of Controlled Trials, and Internet-based
sources of information on the results of clinical trials
in cardiology (http://www.cardiosource.com/clinicaltrials,
http://www.theheart.org, http://www.clinicaltrialresults.com,
http://www.clinicaltrials.gov, http://www.europcr.com, and
http://www.tctmd.com) through January 2010. We used
these key words: ‘‘acute myocardial infarction’’, ‘‘primary
angioplasty’’, ‘‘stenting’’, ‘‘bare-metal stent’’, ‘‘drug-elut-
ing stent’’, ‘‘sirolimus-eluting stent’’, ‘‘paclitaxel-eluting
stent’’, ‘‘randomized trial’’. We also identified previous
meta-analyses and relevant reviews and editorials from
major medical journals published within the last year and
assessed these sources for possible information on trials of
interest.
Eligible for this meta-analysis was randomized studies
comparing drug-eluting stents with bare-metal stents in
patients with acute myocardial infarction undergoing pri-
mary percutaneous coronary intervention, if information on
outcomes of interest were reported or made available by
the trial investigators for a mean follow-up period of at
least 6 months. No restriction criteria were imposed with
regard to the form of study publication.
Data extraction and quality assessment
Studies were searched and reviewed independently by two
of the authors (A.D. and K.T.); those meeting the inclusion
criteria were selected for further analysis. A total of 15
trials were identified [4, 10, 11, 18, 21, 25, 30, 36, 40, 42,
45, 48–50]. The trial of Pasceri et al. [36] was excluded
because it reported only preliminary data of the first 34
patients over a follow-up of 4 months. Finally, 14 trials,
shown in Table 1, were included in this meta-analysis [4,
10, 11, 14, 18, 21, 25, 30, 36, 40, 42, 45, 48–50].
Individual patient data were obtained from primary
investigators for 9 trials with 3,846 patients (Table 1).
Summary data were obtained from publication source for 4
trials. In the remaining trial, we used risk estimates
reported in the presentation of the results of this trial [45].
346 Clin Res Cardiol (2010) 99:345–357
123
Ta
ble
1M
ain
char
acte
rist
ics
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ls
Stu
dy
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Dea
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LE
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Clin Res Cardiol (2010) 99:345–357 347
123
Ta
ble
2E
nd
po
int
defi
nit
ion
sin
each
tria
l
Stu
dy
Rec
urr
ent
my
oca
rdia
lin
farc
tio
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ein
terv
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on
Ste
nt
thro
mb
osi
s
BA
SK
ET
-AM
I
[40
]
Ty
pic
alch
est
pai
nw
ith
eith
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pic
alri
se(a
nd
fall
)o
f
card
iac
enzy
mes
or
new
pat
ho
log
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-wav
es/S
T-T
wav
ech
ang
eso
nE
CG
Inte
rven
tio
n(P
CI
or
CA
BG
)d
riv
enb
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lesi
on
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e
sam
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dia
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init
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An
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gra
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the
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isch
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clin
ical
even
t
DE
DIC
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[21
]
Acu
teco
ron
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me
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Kle
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C2
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esth
e
up
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no
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nco
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no
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K-
MB
con
cen
trat
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An
yC
AB
Go
rP
CI
of
the
targ
etle
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nd
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pto
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ns
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emia
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ere
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s
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Defi
nit
est
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sac
cord
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emic
Res
earc
hC
on
sort
ium
clas
sifi
cati
on
[5]
Di
Lo
ren
zo[1
0]
Rec
urr
ence
of
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sym
pto
ms
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hty
pic
alE
CG
chan
ges
and
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ease
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-MB
or
tro
po
nin
An
yC
AB
Go
rP
CI
of
the
targ
etv
esse
lin
the
pre
sen
ceo
f
sym
pto
ms
or
sig
ns
of
isch
emia
An
gio
gra
ph
ical
lyd
ocu
men
ted
thro
mb
us
wit
hin
the
sten
t
asso
ciat
edto
typ
ical
ches
tp
ain
and
ST
-seg
men
t
mo
difi
cati
on
inth
ete
rrit
ory
of
the
infa
rct
rela
ted
ves
sel
wit
ho
rw
ith
ou
ta
sig
nifi
can
tri
seo
fen
zym
es
Dia
zd
ela
Lle
raa
[11]
Rec
urr
ent
ches
tp
ain
wit
hS
T-T
chan
ges
acco
mp
anie
db
y
incr
ease
inC
Ko
rC
K-M
Ble
vel
s[
1.5
tim
esth
e
pre
vio
us
val
ue
ifB
48
h,
or
thei
rel
evat
ion
abo
ve
the
up
per
no
rmal
lev
elif
[4
8h
fro
mth
ein
itia
lin
farc
tio
n
An
yC
AB
Go
rP
CI
du
eto
sten
osi
sC
50
%w
ith
inth
e
sten
tso
r5
-mm
dis
tal
or
pro
xim
alse
gm
ents
adja
cen
tto
the
sten
t
Acu
teco
ron
ary
syn
dro
me
wit
hd
ocu
men
tati
on
of
eith
er
ves
sel
occ
lusi
on
or
thro
mb
us
wit
hin
or
adja
cen
tto
a
pre
vio
usl
ysu
cces
sfu
lly
sten
ted
ves
sel
or
my
oca
rdia
l
infa
rcti
on
inth
ed
istr
ibu
tio
no
fth
etr
eate
dv
esse
lo
r
dea
thn
ot
clea
rly
attr
ibu
tab
leto
oth
erca
use
s
HA
AM
U-
ST
EN
T[1
4]
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nic
alp
ictu
reo
fm
yo
card
ial
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rcti
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T-
seg
men
tch
ang
esan
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evat
edca
rdia
cm
ark
ers
or
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iog
rap
hic
sten
tth
rom
bo
sis
An
yC
AB
Go
fth
eta
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ves
sel
or
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CI
du
eto
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iog
rap
hic
rest
eno
sis
inth
ep
rese
nce
of
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pto
ms
or
sig
ns
of
isch
emia
Acu
teS
T-s
egm
ent
elev
atio
nm
yo
card
ial
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rcti
on
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s
ang
iog
rap
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thro
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us
HO
RIZ
ON
S-
AM
I[4
5]
Ifth
eb
asel
ine
CK
/CK
-MB
lev
els
are
no
rmal
:A
new
elev
atio
no
ftr
op
on
ino
rC
K-M
B[
39
UL
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r
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[3
9U
LN
)w
ith
in2
4h
po
st-P
CI.
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eb
asel
ine
CK
-MB
(or
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)le
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sar
eel
evat
ed,b
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do
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ente
dto
be
fall
ing
:re
curr
ent
ches
tp
ain
or
isch
emic
equ
ival
ent
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pto
ms
last
ing
C3
0m
in,
and
anab
solu
teri
seo
f
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-MB
[3
9U
LN
(or
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teri
sein
CK
[2
9U
LN
)ab
ov
eth
ep
rev
iou
sn
adir
lev
elw
ith
in
24
hp
ost
-PC
I.(3
)If
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pea
kC
K-M
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rC
K)
has
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t
yet
bee
nre
ach
edb
efo
reP
CI:
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urr
ent
ches
tp
ain
or
isch
emic
equ
ival
ent
sym
pto
ms
last
ing
C3
0m
in,
or
new
elec
tro
card
iog
rap
hic
chan
ges
con
sist
ent
wit
ha
rein
farc
tio
nan
dth
en
ext
CK
-MB
(or
CK
)le
vel
mea
sure
dap
pro
xim
atel
y8
to1
2h
afte
rth
eev
ent
is
elev
ated
by
atle
ast
50
%ab
ov
eth
ep
rev
iou
sle
vel
or
[3
9U
LN
,w
hic
hev
eris
gre
ater
.
(C)
MI
dia
gn
osi
saf
ter
coro
nar
yar
tery
by
pas
ssu
rger
y:
any
CK
-MB
(or
CK
)C
10
9U
LN
wit
hin
24
ho
f
op
erat
ion
and
incr
ease
dat
leas
t5
0%
ov
erth
em
ost
rece
nt
pre
op
erat
ion
lev
els,
or
any
CK
-MB
(or
CK
)
C5
9U
LN
wit
hin
24
ho
fo
per
atio
nan
din
crea
sed
at
leas
t5
0%
ov
erth
em
ost
rece
nt
pre
op
erat
ion
lev
els
and
new
sig
nifi
can
t(C
0.0
4s)
Qw
aves
inC
2co
nti
gu
ou
s
elec
tro
card
iog
rap
hic
lead
s
An
yis
chem
ia-d
riv
enre
pea
tP
CI
of
the
targ
etle
sio
n
(in
clu
din
g5
-mm
pro
xim
alan
d/o
rd
ista
lm
arg
ins)
or
CA
BG
of
the
targ
etv
esse
l
Defi
nit
est
ent
thro
mb
osi
sac
cord
ing
toth
eA
cad
emic
Res
earc
hC
on
sort
ium
clas
sifi
cati
on
[5]
348 Clin Res Cardiol (2010) 99:345–357
123
Ta
ble
2co
nti
nu
ed
Stu
dy
Rec
urr
ent
my
oca
rdia
lin
farc
tio
nR
ein
terv
enti
on
Ste
nt
thro
mb
osi
s
MIS
SIO
Na
[50]
Dev
elo
pm
ent
of
new
Q-w
aves
on
EC
Go
ra
tro
po
nin
-T
rise
abo
ve
no
rmal
([2
5%
abo
ve
pre
vio
us
val
ue)
wit
h
sym
pto
ms
or
nee
dfo
rre
inte
rven
tio
n
An
yC
AB
Go
rP
CI
of
the
targ
etv
esse
lA
ng
iog
rap
hic
ally
do
cum
ente
dth
rom
bu
sw
ith
inth
est
ent
and
/or
typ
ical
ches
tp
ain
wit
hre
curr
ent
ST
-seg
men
t
elev
atio
nin
the
terr
ito
ryo
fth
ein
farc
tre
late
dv
esse
lin
com
bin
atio
nw
ith
asi
gn
ifica
nt
rise
of
tro
po
nin
lev
els
and
/or
the
pre
sen
ceo
fn
ewQ
-wav
esin
the
terr
ito
ryo
f
the
infa
rct
rela
ted
ves
sel
MU
LT
I-
ST
RA
TE
GY
[48
]
Rec
urr
ent
isch
emic
sym
pto
ms
wit
hE
CG
chan
ges
or
an
incr
ease
inC
Ktw
ice
the
up
per
no
rmal
lim
ito
rfu
rth
er
elev
atio
n[
50
%th
anth
ep
rev
iou
slo
wes
tv
alu
ean
d
afte
r7
day
sa
typ
ical
incr
ease
and
dec
reas
eo
fn
ecro
sis
bio
mar
ker
lev
els
or
furt
her
elev
atio
n[
50
%th
anth
e
pre
vio
us
low
est
val
ue
An
yC
AB
Go
ra
seco
nd
PC
Io
fth
eta
rget
ves
sel
dri
ven
by
clin
ical
sym
pto
ms
of
my
oca
rdia
lis
chem
iaw
ith
a
po
siti
ve
stre
sste
sto
ris
chem
icE
CG
chan
ges
atre
st
attr
ibu
tab
leto
the
targ
etv
esse
lin
the
pre
sen
ceo
f
[7
0%
lum
inal
sten
osi
s
Defi
nit
est
ent
thro
mb
osi
sac
cord
ing
toth
eA
cad
emic
Res
earc
hC
on
sort
ium
clas
sifi
cati
on
[5]
PA
SS
ION
[25
]E
ith
erp
ath
olo
gic
alQ
wav
eso
nE
CG
or
anin
crea
sein
the
crea
tin
ek
inas
ele
vel
C2
tim
esth
eu
pp
ern
orm
al
lev
elo
r5
0%
hig
her
than
the
pre
vio
us
val
ue
(if
they
wer
est
ill
elev
ated
)w
ith
sym
pto
ms
or
nee
dfo
r
rein
terv
enti
on
An
yC
AB
Ga
PC
Io
fth
eta
rget
ves
sel
or
du
eto
ang
iog
rap
hic
rest
eno
sis
inth
ep
rese
nce
of
sym
pto
ms
or
sig
ns
of
isch
emia
An
gio
gra
ph
icd
ocu
men
tati
on
of
eith
erv
esse
lo
cclu
sio
n
or
thro
mb
us
form
atio
nw
ith
in,
or
adja
cen
tto
,th
e
sten
ted
seg
men
t
SE
LE
CT
ION
[4]
Rec
urr
ent
isch
emic
sym
pto
ms
or
EC
Gch
ang
es
acco
mp
anie
db
yin
crea
sein
CK
or
CK
-MB
lev
els
[1
.5ti
mes
the
pre
vio
us
val
ue
ifB
48
h,
or
elev
atio
n
[3
tim
esth
eu
pp
ern
orm
alle
vel
ifn
ewsy
mp
tom
s
app
eare
d[
48
hfr
om
the
init
ial
infa
rcti
on
An
yC
AB
Go
rP
CI
of
the
targ
etle
sio
nin
the
pre
sen
ceo
f
dia
met
erst
eno
sis
C5
0%
wit
hin
the
tota
lan
aly
sis
seg
men
t
An
gio
gra
ph
icp
roo
fo
fv
esse
lo
cclu
sio
n,
any
my
oca
rdia
l
infa
rcti
on
inth
ete
rrit
ory
of
the
sten
ted
ves
sel,
any
dea
thfr
om
card
iac
cau
ses
(acu
tean
dsu
bac
ute
thro
mb
osi
s),
or
recu
rren
tm
yo
card
ial
infa
rcti
on
wit
h
ang
iog
rap
hic
pro
of
of
occ
lusi
on
of
the
sten
ted
ves
sel
(lat
eth
rom
bo
sis)
SE
SA
MI
[30]
Rec
urr
ent
isch
emic
sym
pto
ms
or
EC
Gch
ang
es
acco
mp
anie
db
yan
incr
ease
inca
rdia
cen
zym
es
C2
tim
esth
eu
pp
ern
orm
alle
vel
(if
val
ues
wer
e
pre
vio
usl
yn
orm
aliz
ed)
or
50
%h
igh
erth
anth
e
pre
vio
us
val
ue
(if
they
wer
est
ill
elev
ated
)
An
yC
AB
Go
fth
eta
rget
ves
sel
or
aP
CI
du
eto
ang
iog
rap
hic
rest
eno
sis
inth
ep
rese
nce
of
sym
pto
ms
or
sig
ns
of
isch
emia
An
gio
gra
ph
icev
iden
cein
the
pre
sen
ceo
fan
acu
te
coro
nar
ysy
nd
rom
e
ST
RA
TE
GY
[49
]
Rec
urr
ent
isch
emic
sym
pto
ms
or
EC
Gch
ang
es
acco
mp
anie
db
yan
incr
ease
inca
rdia
cen
zym
esab
ov
e
the
no
rmal
lim
it(i
fv
alu
esw
ere
pre
vio
usl
yn
orm
aliz
ed)
or
50
%h
igh
erth
anth
ep
rev
iou
sv
alu
e(i
fth
eyw
ere
stil
lel
evat
ed)
An
yC
AB
Go
rP
CI
of
the
targ
etv
esse
lin
the
pre
sen
ceo
f
sym
pto
ms
or
sig
ns
of
isch
emia
An
gio
gra
ph
icev
iden
cein
the
pre
sen
ceo
fcl
inic
al
sym
pto
ms
or
EC
Gch
ang
essu
gg
esti
ve
of
acu
te
isch
emia
TIT
AX
AM
I
[18
]
Rec
urr
ent
isch
emic
sym
pto
ms
acco
mp
anie
db
yan
incr
ease
of
tro
po
nin
Io
rT
abo
ve
the
up
per
lim
ito
f
no
rmal
or
new
rise
[5
0%
abo
ve
the
pre
vio
usl
y
mea
sure
dtr
op
on
inI
or
Tle
vel
Rep
eat
PC
Io
fth
eta
rget
lesi
on
totr
eat
ast
eno
sis[
50
%
wit
hin
the
sten
to
rin
the
seg
men
ts5
mm
pro
xim
alo
r
dis
tal
toth
est
ent
dri
ven
by
sym
pto
ms/
sig
ns
of
isch
emia
or
CA
BG
of
the
targ
etv
esse
ld
ue
toin
-ste
nt
rest
eno
sis
or
oth
erco
mp
lica
tio
ns
of
the
targ
etle
sio
n
Defi
nit
est
ent
thro
mb
osi
sac
cord
ing
toth
eA
cad
emic
Res
earc
hC
on
sort
ium
clas
sifi
cati
on
[5]
Clin Res Cardiol (2010) 99:345–357 349
123
The outcomes of interest were the composite of all-
cause death or recurrent myocardial infarction (primary
safety endpoint), reintervention (primary efficacy end-
point), all-cause death, recurrent myocardial infarction,
and stent thrombosis. The definitions of outcomes of
interest used in individual studies are shown in Table 2. To
assure consistency in the definition of stent thrombosis
across different trials we used only figures of definite stent
thrombosis from those trials, where stent thrombosis was
defined according to the classification of Academic
Research Consortium [5].
Each trial was evaluated for the adequacy of allocation
concealment, performance of the analysis according to the
intention-to-treat principle, and blind assessment of the
outcomes of interest. We used the criteria recommended by
Altman et al. [1] and Juni et al. [17] to assess the adequacy
of allocation concealment. In 3 trials, a modified intention-
to-treat principle, i.e. exclusion of patients who did not
receive the study stent, was used [11, 42, 50].
Data synthesis and analysis
Hazard ratios (HRs) with 95% confidence intervals (CIs)
were computed as summary statistics. The pooled HRs
were calculated using the DerSimonian and Laird method
for random effects [9]. The individual study HRs were
calculated using the Mantel–Cox test for 9 trials with
individual patient data (Table 1). For the HORIZONS-
AMI trial we used the hazard ratios as recently reported
[45]. For the remaining 4 trials, risk estimates were cal-
culated based on the summary data obtained from publi-
cation source (Table 1).
We used the Cochran-test to assess heterogeneity across
trials. We also calculated the I2 statistic to measure the
consistency between trials with values of 25, 50, and 75%
showing respectively, low, moderate, and high heteroge-
neity [15].
We performed sensitivity analyses by comparing the
treatment effects obtained with each trial removed con-
secutively from the analysis with the overall treatment
effects. Meta-regression analysis was used to explore the
influence of the recommended duration of clopidogrel
treatment and length of follow-up on the main safety
endpoint as well as the influence of the recommended
duration of clopidogrel treatment on stent thrombosis.
We assessed publication bias with respect to the primary
endpoint of safety—the composite of death and recurrent
myocardial infarction was evaluated using a funnel
plot as well as the adjusted rank correlation test [3].
Results were considered statistically significant at two-
sided P \ 0.05. Statistical analysis was performed by
using the Stata software, version 9.2 (Stata Corp, Col-
lege Station, Tex).Ta
ble
2co
nti
nu
ed
Stu
dy
Rec
urr
ent
my
oca
rdia
lin
farc
tio
nR
ein
terv
enti
on
Ste
nt
thro
mb
osi
s
TY
PH
OO
Na
[42
]
Rec
urr
ence
of
clin
ical
sym
pto
ms
or
the
occ
urr
ence
of
elec
tro
card
iog
rap
hic
chan
ges
acco
mp
anie
db
ya
new
elev
atio
no
fca
rdia
cen
zym
es(1
.5ti
mes
the
pre
vio
us
val
ue
or
3ti
mes
the
up
per
lim
ito
fn
orm
al
An
yC
AB
Go
fth
eta
rget
ves
sel
or
aP
CI
du
eto
ang
iog
rap
hic
rest
eno
sis
inth
ep
rese
nce
of
sym
pto
ms
or
sig
ns
of
isch
emia
,o
ro
nly
du
eto
sev
ere
rest
eno
sis
(C7
0%
dia
met
erst
eno
sis)
Acu
tean
dsu
bac
ute
sten
tth
rom
bo
sis
wer
ed
efin
edas
ang
iog
rap
hic
pro
of
of
ves
sel
occ
lusi
on
,an
yre
curr
ent
Q-w
ave
my
oca
rdia
lin
farc
tio
nin
the
terr
ito
ryo
fth
e
sten
ted
ves
sel,
or
any
dea
thfr
om
card
iac
cau
ses.
Lat
e
sten
tth
rom
bo
sis
was
defi
ned
asan
yre
curr
ent
my
oca
rdia
lin
farc
tio
nw
ith
ang
iog
rap
hic
pro
of
of
ves
sel
occ
lusi
on
b
BA
SK
ET
-AM
IB
asel
Ste
nt
Ko
sten
Eff
ekti
vit
ats
inA
cute
My
oca
rdia
lIn
farc
tio
ntr
ial;
DE
DIC
AT
ION
the
Dru
gE
luti
on
and
Dis
tal
Pro
tect
ion
inA
cute
My
oca
rdia
lIn
farc
tio
nT
rial
;H
AA
MU
-
ST
EN
TT
he
Hel
sin
ki
area
acu
tem
yo
card
ial
infa
rcti
on
-tre
atm
ent
re-e
val
uat
ion
—S
ho
uld
the
pat
ien
tg
eta
dru
g-e
luti
ng
or
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orm
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l;H
OR
IZO
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ith
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nts
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Pro
spec
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ized
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ntr
oll
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rial
toE
val
uat
eth
eE
ffica
cyo
fD
rug
-Elu
tin
gS
ten
tsv
ersu
sB
are-
Met
alS
ten
ts
for
the
Tre
atm
ent
of
Acu
teM
yo
card
ial
Infa
rcti
on
;M
UL
TI-
ST
RA
TE
GY
the
Mu
ltic
entr
eE
val
uat
ion
of
Sin
gle
Hig
h-D
ose
Bo
lus
Tir
ofi
ban
ver
sus
Ab
cix
imab
Wit
hS
iro
lim
us-
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tin
gS
ten
to
r
Bar
e-M
etal
Ste
nt
inA
cute
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oca
rdia
lIn
farc
tio
nS
tud
y;
PA
SS
ION
the
Pac
lita
xel
-Elu
tin
gS
ten
tv
ersu
sC
on
ven
tio
nal
Ste
nt
inM
yo
card
ial
Infa
rcti
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wit
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T-S
egm
ent
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vat
ion
tria
l;
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LE
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ION
Sin
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ter
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350 Clin Res Cardiol (2010) 99:345–357
123
Results
Included in this meta-analysis were 14 trials with 7,781
patients (Fig. 1). Table 1 shows the main characteristics of
these trials. Patient populations of individual trials varied
from 80 patients to 3,006 patients. The mean age of study
participants of individual studies varied from 59 to
64 years. The sirolimus-eluting stent was the single drug-
eluting stent evaluated in 6 trials [11, 30, 42, 48–50], the
paclitaxel-eluting stent was the single drug-eluting stent
evaluated in 5 trials [4, 14, 18, 25, 45], both sirolimus and
paclitaxel-eluting stents were evaluated in 3 trials [10, 21,
40]. In one of the trials either the sirolimus-eluting stent,
the paclitaxel-eluting stent, or the zotarolimus-eluting stent
was compared to the bare-metal control [21]. The
recommended duration of thienopyridine therapy after the
procedure was 3 [48, 49], 6 [10, 18, 25, 40, 42], 9 [4, 11],
and 12 months [14, 21, 30, 50]. Average length of follow-
up varied from 7 to 24 months. A clinical endpoint was the
primary endpoint in 8 studies [10, 11, 18, 25, 40, 42, 48].
Angiographic restenosis, late loss or stent volume
obstruction by intravascular ultrasound were the primary
endpoints in 5 trials [4, 14, 21, 30, 50]. One study used a
composite of clinical and angiographic outcomes as the
primary endpoint [49].
Figure 2 shows the hazard ratio of the primary safety
endpoint—the composite of all-cause death or recurrent
myocardial infarction—associated with drug-eluting stents
versus bare-metal stents. There was no significant differ-
ence in the hazard of this endpoint between the two treat-
ment modalities using the random effects model: pooled
HR, 0.91 (95% CI 0.75–1.09; P = 0.28). The fixed effects
model yielded identical results: pooled HR, 0.91 (95% CI
0.75–1.09; P = 0.28). There was no significant heteroge-
neity (P = 0.55) and no inconsistency across trials
(I2 = 0%). Sequential exclusion of each individual trial
from the analysis of overall mortality yielded HRs that
ranged from 0.87 (95% CI 0.72–1.04) to 0.94 (95% CI
0.77–1.13) and were not significantly different from the
overall HR (P C 0.74). Meta-regression analysis showed
that neither the length of follow-up (P = 0.98) nor
the recommended duration of clopidogrel treatment
(P = 0.70) had any influence on the overall result.
Figure 3 shows the hazard ratio of the primary efficacy
endpoint—reintervention—associated with drug-eluting
stents versus bare-metal stents. There was a large reduction
in the hazard of reintervention with drug-eluting stents
compared to bare-metal stents using the random effects
model: (pooled HR, 0.41 [95% CI 0.32–0.52; P \ 0.001]).
Selection Criteria
Randomized trials of DES vs. BMS in patients withacute myocardial infarction
15 randomized trials identified (n=7815)
1 trial excludeddue to incompletereporting of results
14 trials included in the final analysis (n=7781)
DES (n=4727) BMS (n=3054)
Fig. 1 Flowchart of included studies. DES drug-eluting stent, BMSbare-metal stent
DES Group BMS Group Hazard Ratio(95% CI)
0.95 (0.40-2.24)
1.36 (0.67-2.76)
0.53 (0.25-1.12)
1.21 (0.26-5.69)
1.35 (0.57-3.24)
0.97 (0.70-1.32)
0.56 (0.25-1.22)
0.78 (0.44-1.38)
0.82 (0.44-1.50)
0.65 (0.10-4.11)
0.50 (0.17-1.46)
0.76 (0.38-1.52)
2.12 (0.93-4.84)
0.85 (0.38-1.89)
0.91 (0.75-1.09)
Test for Heterogeneity P=0.55Test for Inconsistency I 2 = 0.0%Test for Overall Effect z = 1.07 (P=0.28)
Source
BASKET-AMI
DEDICATION
Di Lorenzo
Diaz de la Llera
HAAMU-STENT
HORIZONS-AMI
MISSION
MULTI-STRATEGY
PASSION
SELECTION
SESAMI
STRATEGY
TITAX AMI
TYPHOON
OVERALL
142 74
313 313
180 90
60 54
82 82
2257 749
158 152
372 372
310 309
40 40
160 160
87 88
211 214
355 357
4727 3054
No. of Patients
1.1 10
Hazard Ratio (95% CI)for death or recurrent myocardial infarction
Favors DES Favors BMS
Fig. 2 Hazard ratios of all-
cause death or recurrent
myocardial infarction associated
with drug-eluting stent versus
bare-metal stent. DES drug-
eluting stent, BMS bare-metal
stent, CI confidence interval.
The size of the data marker is
proportional to the weight of the
individual studies
Clin Res Cardiol (2010) 99:345–357 351
123
The fixed effects model yielded similar results: pooled HR,
0.44 (95% CI 0.36–0.52; P \ 0.001). There was no sig-
nificant heterogeneity (P = 0.14) and low-to-moderate
inconsistency across trials (I2 = 29.9%). Sequential
exclusion of each individual trial from the analysis of death
yielded HRs that ranged from 0.38 (95% CI 0.30–0.48) to
0.43 (95% CI 0.34–0.55) and were not significantly dif-
ferent from the overall HR (P C 0.67). Meta-regression
analysis showed that neither the type of drug-eluting stent
(P = 0.27) nor the length of follow-up (P = 0.51) had any
influence on the overall result. We evaluated separately the
outcome of reintervention for trials with angiographic
follow-up (pooled HR, 0.36 [95% CI 0.27–0.48]) and
without angiographic follow-up (pooled HR, 0.54 [95% CI
0.36–0.8]) and we found no significant difference in the
results (P for interaction = 0.12).
Figure 4 shows the hazard ratio of all-cause death
associated with drug-eluting stents versus bare-metal
stents. There was no significant difference in the hazard of
all-cause death between the two treatment modalities using
the random effects model: (pooled HR, 0.90 [95% CI 0.71–
1.15; P = 0.41]). The fixed effects model identical similar
results: HR, 0.90 ([95% CI 0.71–1.15; P = 0.41).There
was no significant heterogeneity (P = 0.51) and no
inconsistency across trials (I2 = 0%).
Figure 5 shows the hazard ratio of recurrent myocardial
infarction associated with drug-eluting stents versus bare-
metal stents. The hazard of myocardial infarction was
No. of Patients
DES Group BMS Group Hazard Ratio(95%CI)
0.55 (0.22-1.35)
0.37 (0.21-0.67)
0.23 (0.09-0.58)
0.12 (0.01-2.41)
0.48 (0.16-1.39)
0.59 (0.43-0.83)
0.26 (0.09-0.72)
0.31 (0.16-0.60)
0.68 (0.36-1.28)
0.11 (0.02-0.53)
0.34 (0.14-0.80)
0.34 (0.15-0.78)
0.74 (0.37-1.49)
0.28 (0.16-0.48)
0.41 (0.32-0.52)
Test for Heterogeneity P=0.14Test for Inconsistency I2 = 29.9%Test for Overall Effect z = 7.30 (P<0.001)
Source
BASKET-AMI
DEDICATION
Di Lorenzo
Diaz de la Llera
HAAMU-STENT
HORIZONS-AMI
MISSION
MULTI-STRATEGY
PASSION
SELECTION
SESAMI
STRATEGY
TITAX AMI
TYPHOON
OVERALL
142 74
313 313
180 90
60 54
82 82
2257 749
158 152
372 372
310 309
40 40
160 160
87 88
211 214
355 357
4727 3054
1.1 10
Hazard Ratio (95% CI)for target lesion revascularization
Favors DES Favors BMS
Fig. 3 Hazard ratios of
reintervention associated with
drug-eluting stent versus bare-
metal stent. DES drug-eluting
stent, BMS bare-metal stent, CIconfidence interval. The size of
the data marker is proportional
to the weight of the individual
studies
DES Group BMS Group Hazard Ratio(95% CI)
0.51 (0.16-1.59)
1.86 (0.79-4.38)
0.58 (0.19-1.73)
1.37 (0.22-8.52)
2.57 (0.80-8.31)
0.99 (0.64-1.55)
0.47 (0.09-2.63)
0.73 (0.33-1.60)
0.69 (0.35-1.37)
0.32 (0.03-3.18)
0.29 (0.06-1.38)
0.83 (0.36-1.93)
1.22 (0.37-4.07)
1.01 (0.38-2.68)
0.90 (0.71-1.15)
Test for Heterogenity P=0.51Test for Inconsistency I2 = 0.0%Test for Overall Effect z = 0.83 (P=0.41)
Source
BASKET-AMI
DEDICATION
Di Lorenzo
Diaz de la Llera
HAAMU-STENT
HORIZONS-AMI
MISSION
MULTI-STRATEGY
PASSION
SELECTION
SESAMI
STRATEGY
TITAX AMI
TYPHOON
OVERALL
142 74
313 313
180 90
60 54
82 82
2257 749
158 152
372 372
310 309
40 40
160 160
87 88
211 214
355 357
4727 3054
No. of Patients
1.1 10
Hazard Ratio (95% CI)for death
Favors DES Favors BMS
Fig. 4 Hazard ratios of all-
cause death associated with
drug-eluting stent versus bare-
metal stent. DES drug-eluting
stent, BMS bare-metal stent, CIconfidence interval. The size of
the data marker is proportional
to the weight of the individual
studies
352 Clin Res Cardiol (2010) 99:345–357
123
lower among patients treated with drug-eluting stents ver-
sus bare-metal stents using the random effects model,
although the difference did not achieve statistical signifi-
cance (pooled HR, 0.81 (95% CI 0.63–1.04; P = 0.10]).
The fixed effects model yielded identical results: HR, 0.81
(95% CI 0.63–1.04; P = 0.10). There was no significant
heterogeneity (P = 0.73) and no inconsistency across trials
(I2 = 0%).
Figure 6 shows the hazard ratio of stent thrombosis
associated with drug-eluting stents versus bare-metal
stents. The hazard of stent thrombosis was comparable
between patients treated with drug-eluting stents compared
to patients treated with bare-metal stents using the random
effects model: (pooled HR, 0.84 [95% CI 0.61–1.17;
P = 0.30]). The fixed effects model yielded identical
results: pooled HR, 0.84 (95% CI 0.61–1.17; P = 0.30).
DES Group BMS Group Hazard Ratio(95%CI)
1.13 (0.35-3.69)
0.31 (0.07-1.37)
0.49 (0.17-1.40)
0.90 (0.06-14.72)
0.35 (0.06-2.06)
0.81 (0.54-1.21)
0.60 (0.25-1.42)
0.70 (0.33-1.49)
0.82 (0.25-2.69)
3.08 (0.12-77.80)
0.99 (0.20-4.95)
0.85 (0.31-2.35)
2.00 (0.87-4.58)
0.80 (0.22-2.99)
0.81 (0.63-1.04)
Test for Heterogenity P=0.73Test for Inconsistency I2 = 0.0%Test for Overall Effect z = 1.64 (P=0.10)
Source
BASKET-AMI
DEDICATION
Di Lorenzo
Diaz de la Llera
HAAMU-STENT
HORIZONS-AMI
MISSION
MULTI-STRATEGY
PASSION
SELECTION
SESAMI
STRATEGY
TITAX AMI
TYPHOON
OVERALL
142 74
313 313
180 90
60 54
82 82
2257 749
158 152
372 372
310 309
40 40
160 160
87 88
211 214
355 357
4727 3054
No. of Patients
1.1 10
Hazard Ratio (95% CI)for recurrent myocardial infarction
Favors DES Favors BMS
Fig. 5 Hazard ratios of
recurrent myocardial infarction
associated with drug-eluting
stent versus bare-metal stent.
DES drug-eluting stent, BMSbare-metal stent, CI confidence
interval. The size of the data
marker is proportional to the
weight of the individual studies
DES Group BMS Group Hazard Ratio(95%CI)
1.53 (0.16-14.81)
0.27 (0.06-1.23)
0.50 (0.03-8.04)
1.83 (0.16-20.74)
0.33 (0.06-1.78)
0.86 (0.53-1.41)
0.96 (0.06-15.52)
0.81 (0.34-1.93)
1.00 (0.20-4.91)
0.33 (0.01-8.22)
2.01 (0.18-22.37)
0.20 (0.01-4.15)
7.31 (0.89-59.93)
0.92 (0.42-2.02)
0.84 (0.61-1.17)
Test for Heterogenity P=0.70Test for Inconsistency I2 = 0.0%Test for Overall Effect z = 1.03 (P=0.30)
Source
BASKET-AMI
DEDICATION
Di Lorenzo
Diaz de la Llera
HAAMU-STENT
HORIZONS-AMI
MISSION
MULTI-STRATEGY
PASSION
SELECTION
SESAMI
STRATEGY
TITAX AMI
TYPHOON
OVERALL
142 74
313 313
180 90
60 54
82 82
2257 749
158 152
372 372
310 309
40 40
160 160
87 88
211 214
355 357
4727 3054
No. of Patients
1.1 10
Hazard Ratio (95% CI)for stent thrombosis
Favors DES Favors BMS
Fig. 6 Hazard ratios of stent
thrombosis associated with
drug-eluting stent versus bare-
metal stent. DES drug-eluting
stent, BMS bare-metal stent, CIconfidence interval. The size of
the data marker is proportional
to the weight of the individual
studies
Standard error log (hazard ratio)
Lo
g (
haz
ard
rat
io)
0 .5 1
-2
-1
0
1
2
Fig. 7 Funnel plot (with pseudo 95% confidence intervals) to detect
possible publication bias
Clin Res Cardiol (2010) 99:345–357 353
123
We found no significant heterogeneity (P = 0.70) and no
inconsistency across trials (I2 = 0%). Meta-regression
analysis showed that the recommended duration of clopi-
dogrel treatment (P = 0.80) had no influence on stent
thrombosis.
We found no evidence of publication bias with respect
to the composite of death or recurrent myocardial infarc-
tion using the Begg funnel plot (Fig. 7) and rank correla-
tion test (P = 0.75).
Finally, we compared sirolimus-eluting stents with
paclitaxel-eluting stents regarding the different outcomes
evaluated in this meta-analysis. The pooled hazard ratio for
the outcome of death or recurrent myocardial infarction
was 0.71 (95% CI 0.54–0.93) for trials evaluating siroli-
mus-eluting stents and 1.02 (95% CI 0.81–1.28) for trials
evaluating paclitaxel-eluting stents; we found a significant
difference in the results (P for interaction = 0.05). The
pooled hazard ratio for the outcome of reintervention was
0.30 (95% CI 0.22–0.41) for trials evaluating sirolimus-
eluting stents and 0.56 (95% CI 0.45–0.70) for trials
evaluating paclitaxel-eluting stents; the difference in the
results (P for interaction = 0.001). In addition, we analyzed
separately the outcomes of death, recurrent myocardial, and
stent thrombosis for trials evaluating sirolimus-eluting
stents and trials evaluating paclitaxel-eluting stents and we
found no significant difference in the results (P for inter-
action = 0.41, 0.23, and 0.68, respectively).
Discussion
This updated meta-analysis has several strengths. First,
inclusion of HORIZONS-AMI and several other trials that
were recently completed more than doubled the number of
patients who were evaluated in the prior meta-analyses [7,
19, 37]. Availability of a large amount of data regarding the
outcome of 7,781 patients (4,727 treated with drug-eluting
stents) enrolled in 14 randomized trials enabled us to perform
a more reliable meta-analytic evaluation of rare adverse
events and benefits related with the use of drug-eluting stents
as compared with bare-metal stents in acute myocardial
infarction. Second, the new trials included a large number of
patients treated with paclitaxel-eluting stents. Earlier studies
mainly focused on the sirolimus-eluting stent and evidence
on the outcome of patients treated with the paclitaxel-eluting
stent was limited. Inclusion of more than 2,500 additional
patients treated with paclitaxel-eluting stents in this meta-
analysis allows drawing reliable conclusions regarding the
performance of both sirolimus-eluting and paclitaxel-eluting
stents in patients undergoing percutaneous coronary inter-
vention for acute myocardial infarction.
Coronary implantation of drug-eluting stents in patients
with acute myocardial infarction remains an ‘‘off label’’
indication [47]. Although some of the studies in this field
have questioned the clinical efficacy of drug-eluting stents
versus bare-metal stents [25], the main concern related to
their use in patients with acute myocardial infarction has
been an increased risk of adverse outcomes [39]. Several
studies have reported that, compared to bare-metal stents,
sirolimus-eluting and paclitaxel-eluting stents provoke
delayed healing, impaired endothelialization, vascular
dysfunction, hypersensitivity reaction, and persistent fibrin
deposition which produce the conditions that have been
related to the development of stent thrombosis [27].
Recently, findings from an autopsy study suggested an
increased risk of thrombotic complications in patients
treated with drug-eluting stents for acute myocardial
infarction and this was explained with the delayed vessel
healing at the culprit site in patients with acute myocardial
infarction as compared to patients with stable angina [31].
There have been several observational studies that have
linked drug-eluting stent implantation in acute myocardial
infarction with an increased risk of stent thrombosis. Park
et al. [35] found that primary stenting with implantation of
sirolimus-eluting or paclitaxel-eluting stents in patients
with acute myocardial infarction was a major predictor for
acute and subacute stent thrombosis. Sianos et al. [41]
reported that a larger thrombus burden was associated with
a higher risk of stent thrombosis. However, registry studies
of patients with acute ST-segment elevation myocardial
infarction have not shown an increased risk of stent
thrombosis or thrombosis-related events with drug-eluting
stents as compared with bare-metal stents [26, 33, 38].
Our meta-analysis shows that implantation of drug-
eluting stents in patients with acute myocardial infarction is
as safe as implantation of bare-metal stents. The pooled
hazard ratios for the composite of all-cause death or
recurrent myocardial infarction, all-cause death, recurrent
myocardial infarction, and stent thrombosis showed a
similar hazard for these adverse outcomes among patients
treated with drug-eluting and bare-metal stents. Meta-
regression analysis did not identify any influence of the
type of drug-eluting stent used, either sirolimus-eluting or
paclitaxel-eluting stent, on the outcome of mortality. Thus,
the use of both drug-eluting stents is safe. It has been
suggested that drug-eluting stents increase the risk of late
adverse outcome [39]. Mean length of follow-up in the
studies included in our meta-analysis varied from 7 to
24 months. Meta-regression analysis that was used to
explore the influence of duration of follow-up on all-cause
death did not identify any impact of follow-up duration on
the primary safety outcome. On the other hand, the 3-year
data reported from Kukreja et al. [24] showed not only a
similar risk of adverse events among patients with acute
myocardial infarction treated with drug-eluting stents as
compared to patients treated with bare-metal stents, but
354 Clin Res Cardiol (2010) 99:345–357
123
even a trend toward a better outcome with one of the drug-
eluting stents. Furthermore, the 2-year data from Massa-
chusetts registry showed a decreased risk of mortality with
drug-eluting stents [29]. However, the results from these
registry studies should be interpreted with caution.
We found that use of drug-eluting stents was associated
with a 59% reduction in the hazard of reintervention. This
figure clearly shows the significant superiority of drug-
eluting stents over bare-metal stents in patients with acute
myocardial infarction. The overall result was not influ-
enced by the length of follow-up. Similarly, the type of
drug-eluting stent used had no influence on the outcome of
reintervention, which shows the efficacy of both drug-
eluting stents, the sirolimus-eluting, and paclitaxel-eluting
stent. The finding of this meta-analysis regarding the
superior efficacy of drug-eluting stents as compared to
bare-metal stents in patients with acute myocardial
infarction is in the same line with other studies and meta-
analyses that have shown the efficacy of drug-eluting stents
in other settings of complex patients and lesions [12, 43].
In some of the studies included in this meta-analysis
drug-eluting stents were not shown superior to bare-metal
stents. This was observed more frequently in those studies
which enrolled smaller number of patients or used the
paclitaxel-eluting stent as a comparator. Although it has
been suggested that routine angiographic follow-up might
increase reintervention rates thereby influencing study
outcomes, we did not find any difference in this outcome
between studies with or without angiographic follow-up.
This meta-analysis has several limitations. Its results
cannot be extended to drug-eluting stents other than the
sirolimus-eluting and paclitaxel-eluting stents. The maxi-
mum length of follow-up reported in studies included in
our meta-analysis was 24 months. Considering the concern
related to the potential for increased risk of late thrombotic
events in patients treated with drug-eluting stents, it is
necessary to perform studies with longer follow-up to
provide more reassurance on the safety of using drug-
eluting stents in patients with acute myocardial infarction.
Furthermore, despite the increased statistical power of this
meta-analysis, the failure to detect a clinically relevant
difference between drug-eluting stents and bare-metal
stents regarding the occurrence of rare adverse events is
still possible. About half of the patients evaluated in this
meta-analysis were contributed by the HORIZONS-AMI
trial. No patient-level data were available for this trial and
this should be considered as a limitation of this meta-
analysis, despite the fact that the removal of this trial from
the general analysis did not influence the overall result.
Finally, patients with some high-risk characteristics, such
as those with cardiogenic shock, have been excluded from
the trials that were evaluated in this meta-analysis.
Therefore, our conclusion cannot be extrapolated to the
whole population of patients with acute myocardial
infarction.
In conclusion, the results of this meta-analysis show that
during medium-term follow-up the use of drug-eluting
stents in patients with acute myocardial infarction is safe
and results in a marked reduction in the need of
reintervention.
Acknowledgments Dr. Spaulding report having received lecture
fees from Abbott, Boston Scientific, Cordis and Lilly. Dr. Laarman
reports having served on the advisory board of Boston Scientific and
received lecture fees from Cordis and Medtronic. Dr. Valgimigli
reports having received honoraria for lectures, consultancy and
research grants from Merck. Dr. Tierala reports having received
unrestricted research grants via the Helsinki University Hospital
Research Institute from Boston Scientific, Lilly, Roche and Sanofi-
Aventis as well as lecture fees from Bristol-Myers-Squibb, Glaxo-
Smith-Kline, MSD, Lilly, Sanofi-Aventis. Dr. Schalij reports having
received unrestricted research grants from Biotronik, Boston Scien-
tific and Medtronic. Dr. Kastrati reports having received lecture fees
from Bristol-Myers, Biotronik, Cordis, Lilly, the Medicines, Med-
tronic, and Sanofi-Aventis. Drs. Dibra, Tiroch, and Kastrati had full
access to and take full responsibility for the integrity of the data. All
authors have read and agree to the manuscript as written.
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