International Journal of Cardiology 133 (2009) 213 – 222

www.elsevier.com/locate/ijcard

Efficacy and safety of drug-eluting stents in ST-segment elevation

myocardial infarction: A meta-analysis of randomized trials
Giuseppe De Luca a,⁎, Gregg W. Stone b , Harry Suryapranata c , Gerrit Jan Laarman d ,
Maurizio Menichelli e , Christoph Kaiser f , Marco Valgimigli g , Emilio Di Lorenzo h ,
Maurits T. Dirksen d , Christian Spaulding i , Undine Pittl f , Roberto Violini e ,
Gianfranco Percoco g , Paolo Marino a
a
Division of Cardiology, Ospedale “Maggiore della Carità”, Eastern Piedmont University, Novara, Italy
b
The Cardiovascular Research Foundation, Lenox Hill Heart and Vascular Institute New York City, USA
c
Isala Klinieken, Hospital De Weezenlanden, Zwolle, The Netherlands
d
Department of Interventional Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
e
Division of Cardiology, San Camillo Hospital, Rome, Italy
f
Division of Cardiology, University Hospital Basel, Switzerland
g
Institute of Cardiology, University of Ferrara, Ferrara, Italy
h
Division of Cardiology, “S.G. Moscati”, Avellino, Italy
i
Assistance Publique-Hopitaux de Paris Cochin Hospital, Paris 5 Medical School Rene Descartes University and INSERM Unite 780 Avenir, Paris, France
Received 22 August 2007; received in revised form 11 December 2007; accepted 14 December 2007
Available online 3 April 2008

Abstract

Background: Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more
pronounced among STEMI patients. Thus, the aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of
DES as compared to BMS in patients undergoing primary angioplasty for STEMI.
Methods: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed
randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction,
reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on
study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were
extracted by two investigators. Disagreements were resolved by consensus.
Results: A total of 11 trials were included in the meta-analysis, involving 3605 patients (1888 or 52.3% randomized to DES and 1719 or
47.7% randomized to BMS).
At 12 months follow-up, no significant difference was observed in mortality (4.1% vs 4.4%, OR [95% CI] = 0.91 [0.66–1.27], p = 0.59,
reinfarction (3.1% vs 3.4%, OR [95% CI] = 0.85 [0.58, 1.23], p = 0.38 or stent thrombosis (1.6% vs 2.2%, OR [95% CI] = 0.76 [0.47, 1.23],
p = 0.22), whereas DES were associated with a significant reduction in TVR (5.0% vs 12.6%, OR [95% CI] = 0.36 [0.28, 0.47], p b 0.0001).
Safety and efficacy of DES were confirmed at 18 to 24 months follow-up (data available from 4 trials including 1178 patients).
Conclusions: This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES and PES, as compared to
BMS, are safe and associated with a significant reduction in TVR at 1 and 2 years follow-up.
© 2008 Published by Elsevier Ireland Ltd.

Keywords: Primary angioplast; STEMI; DES; Meta-analysis; Randomized trials

⁎ Corresponding author. Ospedale “Maggiore della Carità”, Eastern Piedmont University, C.so Mazzini, 18, 24100 Novara, Italy. Tel.: +39 0321 3733141; fax:
+39 0321 3733407.
E-mail address: g.deluca@diagram-zwolle.nl (G. De Luca).

0167-5273/$ - see front matter © 2008 Published by Elsevier Ireland Ltd.

doi:10.1016/j.ijcard.2007.12.040
214 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222

Table 1
Characteristics of randomized trials included in the meta-analysis
Study Period Study Stent type Gp IIb– Primary Definition of stent FU Routine Dual oral
design IIIa endpoint thrombosis by protocol (months) angiographic antiplatelet
(number inhibitors follow-up therapy
of patients) (%)
STRATEGY [20] 2003– DES SES and Bx 100 Combined Angiographic evidence in the 24 81% Aspirin
2004 (n = 87) Velocity death, reMI, presence of clinical symptoms or indefinitely;
vs BMS stroke and ECG changes suggestive of Clopidogrel
(n = 88) restenosis at acute ischemia for at least
8 months 3 months
PASSION [21] 2003– DES PES vs 73.8 Combined Angiographic documentation of 18 0 Aspirin i
2004 (n = 310) Express-2 or death, reMI, either vessel occlusion or ndefinitely;
vs BMS Libertè or TLR at thrombus formation within or Clopidogrel
(n = 309) 1 year adjacent to, the stented segment. for at least
6 months
TYPHOON [22] 2003– DES SES or 71.5 Target-vessel Acute or subacute stent 12 24% Aspirin
2004 (n = 355) BMS a failure at thrombosis were defined as indefinitely;
vs BMS 1 year angiographic proof of vessel Clopidogrel
(n = 357) occlusion, any recurrent Q-wave for at least
myocardial infarction in the 6 months
territory of the stented vessel, or
any death from cardiac causes.
Late stent thrombosis was defined
as any recurrent myocardial
infarction with angiographic
proof of vessel occlusion.
SESAMI [22] 2003– DES SES or 74.9 Angiographic Angiographic evidence of in the 12 52% Aspirin
2004 (n = 160) BMS a restenosis at presence of acute coronary indefinitely;
vs BMS 1-year syndrome Clopidogrel
(n = 160) follow-up for at least
12 months
Di Lorenzo et al. 2003– DES SES, PES, 100 Combined Angiographically documented 24 0 Aspirin
[23] 2004 (n = 180) BMS a death, ReMI, thrombus within the stent indefinitely;
vs BMS TVR and associated with ST-segment Clopidogrel
(n = 90) stroke at modification in the territory of the for at least
6 months infarct-related vessel with or 12 months
without a significant rise in
cardiac enzymes
BASKET-AMI. [25] 2003– SES SES, PES, 65 Combined Angiographic evidence in the 18 0 Aspirin
2004. (n = 76) Vision death, ReMI, presence of an ischemic clinical indefinitely;
or PES TVR and event Clopidogrel
(n = 67) stroke at for at least
vs BMS 6 months 6 months
(n = 74)
HAAMU-STENT 2004– PES PES, BMS 70 Late loss at Acute ST-segment elevation 12 88% Aspirin
[28] 2005. (n = 82) vs 9-month myocardial infarction plus indefinitely;
BMS angiographic angiographic thrombus. Clopidogrel
(n = 82) follow-up for 12
months
MISSION [29] 2004– DES SES, BMS 80 Late loss at Angiographically documented 12 82% Aspirin
2006 (n = 158) 9-month thrombus within the stent and/or indefinitely;
vs BMS angiographic typical chest pain with recurrent Clopidogrel
(n = 152) follow-up ST-segment elevation in the for 12
territory of the infarct-related months
vessel in combination with a
significant rise of troponin levels
and/or the presence of new
Q-waves in the territory of the
infarct-related vessel
DEDICATION [32] 2005– DES DES: 96 Late loss (at Angiographic documentation of 8 100% Aspirin
2006 (n = 313) Cypher, 8 month target-vessel occlusion or both indefinitely;
vs BMS Taxus, follow-up). reduced Thrombolysis in Clopidogrel
(n = 313) Endeavor; Myocardial Infarction flow and the for 12
BMS: presence of thrombus in the stented months
Vision, region coupled with at least one of
 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222 215

Table 1 (continued )
Study Period Study Stent type Gp IIb– Primary Definition of stent FU Routine Dual oral
design IIIa endpoint thrombosis by protocol (months) angiographic antiplatelet
(number inhibitors follow-up therapy
of patients) (%)
Driver, the following: a) new acute onset of
Express, ischemic symptoms at rest; b) new
Libertè ischemic electrocardiogram changes
suggestive of acute ischemia; or
c) typical rise and fall in cardiac
biomarkers; or 2) evidence of recent
thrombus within the stent determined
at autopsy or via examination of
tissue retrieved after thrombectomy
SELECTION [30] 2004– DES TAXUS vs 100 Stent volume Angiographic documentation of 8 100% Aspirin
2005 (n = 40) Express) obstruction target-vessel occlusion or both indefinitely;
vs BMS by IVUS at reduced Thrombolysis in Myocardial Clopidogrel
(n = 40) 7 month Infarction flow and the presence of for 9
follow-up thrombus in the stented region months
coupled with at least one of the
following: a) new acute onset of
ischemic symptoms at rest; b) new
ischemic electrocardiogram changes
suggestive of acute ischemia; or
c) typical rise and fall in cardiac
biomarkers; or 2) evidence of recent
thrombus within the stent determined
at autopsy or via examination of
tissue retrieved after thrombectomy
Diaz De la Llera 2004– DES Cypher vs 100 Death, non Acute coronary syndrome with 12 100% Aspirin
et al. [31] 2006 (n = 60) BMS) fatal MI and angiographic documentation of indefinitely;
vs BMS recurrernt either vessel occlusion or Clopidogrel
(n = 54) myocardial thrombus within or adjacent to a for 9
ischemia previously successfully stented months
at 1-year vessel or, in the absence of
follow-up angiographic confirmation, either MI
in the distribution of the treated
vessel or death not clearly attributable
to other causes.
SES = sirolimus-eluting stent; PES = paclitaxel-eluting stent; BMS = bare-metal stent; ReMI = reinfarction; TVR = target-vessel revascularization; TLR = target-
lesion revascularization.
a
The choice of the stent was left to the discretion of the operator.

The treatment of ST-segment elevation myocardial
infarction (STEMI) has substantially evolved over the past
decades, mainly due to the adoption of pharmacological and/
or mechanical reperfusion therapies [1,2], and improvements
in antiplatelet and anti-coagulation therapies [3,4]. Coronary
stenting has been shown to reduce target-vessel revascular-
ization (TVR) in STEMI, without any benefit in terms of
death and/or reinfarction, as compared to balloon angioplasty
[5,6]. However, these benefits may be reduced in unselected
STEMI patients [7]. Drug-eluting stents (DES) have been
recently introduced and several randomized trials have shown
a further significant reduction in restenosis and TVR in
elective patients, as compared to bare-metal stents (BMS) [8–
12]. However, recent concerns have emerged on the potential
higher risk of stent thrombosis with DES [13,14], that might
be even more pronounced among STEMI patients, as
suggested by a prospective registry [15–17]. The aim of the
current study was to perform a meta-analysis of randomized
trials on DES as compared to BMS in patients undergoing
primary angioplasty for STEMI.
1. Methods
1.1. Eligibility and search strategy
We obtained results from all completed, randomized
trials comparing DES vs BMS in primary angioplasty for
STEMI. The literature was scanned by formal searches of
electronic databases (MEDLINE and CENTRAL), and the
scientific session abstracts in Circulation, Journal of College
of Cardiology, European Heart Journal, and American
Journal of Cardiology from January 1990 to October 2007.
Furthermore, oral presentations and/or expert slide presenta-
tions were included (searched on the TCT (www.tctmd.
com), EuroPCR (www.europcr.com), ACC (www.acc.org),
AHA (www.aha.org), and ESC (www.escardio.org) websites
216 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222
Fig. 1. Flow diagram of the systematic overview process. RCT = randomized
controlled trials.
from January 2002 to October 2007). The following key
words were used: randomized trial, myocardial infarction,
reperfusion, primary angioplasty, stenting, DES, BMS,
sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting
stent (PES), Taxus. Inclusion criteria were: 1) randomized
treatment allocation; 2) availability of complete clinical data.
Exclusion criteria: 1) follow-up data in less than 90% of
patients; 2) ongoing studies or irretrievable data; 3) trials
including less than 50 patients. No language restrictions
were enforced.
Fig. 2. DES and mortality at 12 (upper graph) and 18⁎–24 months follow-up, with odds ratios and 95% confidence intervals (CI). The size of the data markers
(squares) is approximately proportional to the statistical weight of each trial.
1.2. Data extraction and validity assessment
Data were independently abstracted by two investigators.
In case of incomplete or unclear data on study design and
clinical outcome, authors were contacted, particularly in case
of website presentation and abstracts. Disagreements were
resolved by consensus. Data were managed according to the
intention-to-treat principle.
1.3. Outcome
Clinical endpoints were mortality, reinfarction, stent
thrombosis (defined as recurrent myocardial infarction with
angiographic proof of vessel occlusion) (Table 1) and TVR
at up to 18–24 months follow-up.
1.4. Data analysis
Statistical analysis was performed using the Review
Manager 4.27 and SPSS 11.0 statistical package. Odds ratio
(OR) and 95% confidence intervals (95% CI) were used as
summary statistics. The pooled odds ratio was calculated by
using a fixed-effect model with the Mantel–Haenszel
method and the Breslow–Day test was used to examine the
statistical evidence of heterogeneity across the studies
(p b 0.1). The DerSimonian and Laird random effect model
was additionally applied to calculate pooled odds ratio in
case of significant heterogeneity across studies. The potential
publication bias was examined by constructing a “funnel
 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222
Fig. 3. Funnel plot of all studies included in the meta-analysis (A). The
Standard Error (SE) of the ln Odds Ratio was plotted against the odds ratio
for mortality. No skewed distribution was observed, suggesting no
publication bias.
plot”, in which the standard error (SE) of the ln odds ratio
was plotted against the odds ratio (for 6 to 12 months
mortality). In addition, a linear regression approach to
measure funnel plot asymmetry was used [18].
The study was performed in compliance with the Quality
of Reporting of Meta-Analyses (QUORUM) guidelines [19].
2. Results
2.1. Eligible studies
A total of 14 randomized trials [20–33] were identified.
Three trials were excluded because of unavailability of
complete data [26,27] or inclusion of both patients with ST
Fig. 4. DES and reinfarction (REMI) at 12 (upper graph) and 18⁎–24 months follow-up, with odds ratios and 95% confidence intervals (CI). The size of the data
markers (squares) is approximately proportional to the statistical weight of each trial.
217
and non ST-segment elevation MI [33] (Fig. 1). Thus, a total
of 10 trials were finally included in the meta-analysis,
involving 3607 patients (1888 or 52.3% randomized to DES
and 1719 or 47.7% randomized to BMS). Characteristics of
the included trials are shown in Table 1. In most of trials
patients were treated with glycoprotein IIb/IIIa inhibitors and
6 to 12 months dual oral antiplatelet therapy (aspirin plus
clopidogrel).
In the trials of Di Lorenzo et al. [23] and Basel Stent
KostenEffektivitäts Trial Acute Myocardial Infarction
(BASKET-AMI) [25] patients were randomized at a ratio
of 1:1:1 to BMS, SES or PES. Routine angiographic follow-
up was performed in the Randomized Study Of Sirolimus
Eluting Stent vs Conventional Stent In Acute Myocardial
Infarction (SESAMI) trial [24], in the Single High Dose
Bolus of Tirofiban and Sirolimus Eluting Stent vs Abcix-
imab and Bare-Metal Stent in Myocardial Infarction
(STRATEGY) trial [20], the Helsinki Area Acute Myocar-
dial Infarction treatment re-evaluation — should the patient
get a drug-eluting or a normal stent (HAAMU-STENT)
study [28] and a prospective randomized controlled trial to
evaluate the efficacy of drug-eluting stents vs bare-metal
stents for the treatment of acute myocardial infarction
(MISSION trial) [29], The Drug Elution and Distal
Protection in ST-elevation Myocardial Infarction (DEDICA-
TION) study [32], Single-center randomized evaluation of
paclitaxel-eluting vs conventional stent in acute myocardial
infarction (SELECTION) [30] as well as in a subgroup of
patients in the Trial to Assess the Use of Cypher Stent in
Acute Myocardial Infarction Treated with Balloon Angio-
plasty (TYPHOON) trial [22].
218 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222

Fig. 5. DES and in-stent thrombosis at 12 (upper graph) and 18⁎–24 months follow-up, with odds ratios and 95% confidence intervals (CI). The size of the data
markers (squares) is approximately proportional to the statistical weight of each trial.

2.2. Clinical endpoints mortality was observed between DES and BMS (4.17% vs
4.4%, OR [95% CI] = 0.91 [0.66, 1.27], p = 0.59 (fixed-effect
2.2.1. Mortality model), p heterogeneity = 0.49). No difference in mortality
A total of 152 patients had died at 1 year follow-up was observed between DES and BMS in both trials with
(4.2%). As depicted in Fig. 2, no significant difference in (4.3% vs 3.6%, OR [95% CI] = 1.15 [0.70, 1.89]), p = 0.57)

Fig. 6. DES and target-vessel revascularization (TVR) at 12 (upper graph) and 18⁎–24 months follow-up, with odds ratios and 95% confidence intervals (CI).
The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. #Target-lesion revascularization.
 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222
or without (3.9% vs 5.1%, OR [95% CI] = 0.74 [0.48, 1.15],
p = 0.15) 1-year prescription of dual oral antiplatelet therapy
(p interaction = 0.19).
Visual analysis of the funnel plot (Fig. 3), and the
mathematical estimate of the asymmetry of this plot provided
by a linear regression approach (p = 0.41) did not show a
publication bias.
As shown in Fig. 2, similar findings were observed at
longer follow-up (between 18 and 24 months) available
from 4 trials, including 1178 patients (6.1% vs 9.2%, OR
[95% CI] = 0.66 [0.43, 1.03], p = 0.07 (fixed-effect model),
p heterogeneity = 0.9).
2.2.2. Reinfarction
Reinfarction was observed in a total 117 patients (3.3%).
As shown in Fig. 4, no significant difference in reinfarction
was noted between DES and BMS at 1 year follow-up (3.1%
vs 3.4%, OR [95% CI] = 0.86 [0.59, 1.25], p = 0.43 (fixed-
effect model), p heterogeneity = 0.6). No difference in
reinfarction was observed between DES and BMS in both
trials with (3.7% vs 4.1%, OR [95% CI] = 0.85 [0.52, 1.39],
p = 0.52) or without (3% vs 2.9%, OR [95% CI]=1.03 [0.60,
1.78], p=0.91) 1-year prescription of dual oral antiplatelet
therapy (p interaction=0.54).
As shown in Fig. 4, these results were confirmed at longer
follow-up (between 18 and 24 months) available from 4
trials (4.7% vs 4.4%, OR [95% CI] = 0.97 [0.55, 1.71],
p = 0.92 (fixed-effect model), p heterogeneity = 0.98).
2.2.3. Stent thrombosis
Stent thrombosis was observed in a total of 69 patients
(1.9%). As shown in Fig. 5, a similar outcome was observed in
terms of stent thrombosis between DES and BMS at 12 months
follow-up (1.6% vs 2.2%, OR [95% CI] = 0.76 [0.47, 1.23],
p = 0.27 (fixed-effect model), p heterogeneity = 0.94). No
difference in in-stent thormbosis was observed between DES
and BMS in both trials with (1.1% vs 2.1%, OR [95% CI] =
0.55 [0.25, 1.21], p = 0.14) or without (2.1% vs 2.3%, OR
[95% CI] = 0.94 [0.51, 1.73], p = 0.83) 1-year prescription of
dual oral antiplatelet therapy (p interaction = 0.26).
Similar results were observed at longer follow-up
(between 18 and 24 months) available from 4 trials (1.1%
vs 1.9%, OR [95% CI] = 0.55 [0.21, 1.46], p = 0.23 (fixed-
effect model), p heterogeneity = 0.74) (Fig. 5).
2.2.4. Target-vessel revascularization
By 12 months follow-up, a total of 311 patients (8.6%)
underwent repeat intervention of the target vessel. As shown
in Fig. 6, DES were associated with a significant reduction in
TVR (5.0% vs 12.6%, OR [95% CI] = 0.36 [0.28, 0.47],
p b 0.0001 (fixed-effect model), p heterogeneity = 0.57).
A sensitivity analysis was performed to investigate the
impact of routine angiographic follow-up on the benefits in
terms of TVR. No interaction (p = 0.14) was observed
between trials with (4.9% vs 13.8%, OR [95% CI] = 0.32
[0.24–0.44], p b 0.0001) or without (4.8% vs 9.3%, OR
219
[95% CL] = 0.46 [0.29–0.73], p = 0.002] routine angio-
graphic follow-up (Table 1).
The benefits in terms of TVR persisted at longer follow-
up (between 18 and 24 months) available from 4 trials (5.9%
vs 13.5%, OR [95% CI] = 0.40 [0.26, 0.60], p b 0.0001
(fixed-effect model), p heterogeneity = 0.15) (Fig. 6).
3. Discussion
The main finding of this meta-analysis is that, among
STEMI patients undergoing primary angioplasty, DES
compared to BMS are associated with a significant reduction
in TVR at 1 and 2 years follow-up, with no apparent safety
concerns when compared to BMS.
For many years stenting had been avoided in the setting of
AMI, because the implantation of a metallic device within a
thrombotic environment, such as that of a plaque disruption
resulting in myocardial infarction, would be likely to
precipitate stent thrombosis with resultant vessel occlusion.
Vigorous anti-coagulation, necessary to avoid stent throm-
bosis, exposed the patient to the risk of bleeding and vascular
complications [34]. However, following improvements in-
stent deployment techniques and advances in antiplatelet
therapy [4,35,36], numerous studies and randomized trials
have demonstrated the safety and efficacy of stenting in the
setting of STEMI [5–7,37–40].
Previous meta-analyses in patients undergoing primary
PCI have shown the benefits of stenting compared to
balloon angioplasty alone in terms of reducing TVR, though
no definite impact on death and reinfarction was present
[5,6]. However, restenosis rates after BMS in STEMI
patients are still high, especially in unselected patients with
complex lesion morphology [41]. Several randomized trials
have shown that, among elective patients, DES are as-
sociated with a significant reduction in restenosis and TVR
[8–12]. However, recent concerns have emerged regarding
an increased risk of late thrombosis stent associated with
DES [13–17]. As most episodes of stent thrombosis result in
myocardial infarction, this increase with DES may impact
mortality, particularly after primary angioplasty, as reinfarc-
tion is a major determinant of survival [42,43]. In a recent
prospective multicenter primary angioplasty registry (PRE-
MIER), the use of DES rather than BMS was associated
with higher risk of mortality within the first 6 months
(presumably due to higher stent thrombosis), particularly in
case of early discontinuation of double oral antiplatelet
therapy [15,16]. In fact, differently from elective patients, it
may be difficult to forecast future long-term patients' com-
pliance at the time of intervention among STEMI patients
[15]. In or meta-analysis we did not observed a significant
interaction between the duration of double antiplatelet
therapy and the risk of death, reinfarction and in-stent
thrombosis.
Several randomized trials have been conducted so far in
STEMI [20–33]. Valgimigli et al. [20] compared SES plus
tirofiban to the bare-metal Bx Velocity plus abciximab in 175
220 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222
STEMI patients. At 8 months follow-up, SES was associated
with a significant reduction in TVR (7% vs 20%, p = 0.01),
with a similar outcome in terms of death (2% vs 3%, p = NS),
reinfarction (1% vs 3%, p = NS) and stent thrombosis (0 vs
2%, p = NS). The benefits from SES in terms of reducing
clinical and angiographic restenosis without an increase in
death or MI have been confirmed in subsequent moderate
sized randomized trials such as the TYPHOON and SESAMI
trials [22,24].
In the Paclitaxel-Eluting Stent vs Conventional Stent in
Myocardial Infarction with ST-segment Elevation (PAS-
SION) trial [21], Laarman et al. compared PES vs Express
stent in 619 STEMI patients. Despite the safety of PES in
terms of death (4.6% vs 6.5%, p = NS) and stent thrombosis
(1% vs 1%, p = NS) at 1-year follow-up, as compared to
BMS, only a weak trend was present toward a reduction in
target-lesion revascularization (5.3% vs 7.8%, p = NS). The
relatively less favorable outcomes of PES in this trial
compared to SES in the previous trials may relate either to
the less marked reduction of neointimal hyperplasia with
paclitaxel compared to sirolimus, or a better outcome with
the control stent in the PASSION trial compared to the Bx
Velocity in the SES trials. Also of note, routine angiographic
follow-up was not performed in the PASSION trial.
Recent meta-analyses on DES in primary angioplasty
[44,45] have shown a significant reduction in TVR,
without any difference in terms of death and reMI.
However, they failed to include all current available trials
and did not evaluate the impact of the duration of dual
antiplatelet therapy. In our meta-analysis, including 11
randomized trials, the benefits and the safety of DES in
STEMI were confirmed at a relatively long-term follow-up
(up to 2 years). In addition, despite the reported association
between premature discontinuation of dual antiplatelet
therapy and the risk of in-stent thrombosis after DES
implantation [13–16], we did not find any impact of the
duration of clopidogrel prescription on the benefits from
DES.
Even though we did not observe a significant hetero-
geneity between trials with or without routine angiographic
follow-up, further studies are required to determine the
extent to which the benefit of DES compared to BMS in
reducing TLR and TVR in patients undergoing primary PCI
is modulated by routine angiographic follow-up [46].
Moreover, two smaller randomized trials, which included
180 and 217 patients, respectively, compared SES and PES
vs BMS in this setting and similar TVR rates were noted
between PES and SES groups [23,25].
Large randomized trials, with longer follow-up data are
certainly needed to further investigate these observations and
the long-term safety of DES in primary angioplasty. In this
regard, important information is expected to be derived from
ongoing trials, such as the MULTISTRATEGY [47] and
particularly the HORIZONS-AMI trial [48], in which more
than 3000 patients with STEMI undergoing primary PCI
have been randomized to PES vs BMS.
4. Limitations
The patients enrolled in the current randomized trials
have for the most part been highly selected, and thus the
conclusion of this meta-analysis cannot be extended to all
patients undergoing primary angioplasty for STEMI.
Furthermore, both visual and mathematical analysis cannot
completely exclude any publication bias. We were not able
to obtain complete data from two randomized trials
[26,27]. The results of the current analysis mostly apply
only to SES and PES, as randomized studies in STEMI
have not yet been performed with newer emerging DES.
Several reports have shown a higher risk of subacute
thrombosis up to 2–3 years after DES implantation. In the
large prospective cohort study by Largerqvist et al. [49],
including up to 20,000 patients, drug-eluting stents were
associated with an increased rate of death, as compared
with bare-metal stents. This trend appeared after 6 months,
when the risk of death was 0.5 percentage point higher and
a composite of death or myocardial infarction was 0.5 to
1.0 percentage point higher per year as compared to BMS.
Thus, larger randomized trials with longer-term follow-up
are certainly required to confirm the safety profile of DES
in STEMI.
Even though websites screening for slide presentations
might limit a possible publication bias, it might introduce
other forms of bias due to potentially incomplete follow-up
data at the time of data presentation. However, complete
follow-up data were available from all trials included in the
current meta-analysis.
Finally, the larger rate of target-vessel revascularization in
the BMS group, which censors patients in this group, might
have introduced a bias against DES [50].
5. Conclusions
This meta-analysis of 3607 patients from 11 randomized
trials shows that among selected STEMI patients undergoing
primary angioplasty, SES and PES, as compared to BMS, are
associated with a significant reduction in TVR at 1 and
2 years follow-up, with no apparent safety concerns having
emerged. However, due to the relatively short follow-up
period analyzed, further trials with long-term follow-up up to
3 to 5 years, are certainly needed to further support the safety
of DES in primary angioplasty.
Conflict of interest
Dr. Spaulding: consulting or lecture fees from Cordis,
Boston, Abbott, Lilly and Pfizer); Dr. Stone's: Consultant
to and lecture fees from Boston Scientific and Abbott
Vascular; Equity in Xtent and Devax, and Board of directors
for Devax; Dr. Laarman: advisory board of Boston
Scientific and lecture fees from Cordis, Johnson & Johnson,
and Medtronic; Dr. Dirksen: lecture fees from Boston
Scientific.
 G. De Luca et al. / International Journal of Cardiology 133 (2009) 213–222
Acknowledgments
Drs De Luca and Suryapranata had full access to all the data in
the study and take responsibility for the integrity of the data and the
accuracy of the data analysis.
This study has no financial support.
All authors declare that they participated in the study and that
they have seen and approved the final version.
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