A Comparison of Abciximab and Small-Molecule
Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing
Primary Percutaneous Coronary Intervention
A Meta-Analysis of Contemporary Randomized Controlled Trials
Hitinder S. Gurm, MD; Umesh Tamhane, MD; Pascal Meier, MD; P. Michael Grossman, MD;
Stanley Chetcuti, MD; Eric R. Bates, MD
Downloaded from http://circinterventions.ahajournals.org/ by guest on June 17, 2017
Background—Current guidelines recommend abciximab as the preferred agent for patients undergoing primary
percutaneous coronary intervention, yet small-molecule glycoprotein IIb/IIIa inhibitors are more commonly used in
clinical practice. The objective of our meta-analysis was to evaluate for differences in clinical outcome between
small-molecule glycoprotein IIb/IIIa inhibitors and abciximab in patients with ST-segment elevation myocardial
infarction undergoing primary percutaneous coronary intervention.
Methods and Results—Five randomized trials (n⫽2138 patients) comparing tirofiban or eptifibatide with abciximab as an
adjunctive therapy to primary percutaneous coronary intervention were included in this meta-analysis. Summary odds
ratios (ORs) for 30-day death, reinfarction, and major bleeding were calculated using random- and fixed-effect models.
There were no differences in 30-day mortality (1.9% for small molecule versus 2.3% for abciximab; OR, 0.84; 95% CI,
0.46 to 1.55; P⫽0.58), reinfarction (1.3% versus 1.2%; OR, 1.22; 95% CI, 0.51 to 2.91; P⫽0.69), or major bleeding
(1.7% versus 1.3%; OR, 1.21; 95% CI, 0.58 to 2.49; P⫽0.61) between the 2 adjunctive strategies. Similarly, there was
no significant difference in the incidence of death (3.9% versus 5%; OR, 0.77; 95% CI, 0.41 to 1.46; P⫽0.43) or
reinfarction on follow-up at 8 months between small-molecule glycoprotein IIb/IIIa inhibitors and abciximab.
Conclusion—In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial
infarction, no difference in outcome could be identified in patients treated with small-molecule glycoprotein IIb/IIIa
inhibitor or abciximab. (Circ Cardiovasc Intervent. 2009;2:230-236.)
Key Words: primary PCI 䡲 ST elevation MI 䡲 abciximab 䡲 tirofiban 䡲 eptifibatide
P
rimary percutaneous coronary intervention (PCI) is the
preferred reperfusion strategy in ST-segment elevation
myocardial infarction (STEMI).1 The optimal procedural
anticoagulation strategy in patients undergoing primary PCI,
however, remains to be defined. Although the current guidelines support the use of abciximab in patients undergoing
primary PCI, a number of patients are treated with smallmolecule glycoprotein (GP) IIb/IIIa agents or without GP
IIbIIIa inhibitors in “real-world” clinical practice for various
reasons.2,3 The absolute magnitude of survival benefit demonstrated in association with abciximab is small and somewhat controversial.4 – 6 Further, eptifibatide or tirofiban—
small-molecule agents that share some but not all
pharmacological properties with abciximab—are significantly less expensive and more widely available in many
hospitals. Observational data suggest similar outcomes in
patients undergoing primary PCI who are treated with smallmolecule GP IIb/IIIa inhibitors compared with those treated
with abciximab.2,7,8
Clinical Perspective on p 236
Small randomized trials evaluating predominantly angiographic end points have demonstrated no difference between
small-molecule GP IIb/IIIa inhibitors and abciximab in patients undergoing primary PCI, although none of these trials
were powered for clinical end points. We accordingly performed a meta-analysis of the randomized trials comparing
abciximab with small-molecule GP IIb/IIIa inhibitors dosed
per current recommendations in patients undergoing contemporary primary PCI.
Methods
We performed a computerized search to identify relevant articles
from 2000 through October 30, 2008, in the MEDLINE, Embase, ISI
Web of Knowledge, Current Contents, International Pharmaceutical
Abstracts databases, and the Cochrane Central Register of Controlled
Trials. We combined exploded medical subject headings and keyword searches for abciximab, tirofiban, eptifibatide, and primary
PCI. Abstract lists from the 2008 scientific meetings of the American
Received November 26, 2008; accepted April 17, 2009.
From the Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich.
Correspondence to Hitinder S. Gurm, MD, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan
Cardiovascular Center, 2A394, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5853. E-mail [email protected]
© 2009 American Heart Association, Inc.
Circ Cardiovasc Intervent is available at http://circinterventions.ahajournals.org
230
DOI: 10.1161/CIRCINTERVENTIONS.108.847996
Gurm et al
Table 1.
Small-Molecule GP IIb/IIIa Inhibitors in Primary PCI
231
Baseline Characteristics of Studies Included in the Meta-Analysis
Danzi et al, 2004
Small
Molecule
Valgimigli et al, 2005
EVA-AMI, 2007
Small
Molecule
Bolus 25
␮g/kg⫹18-h
infusion of
0.15 ␮g
kg⫺1 min⫺1
Bolus 0.25
mg/kg⫹12-h
infusion of
0.125 ␮g kg⫺1
min⫺1
Bolus 25
␮g/kg ⫹18- to
24-h infusion
of 0.15 ␮g
kg⫺1 min⫺1
Bolus 0.25
mg/kg⫹12-h
infusion of
0.125 ␮g kg⫺1
min⫺1
No. patients in
each arm
50
50
87
88
Male, %
82
84
77
69
76.1
80.1
73
79
71.8
78.9
Mean age, y
61
59
62*
63*
61.3
60.5
63.3
64.4
65
63.4
17.3
Agent and
dose
Tirofiban
Tirofiban
Abciximab
Small
Molecule
Bolus 0.25
mg/kg⫹12-h
infusion of
0.125 ␮g kg⫺1
min⫺1
Bolus 0.25
mg/kg⫹18-to
24-h infusion
of 0.15 ␮g
kg⫺1 min⫺1
FATA, 2008
Abciximab
Abciximab
Small
Molecule
MULTISTRATEGY, 2008
Eptifibatide
Abciximab
Small
Molecule
Bolus 0.25
mg/kg⫹12-h
infusion of
0.125 ␮g kg⫺1
min⫺1
Bolus 25
␮g/kg⫹18-h
infusion of
0.15 ␮g
kg⫺1 min⫺1
Tirofiban
Double bolus
(180 ␮g/kg
within 10
min)⫹24-h
infusion (2.0
␮g kg⫺1
min⫺1)
226
203
Abciximab
Tirofiban
372
372
Bolus 0.25
mg/kg⫹12-h
infusion of 0.125
␮g kg⫺1 min⫺1
351
341
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Diabetes, %
18
16
17
12
14.6
17.4
13.2
15.9
18.8
Prior MI, %
NA
NA
13
9
8.4
8.5
8.1
7.3
6
2.6
Anterior MI, %†
42
32
49
41
43.4
45.3
44.7
46.4
46.3
214
200
180*
180*
263
254
101‡
30
30
240
240
180
180
240
Mean
symptom to
Balloon time,
min
Follow-up
duration, d
43
96‡
240
744
160*
30
30
Total No.
patients
100
175
Primary
outcome
Infarct-zone wall motion score
index (IZWMSI)
Composite of death, MI, stroke,
binary stenosis
STR ⬎70% at 60 min
STR ⱖ50% at 90 min MACE
STR ⱖ70% at 90 min
Definition of
major bleeding
Thrombolysis in myocardial
infarction (TIMI) major criteria
TIMI major criteria
NA
TIMI major criteria
Combination of TIMI and global
use of strategies to open occluded
coronary arteries (GUSTO)
definitions
Definition of
minor bleeding
TIMI minor criteria
TIMI minor criteria
NA
TIMI minor criteria
Local hematoma and any other
clinically relevant bleeding that did
not meet criteria for severity
Symptoms consistent with acute
MI ⱖ30 min and ST-segment
elevation in 2 contiguous leads
or LBBB
Chest pain ⬎30 min and ST
elevations ⱖ1 mm in 2 or more
contiguous ECG leads or new
onset LBBB
Chest pain ⬎20 min and ST
elevations in 2 contiguous leads
(ⱖ2 mm in precordial, ⬎1 mm
in limb lead)
Chest pain ⬎30 min and ST
elevations ⱖ1 mm in 2 or more
contiguous ECG leads or New
onset LBBB
Chest pain ⬎20 min and
ST-segment elevation of at least
0.1 mV in 2 or more contiguous
ECG leads
Definition of
MI
429
153*
692
MACE indicates major adverse cardiac events (death, MI, TVR); LBBB, left bundle-branch block; STR, ST-segment resolution; TIMI, Thrombolysis in Myocardial
Infarction.
*Median.
†In the studies with missing anterior MI rate, patients with left anterior descending artery as culprit artery were considered to have anterior MI.
‡The trial provided median values for patients that were randomized in a factorial design to bare metal or drug eluting stents. The mean value for the medians
is provided.
College of Cardiology, the European Society of Cardiology, and the
Transcatheter Cardiovascular Therapeutics and published review
articles, editorials, and internet-based sources of information on trials
of interest, including www.tctmd.com and www.theheart.org, were
also reviewed.
A study was included if it randomized patients undergoing
primary PCI for STEMI to abciximab or a small-molecule GP
IIb/IIIa inhibitor in a randomized fashion and provided data on at
least 1 outcome of interest over a follow-up period of at least 30
days.
Definitions and Outcome Measures
The end points of interest were death, reinfarction, and bleeding at 30
days. Medium-term mortality and reinfarction were also pooled.
Death was defined as mortality from any cause. Target vessel
revascularization (TVR) was defined as surgical or percutaneous
revascularization of the infarct-related artery. Reinfarction and
bleeding (major and minor) were defined slightly differently by each
trial (Table 1). We used the study defined end points for the analysis.
In a secondary analysis, we evaluated procedural angiographic
outcome (thrombolysis in myocardial infarction-3 flow and ST
resolution). Data were collected independently by 2 reviewers (U.T.
and P.M.) and disagreements were resolved by consensus. Baseline
demographic, clinical, and angiographic outcomes were recorded for
each study. We also assessed trial quality by evaluating specific
elements of study design (ie, concealment of allocation during
randomization, intention to treat analysis, and blinded assessment of
outcome measures) but did not use a quality score given the
limitations inherent to such an approach.9 Given the small number of
trials available, we did not exclude any trial based on study
characteristics.
Statistical Analysis
From each trial, results were organized into a 2-by-2 table to permit
calculation of effect sizes for small-molecule agents and abciximab.
All data were pooled at the study level, because patient level data
were not available. Such pooling has been previously demonstrated
to be valid for estimating pooled treatment effect.10 All analyses
232
Circ Cardiovasc Intervent
June 2009
Table 3. Summary ORs for Death, TVR, Reinfarction, and
Major and Minor Bleedings (All Events at 30 Days) Generated
Using Fixed-Effect and Random-Effect Models
Summary OR (95% CI)
Fixed Effect
Model
Random Effect
Model
Heterogeneity
P
Death
0.84 (0.46 to 1.55)
0.84 (0.46 to 1.55)
0.56
TVR
0.95 (0.47 to 1.91)
0.95 (0.44 to 2.07)
0.33
Reinfarction
1.22 (0.51 to 2.91)
0.94 (0.27 to 3.21)
0.21
Major bleeding
1.21 (0.58 to 2.49)
1.21 (0.58 to 2.49)
0.43
Minor bleeding
0.75 (0.48 to 1.17)
0.75 (0.48 to 1.17)
0.82
End Point
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IIb/IIIa receptor inhibitors versus abciximab. Of these, 4 trials
comparing tirofiban with abciximab had been published in
peer-reviewed journals.15–18 All these trials used the currently
recommended higher loading dose (25 ␮g/kg) of tirofiban.
One trial, EVA-AMI,19 which compared eptifibatide with
abciximab, was presented at American Heart Association
Scientific Sessions 2007, and the information was obtained
from www.crtonline.org. A total of 2138 patients from 5
randomized, controlled trials constituted our final study
population (Figure 1). The characteristics of included trials
and study population are shown in Table 1. The raw clinical
events in each arm across the trials are listed in Table 2.
Summary ORs for death, TVR, reinfarction, and major and
minor bleedings (all events at 30 days) generated using fixedand random-effect models are shown in Table 3.
There was no difference in angiographic outcome between
the 2 groups. Thrombolysis in myocardial infarction-3 flow
was achieved in both groups in a large proportion of patients
with no difference between the 2 groups (89% with smallmolecule GP IIb/IIIa inhibitor versus 90% with abciximab;
OR, 0.96; 95% CI, 0.72 to 1.27; P⫽0.77). Similarly no
difference in ST resolution was noted between the 2 groups
(72% with small-molecule GP IIb/IIIa inhibitor versus 71%
with abciximab; OR, 1.04; 95% CI, 0.84 to 1.29; P⫽0.71).
Figure 1. Flow diagram depicting the selection of studies
included in the meta-analysis.
were performed on an intention-to-treat basis. When the outcome did
not occur in 1 or both groups, continuity correction was performed.11
We used fixed- and random-effect models to produce across-study
odds ratios (ORs). Because both models yielded similar results, the
fixed-effect models are preferentially reported. Cochran Q-test was
used to assess heterogeneity. To assess the effect of individual
studies on the summary estimate of effect, we did an influence
analysis, in which the pooled estimates were recalculated omitting 1
study at a time.
We also calculated fail-safe N, ie, the number of studies required
to nullify the significant differences in mortality between the 2
groups using the method of Rosenberg and Orwin.12,13 All analyses
were performed using Comprehensive Meta-Analysis software (version 2.0, Biostat, Englewood, NJ).
Results
Clinical End Points
Data on 30-day mortality were available in 2138 patients
(100%). Mortality in the trials ranged from 0% to 3.5% in the
small-molecule arm and 0% to 3.5% in the abciximab arm.
There were no differences in 30-day mortality between the 2
groups (1.9% for small molecule versus 2.3% for abciximab;
OR, 0.84; 95% CI, 0.46 to 1.55; P⫽0.58; Figure 2). None of
the studies influenced the results, such that the results would
A total of 268 citations published between January 2000 and
October 2008 were screened. Studies comparing smallmolecule GP IIb/IIIa receptor inhibitors with abciximab
without randomization were excluded.2,7,8 One randomized
trial was excluded, because it did not provide angiographic or
mortality data.14 Our meta-analysis, thus, included 5 trials
that randomized patients with STEMI to small-molecule GP
Table 2.
Clinical Events in Each Arm Across the Trials in the Meta-Analysis
Death
Study/Author
Small Molecule
Reinfarction
Abciximab
Major Bleeding
Small Molecule
Abciximab
Small Molecule
Abciximab
NA
NA
NA
NA
3 (3.4)
1 (1.1)
3 (3.4)
1 (1.1)
7 (3.5)
0 (0)
3 (1.5)
6 (2.7)
4 (1.1)
9 (2.4)
10 (2.7)
5 (1.3)
7 (2)
5 (1.5)
2 (0.6)
1 (0.3)
Danzi et al, 2004
0 (0)
0 (0)
Valgimigli et al, 2005
2 (2.3)
EVA-AMI, 2007
8 (3.5)
MULTISTRATEGY, 2008
FATA, 2008
NA indicates not applicable.
TVR
Small Molecule
Abciximab
0 (0)
0 (0)
3 (3.4)
1 (1.1)
2 (2.3)
8 (4)
4 (1.8)
0 (0)
8 (2.2)
6 (1.6)
9 (2.4)
6 (1.6)
3 (0.9)
0 (0)
5 (1.4)
6 (1.8)
Gurm et al
Small-Molecule GP IIb/IIIa Inhibitors in Primary PCI
233
Figure 2. The forest plot of ORs of 30-day mortality. Sizes of data markers are proportional to the weight of each study in the metaanalysis. The study by Danzi et al15 had no events in either arm and is, thus, not represented in the forest plot. Horizontal bars indicates 95% CIs; SM GPI, small-molecule GP IIb/IIIa receptor inhibitor.
have changed significantly; the influence analysis omitting 1
study at a time consistently showed no difference in survival
of patients treated with either strategy (data not shown).
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TVR and Reinfarction
Data on 30-day TVR were available in 2038 patients (95%).
The incidence of TVR ranged from the 0.9% to 2.7% in the
small-molecule arm and 0% to 4% in the abciximab arm.
Overall, TVR occurred in 18 patients (1.7%) in the smallmolecule GP IIb/IIIa receptor inhibitors group and 17 patients
(1.7%) in the abciximab group. There was no significant
difference in the likelihood of TVR in patients treated with
small molecules as compared with those treated with abciximab (OR, 0.95; 95% CI, 0.47 to 1.91; P⫽0.89).
Data on 30-day reinfarction were available in 2038 patients
(95%). The incidence of reinfarction ranged from the 0% to
2.7% in the small-molecule arm and 0.3% to 3.4% in the
abciximab arm. There were no significant differences in the
incidence of 30-day reinfarction between the 2 groups (1.3%
for small molecule versus 1.2% for abciximab; OR, 1.22;
95% CI, 0.51 to 2.91; P⫽0.69).
1.21; 95% CI, 0.58 to 2.49; P⫽0.61; Figure 3). Similarly
there was no difference in minor bleeding between the 2
groups (3.4% with small-molecule GP IIb/IIIa inhibitor
versus 4.5% with abciximab; OR, 0.75; 95% CI, 0.48 to 1.17;
P⫽0.21).
Data on stroke were available from 2 trials. Only 1 stroke
was reported in the abciximab arm whereas no stroke was
reported in patients randomized to small-molecule GP IIb/IIIa
arm (OR, 0.29; 95% CI, 0.01 to 7.28; P⫽0.45).19
Intermediate-Term Follow-Up
Data on 8-month mortality were available in 919 patients
(43%). There was no significant difference in the incidence of
death (3.9% versus 5%; OR, 0.77; 95% CI, 0.41 to 1.46;
P⫽0.43) on follow-up at 8 months between small-molecule
GP IIb/IIIa inhibitors and abciximab.
Data on 8-month reinfarction were available from 2 trials
in 919 patients (43%). The reinfarction rates on 8-month
follow-up did not differ between the small-molecule group
(4.8%) and the abciximab group (4.6%) (OR, 1.05; 95% CI,
0.57 to 1.96; P⫽0.86).
Safety End Points
Publication Bias
Data on major bleeding were available in 2138 patients
(100%). Major bleeding in the trials ranged from 0% to 2.4%
in the small-molecule arm and 0% to 2.3% in the abciximab
arm. In the pooled estimate, major bleeding occurred in 19
patients (1.7%) in the small-molecule GP IIb/IIIa receptor
inhibitors group and 14 patients (1.3%) in the abciximab
group. There was no difference in major bleeding between
patients treated with small-molecule GP IIb/IIIa receptor
inhibitors compared with those treated with abciximab (OR,
There was no evidence of publication bias for any of the end
points studied (Figure 4, funnel plot for mortality). The
Eggers test of intercept suggested no evidence for publication
bias for mortality (1-tailed P⫽0.35) or any of the other end
points. The classic fail-safe number was not relevant, because
there was no difference in any of the end points between the
2 agents. Calculations of Orwin’s fail-safe N suggested that 9
studies favoring abciximab with a mean OR of 2 would be
needed to bring the combined OR ⬎1.5.
Figure 3. The forest plot of ORs of major bleeding. Sizes of data markers are proportional to the weight of each study in the metaanalysis. The study by Danzi et al15 had no events in either arm and is, thus, not represented in the forest plot. Horizontal bars indicate
95% CIs; SM GPI, small-molecule GP IIb/IIIa receptor inhibitor.
234
Circ Cardiovasc Intervent
June 2009
Figure 4. Funnel plot for the end point of
30-day death. The studies are distributed
symmetrically about the combined effect
size, suggesting no publication bias.
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Discussion
Our data suggest that the use of tirofiban or eptifibatide is
associated with a clinical outcome similar to that associated
with the more widely evaluated agent abciximab in patients
undergoing primary PCI. No difference in outcome of patients treated with the 2 classes of drugs could be identified in
the early or medium-term outcome with respect to mortality,
reinfarction, or bleeding.
Mechanical reperfusion is currently the pre-eminent reperfusion therapy for acute STEMI. Although stent-based PCI
has been established as the standard for primary PCI, the
optimal pharmacological regimen for these patients is only
now being scrutinized. In contrast to studies of fibrinolytic
agents, most placebo-controlled trials evaluating GP IIb/IIIa
inhibitors in primary PCI for acute STEMI have been small
and underpowered to demonstrate a survival benefit. Within
this small body of data, most studies have evaluated the role
of abciximab. The clinical support for the use of abciximab is
derived from a meta-analysis performed by De Luca et al,4 in
which the use of abciximab was associated with a significant
reduction in 30-day mortality, reinfarction, and long-term
mortality without an increase in bleeding events. A trend
toward reduction in early and late mortality with abciximab
was also observed by Montalescot et al in a patient-level
meta-analysis of patients undergoing stenting for primary
PCI. The key finding of their analysis was that the use of
abciximab was associated with a 37% reduction in the
composite hazard of death or reinfarction at 3 years (HR,
0.63; 95% CI, 0.45 to 0.88; P⫽0.008).20 The placebo-based
comparative data for small-molecule GP IIb/IIIa inhibitors
are more limited and restricted to smaller trials designed to
compare upfront versus in-laboratory administration of GP
IIb/IIIa inhibitor and suggested better angiographic outcomes
with an early administration approach.21
It is somewhat surprising that despite the moderate clinical
benefits demonstrated in these trials, use of platelet GP
IIb/IIIa inhibitors is ubiquitous in patients undergoing primary PCI2 and has been considered the standard of care for
recent comparative trials.22 The use of abciximab in patients
undergoing primary PCI has a class IIa recommendation
whereas the small-molecule GP IIbIIIa inhibitors carry a class
IIb recommendations according to both the European Society
of Cardiology task force and the American College of
Cardiology/American Heart Association guidelines for the
management of patients with STEMI.1,23
In an observational study from the Blue Cross Blue Shield
of Michigan Cardiovascular Consortium (BMC2) of ⬎4100
patients undergoing primary PCI, a GP IIb/IIIa inhibitor was
used in ⬎85% with eptifibatide being the most commonly
used agent. In this observational study, no difference in any
of the safety and efficacy end points between eptifibatide and
abciximab was observed.
In the only large-scale randomized trial evaluating the
relative efficacy of tirofiban and abciximab24 for PCI, there
seemed to be a reduction in ischemic events in patients
treated with abciximab that was predominantly seen in
patients with acute coronary syndromes. The dose of tirofiban
used in this trial was lower than the currently recommended
dose and the lack of equivalent platelet inhibition with the 2
regimens has been invoked as the reason for the better
outcome with abciximab. Patients with acute STEMI were
excluded from the trial and until the completion of the trials
discussed in the current meta-analysis, there were no randomized data comparing the efficacy of different GP IIb/IIIa
inhibitors in primary PCI. All the trials included in our
meta-analysis used the currently recommended higher dose of
small-molecule GP IIb/IIIa inhibitors and this may explain
the observed lack of difference in clinical outcomes between
abciximab and small-molecule GP IIb/IIIa inhibitors in our
study.
Our data are, thus, important for many reasons. Our results
corroborate the earlier observational data demonstrating no
major difference in survival of patients treated with abciximab or small-molecule agents. Second, the incidence of
bleeding events in these trials was low and not influenced by
the specific agent used. Based on contemporary 30-day
outcome of patients undergoing primary PCI, a trial powered
for mortality would need to enroll ⬎10 000 patients to
Gurm et al
Small-Molecule GP IIb/IIIa Inhibitors in Primary PCI
demonstrate superiority of 1 agent over another. Given the
lack of major differences in observational data, cost of large
trials and market realities, and the results of this meta-analysis, such a trial is unlikely to be performed.
3.
Limitations
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Our meta-analysis is subject to the limitations inherent to all
meta-analyses, which include publication bias (although
tested nonsignificant in our study) and the difficulties in
comparing the results because of the different study populations, study designs, and reporting methods as well as the
absence of individual patient data, which prohibits adjustment
for confounding factors.25 Further, we did not have data on
long-term outcome. Previous observational studies have detected differences in long term but not in short-term outcome
of patients treated with GP IIb/IIIa inhibitors versus those
treated with heparin only.26 It is possible that the enhanced
microcirculatory improvement achieved with these drugs
impacts long-term survival. Our study cannot detect differences in long-term outcome, because these data were not
available. Further, we combined data from 4 trials of tirofiban
with 1 trial of eptifibatide. Although there was no statistical
heterogeneity in our analysis, there are no direct comparative
data to support (or refute) clinical equivalence of the 2 agents.
The summary ORs for intermediate-term outcome are limited
because these calculations ignore time to event, and hazard
ratios cannot be calculated in the absence of patient-level
data.
Finally, the event rates in this meta-analysis are very low
suggesting enrollment of low-risk patients and a possible
Type II error cannot be excluded. These rates are comparable
with the rates reported in the abciximab group in the
meta-analysis of De Luca et al (30-day mortality 2.4%)
suggesting similarity of patients enrolled and are thus likely
extant.
Conclusions
Among patients undergoing contemporary primary PCI, there
was no difference in the clinical outcome of patients treated
with small-molecule GP IIb/IIIa inhibitors or abciximab. Our
findings provide further support for the widespread current
use of small-molecule GP IIb/IIIa inhibitors in patients
undergoing primary PCI.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Acknowledgments
We are grateful to Ms Dawn Ambs for help with formatting and
submission of this manuscript.
17.
Disclosures
None.
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CLINICAL PERSPECTIVE
Although current guidelines support the use of abciximab in patients undergoing primary percutaneous coronary
intervention, small-molecule glycoprotein IIb/IIIa inhibitors are more commonly used in contemporary clinical practice.
Small, randomized trials evaluating predominantly angiographic end points have demonstrated no difference between
small-molecule glycoprotein IIb/IIIa inhibitors and abciximab in patients undergoing primary percutaneous coronary
intervention, although none of these trials were powered for clinical end points. We report a systematic evaluation of
clinical outcomes of studies comparing small-molecule glycoprotein IIb/IIIa inhibitors with abciximab in patients
undergoing primary percutaneous coronary intervention. Our meta-analysis included 2138 patients from 5 randomized
controlled trials. There were no differences in 30-day mortality (odds ratio, 0.84; P⫽0.58), reinfarction (odds ratio, 1.22;
P⫽0.69), or major bleeding (odds ratio, 1.21; P⫽0.61) between the 2 adjunctive strategies. Similarly, there was no
significant difference in the incidence of death (odds ratio, 0.77; P⫽0.43) or reinfarction on intermediate-term follow-up.
Our findings provide further support for the widespread current use of small-molecule glycoprotein IIb/IIIa inhibitors in
patients undergoing primary percutaneous coronary intervention.
Downloaded from http://circinterventions.ahajournals.org/ by guest on June 17, 2017
A Comparison of Abciximab and Small-Molecule Glycoprotein IIb/IIIa Inhibitors in
Patients Undergoing Primary Percutaneous Coronary Intervention: A Meta-Analysis of
Contemporary Randomized Controlled Trials
Hitinder S. Gurm, Umesh Tamhane, Pascal Meier, P. Michael Grossman, Stanley Chetcuti and
Eric R. Bates
Circ Cardiovasc Interv. 2009;2:230-236; originally published online April 21, 2009;
doi: 10.1161/CIRCINTERVENTIONS.108.847996
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