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150 Part II / GPIIb/IIIa Blockade During Coronary Intervention
with the 0.15 µg/kg/min dose. Four hours after cessation of the infusion, the IPA was <50%
for all three dosing regimens (Fig. 5). Heparin alone did not affect the extent of platelet
aggregation, although it did double the median bleeding time at the 2-h mark in the placebo
group. Median bleeding times in both of the high-dose tirofiban arms at 2 h exceeded 30 min.
Fig. 3. Percent inhibition of platelet aggregation induced by collagen [2 µg/mL, (Q)] and ADP [3.4
µg/mL, (●)] by MK-383. (Adapted from ref. 24, with permission.)
Fig. 4. Inhibition of platelet aggregation as a function of time following the initiation of tirofiban therapy
(■ = 5 µg/kg bolus + 0.05 µg/kg/min infusion, ● = 10 + 0.10, F= 10 + 0.15). Data depict medians (dose
panel symbols), means (horizontal lines), 25th and 75th percentiles (boxes), and 10th and 90th percen-
tiles (whiskers). (Adapted from ref. 26, with permission.)
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Chapter 7 / Tirofiban: The RESTORE and TARGET Trials 151
Although heparin does not affect the antiplatelet activity of tirofiban, there is evidence
that administration of tirofiban with heparin results in synergistic antithrombin activity.
In a study comparing the effects on thrombin generation of abciximab versus tirofiban
during coronary intervention, both agents induced similar elevations in the activated clot-
ting time (ACT) when administered after standard heparinization (27). Furthermore, both
agents suppressed levels of F1.2, a prothrombin fragment, suggesting that their antithrom-
bin effects are caused by decreased thrombin generation. These data support the concept
that the antithrombin activity of GPIIb/IIIa inhibitors is a class effect and that ACT-guided
heparin dosing during PCI should be based on an ACT obtained following administration
of the GPIIb/IIIa inhibitor.
TIROFIBAN
IN PERCUTANEOUS CORONARY INTERVENTION
Two large-scale trials have been conducted using tirofiban in high-risk patients under-
going PCI: RESTORE (28) and TARGET (29). Dosing of tirofiban in both studies was based
on the dose-ranging study of Kereiakes et al. (26) and used the highest dosing regimen
(a 10 µg/kg bolus followed by a 0.15 µg/kg/min infusion) to ensure >90% IPA throughout
the duration of tirofiban administration.
RESTORE
STUDY DESIGN
The Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis (RESTORE)
trial was a randomized, double-blind, placebo-controlled study of tirofiban in patients
undergoing percutaneous transluminal coronary angioplasty (PTCA) or directional coro-
nary atherectomy (DCA) within 72 h of presenting with an acute coronary syndrome [unsta-
ble angina or myocardial infarction (MI)]. Unstable angina was defined as typical chest
pain occurring at rest or with minimal activity and associated with any of the following:
Fig. 5. Recovery of ex vivo platelet aggregation to 5 µM ADP as a function of time from completion
of tirofiban infusion for each of the three dosing regimens: (1) 5 µg/kg bolus + 0.05 µg/kg/min infusion,
(2) 10 µg/kg bolus + 0.10 µg/kg/min infusion, and (3) 10 µg/kg bolus + 0.15 µg/kg/min infusion.
(Adapted from ref. 26, with permission.)
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152 Part II / GPIIb/IIIa Blockade During Coronary Intervention
(1) dynamic electrocardiographic (ECG) changes consistent with myocardial ischemia;
(2) hemodynamic changes suggestive of ischemia; or (3) angiographic evidence of intra-
coronary thrombus. MI was defined as ischemic chest pain lasting >20 min with ST-T
changes or pathologic Q waves and creative kinase (CK) elevations greater than twice the
upper limit of normal (ULN) or an elevated CK-MB fraction. Notable exclusion criteria
included patients who had received thrombolytic therapy within the previous 24 h or who
were scheduled for elective coronary stent implantation. Moreover, the protocol instructed
investigators to limit the use of coronary stents to “bailout” situations such as actual or
threatened abrupt vessel closure.
All patients received 325 mg of aspirin before the procedure and weight-adjusted hep-
arin during the procedure to maintain the ACT between 300 and 400 s. Once the guidewire
had crossed the lesion, patients were randomized to tirofiban (10 µg/kg bolus over 3 min
followed by a 0.15 µg/kg/min infusion for 36 h) or matching placebo. Heparin was dis-
continued at the end of the procedure, and the arterial and venous sheaths were removed
when the ACT had fallen below 180 s.
The primary endpoint of the study was the 30-d composite of all-cause mortality, MI,
coronary artery bypass surgery (CABG), repeat target vessel PCI for recurrent ischemia,
or emergent stent implantation for actual or threatened abrupt vessel closure. The criteria
required for an MI to qualify as an event depended on the patient’s clinical diagnosis upon
enrollment in the study. In patients entering the study with unstable angina and normal
CK/CK-MB levels, the diagnosis of an MI required: (1) typical chest pain, with new ST-T
changes or new pathologic Q waves, in association with an elevated CK-MB, or (2) a CK-
MB > 3× ULN in the absence of chest pain or ECG changes. In patients enrolling within
72 h of an MI, the diagnosis of a new MI could be made if (1) the CK-MB was >3× ULN
and at least 33% > the previous nadir, or (2) the CK-MB was >3× ULN and at least 100%
greater than the previous value if that was <50% of the peak value and <2× ULN. In all
patients following hospital discharge, a new MI was defined as (1) typical chest pain with
new ST-T changes or new pathologic Q waves and an elevated CK-MB, or (2) a CK-MB
level >2× ULN unaccompanied by angina or ECG changes. Although the criteria for an MI
to qualify as an event were quite rigorous, routine surveillance for its occurrence was solely
limited to a protocol-mandated measurement of CK and CK-MB at the end of the 36-h study
drug infusion. Otherwise, cardiac enzymes were drawn only if clinically indicated to eval-
uate an episode of myocardial ischemia.
R
ESULTS
Of the 2212 patients randomized, 71 patients never received the study drug, leaving
2141 patients for inclusion in the efficacy and safety analysis. More than 70% of patients
were male, with 20% in each arm being diabetic. Most patients entered the study with a
diagnosis of unstable angina and were evenly divided among the two treatment arms. PCI
was performed as the primary reperfusion therapy for acute MI in 6% of patients in the
placebo group and 7% of patients in the tirofiban group. PTCA was the predominant inter-
ventional procedure and was performed in 93 and 92% of patients in the placebo and tirofi-
ban groups, respectively. By default, DCA was used in the remainder of patients. Single-
vessel intervention was performed in >90% of cases in both groups. Only 2% of treated
vessels were bypass grafts. Multiple lesions were treated in 20% of patients in the placebo
group and 24% of patients in the tirofiban group.
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Chapter 7 / Tirofiban: The RESTORE and TARGET Trials 153
Endpoints were evaluated at 2, 7, and 30 d with a clinical and angiographic substudy (30)
extending the follow-up to 6 mo. At 2 d, the composite endpoint was reduced from 8.7%
in the placebo group to 5.4% in the tirofiban group [relative risk reduction (RRR) = 38%,
p< 0.005], whereas at 7 d, the RRR remained statistically significant at 27% (p = 0.022).
At both these time points, the benefit of tirofiban was predominantly owing to a reduction
in nonfatal MI and the need for repeat angioplasty. At 30 d, however, the reduction in the
composite endpoint from 12.2% in the placebo group to 10.3% in the tirofiban group no
longer reached statistical significance (Fig. 6). Similarly, 6-mo follow-up also failed to show
a statistically significant decrease in the composite endpoint in the tirofiban group, with
events occurring in 27.1% of placebo patients and 24.1% of tirofiban patients (p = 0.11).
To investigate the effects of tirofiban on the incidence of restenosis, 619 patients were
enrolled in a 6-mo angiographic substudy (30). Paired serial angiograms were available in
67% of these patients. Target lesion restenosis was defined as either (1) ≥50% stenosis in
those patients who had a <50% stenosis following the initial intervention; (2) late loss
in minimal lumen diameter (MLD) of ≥0.72 mm; or (3) late loss ≥50% of the initial gain
in MLD. Despite the multitude of definitions for restenosis, the results failed to show a sta-
tistically significant difference between the tirofiban and placebo groups. Cumulative dis-
tribution curves of MLD before and after PCI and at 6 mo were practically superimposable
(Fig. 7).
A
NALYSIS
The results of the RESTORE trial confirm that tirofiban is effective in reducing the inci-
dence of acute ischemic complications during PTCA/DCA in patients presenting with an
acute coronary syndrome, with extension of these benefits at least into the first week fol-
lowing the intervention. By 30 d, however, the magnitude of the benefit is substantially
Fig. 6. Kaplan-Meier curves of time to composite endpoint in the RESTORE trial. (Adapted from
ref. 28, with permission.)
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154 Part II / GPIIb/IIIa Blockade During Coronary Intervention
attenuated and no longer statistically significant. Furthermore, treatment with tirofiban
does not appear to lower the incidence of restenosis. These results are in contradistinction
to those of three contemporary abciximab trials (19,20,31) that suggested long-term bene-
fits with abciximab in similar patients. These trials however, included only urgent repeat
revascularization as a component of the composite endpoint, whereas the RESTORE trial
included any target vessel revascularization in the composite endpoint. In an attempt to
account for this difference and allow for comparison of the results between these different
trials, the RESTORE investigators performed a post hoc, blinded readjudication of the
30-d event rates by including only urgent revascularization (CABG or PCI) in the compos-
ite endpoint (Fig. 8). Utilizing this approach, a statistically significant decrease in the
30-d event rate from 10.5% in the placebo arm to 8.0% in the tirofiban arm was observed
(RRR = 24%, p = 0.052), matching the 8.3% event rate noted in the abciximab arm of the
EPIC trial (31).
RESTORE also differed from EPIC and EPILOG in the rate of nonfatal myocardial
infarction, reflecting differences in the frequency of serum CK measurements in these
trials. In RESTORE, a CK sample was obtained only at the end of the 36-h infusion, whereas
in EPIC and EPILOG, CK samples were obtained at multiple time points throughout the
first 48 h. Consequently, the nonfatal MI rate in the placebo group of RESTORE was only
5.7%, compared with 8.6 and 8.7% in EPIC and EPILOG, respectively. The lower MI rate
in the RESTORE placebo group translated to a smaller absolute risk reduction, even though
the absolute MI rates observed in the treatment arms of these trials were similar.
Other important differences between these trials, both in study design and in differing
practice patterns present at the time of the respective trials, have prohibited definitive com-
parisons between the various GPIIb/IIIa inhibitors. For example, in EPIC, drug adminis-
tration occurred before guidewire placement, as opposed to after guidewire placement,
Fig. 7. Cumulative distribution curves of minimum lumen diameter (MLD) before and after interven-
tion and at 6-mo follow-up in patients treated with tirofiban (■) or placebo (●) in the RESTORE
trial. (Adapted from ref. 30, with permission.)
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Chapter 7 / Tirofiban: The RESTORE and TARGET Trials 155
as was the case in RESTORE. Stent usage also differed among these trials. The use of
stents for abrupt vessel closure was greater in RESTORE (2.5%) than EPIC (0.6%). As a
result, there was a corresponding decrease in the frequency of CABG, from 3.6% in EPIC
to 1.3% in RESTORE. In light of these differences and the differing pharmacokinetic and
pharmacodynamic properties between tirofiban and abciximab, the TARGET trial was
designed to compare these two agents directly.
TARGET
STUDY DESIGN
The Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial was a double-
blind, double-dummy, multinational study conducted to test whether tirofiban was not
inferior to abciximab in patients scheduled to undergo coronary stenting. Eligible patients
included those undergoing either an elective or urgent procedure but not those in cardio-
genic shock or with ECG evidence of an acute ST-segment elevation myocardial infarc-
tion. Patients were randomized to receive either tirofiban (10 µg/kg bolus followed by a
0.15 µg/kg/min infusion for 18–24 h) with abciximab placebo or abciximab (0.25 mg/kg
bolus followed by a 0.125 µg/kg/min infusion for 12 h) with tirofiban placebo. Randomi-
zation was stratified by the presence or absence of diabetes; all patients received 250–
500 mg of aspirin and, when possible, a loading dose of 300 mg of clopidogrel. Heparin
was administered at the start of the procedure using a weight-based dosing nomogram
to achieve an ACT of 250 s.
The primary endpoint was a composite of death, nonfatal MI, or urgent target vessel
revascularization within 30 d of the procedure. A new myocardial infarction was defined
biochemically as a CK-MB level > 3× ULN in two successive blood samples, or electro-
cardiographically by the presence of new pathologic Q waves in two or more contiguous
Fig. 8. Time to composite endpoint 30-d event rates readjudicated to include only urgent or emergent
revascularizations. (Adapted from ref. 28, with permission.)
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156 Part II / GPIIb/IIIa Blockade During Coronary Intervention
leads. Serum chemistry samples were obtained at baseline and every 6 h for 24 h. For
patients with a non-ST-elevation MI who were enrolled in the study, the CK-MB value also
had to be 50% greater than the last preprocedural level for an event to qualify as an MI. Pre-
specified secondary endpoints included the occurrence of a primary endpoint in specific
subgroups: diabetics, females, patients >65 yr of age, patients pretreated with clopidogrel,
and patients enrolled in participating U.S. sites.
R
ESULTS
A total of 5308 patients were enrolled in the trial; 4809 of these patients actually received
study drug (2398 in the tirofiban group and 2411 in the abciximab group) and were included
in the analysis. Approximately 75% in each group were men, and 23% in each group were
diabetics. Most patients (63%) were enrolled with a diagnosis of an acute coronary syn-
drome, and almost all (95%) patients in both groups received a coronary stent. A native
coronary artery was the target vessel in 95% of cases. Restenotic lesions were treated in
5% of cases in each group. Most patients (81%) were treated in the United States.
The primary endpoint occurred in 7.6% of patients in the tirofiban group compared to
6.0% in the abciximab group. To meet prespecified criteria for noninferiority, the upper
bound of the 95% confidence interval (CI) of the hazard ratio (HR) had to be <1.47. In
fact, the upper bound of the one-sided 95% CI was 1.51, failing to meet the criteria neces-
sary to confirm the noninferiority of tirofiban to abciximab. Once the noninferiority of
tirofiban could not be established, the researchers were then able to assess whether abcixi-
mab was superior to tirofiban. The HR comparing tirofiban with abciximab showed a
statistically significant difference at 1.26 (95% CI = 1.01–1.57, p = 0.038) (Fig. 9). Most
of the benefit was derived from the difference in the nonfatal MI rates between the two
drugs (6.9% vs 5.4%, p = 0.04) (Fig. 10). Stratification of the MI rates by the magnitude
of the CK-MB level showed that the protective effect of abciximab was more prominent
with larger infarctions. For example, whereas the risk ratio comparing tirofiban with abcixi-
mab was 0.86 (p = NS) for CK-MB elevations of 3–5× ULN, at CK-MB levels of >10×
ULN, it increased to 1.47 (p = NS). Furthermore, the risk ratio for the development of
new abnormal Q waves was 1.66 (p = NS). Although underpowered to detect statistically
significant differences, these results suggest that the main benefit of abciximab over
Fig. 9. Incidence of primary endpoint at 30 d in the TARGET trial. (Adapted from ref. 29 with permission.)
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Chapter 7 / Tirofiban: The RESTORE and TARGET Trials 157
tirofiban may well be in the prevention of Q-wave or sizable non-Q-wave MIs. The ben-
efit of abciximab was obtained without any increase in risk of major bleeding, which was
<1.0% in both groups. There was, however, a significantly higher incidence of minor bleed-
ing attributable to abciximab (4.3% vs 2.8%, p < 0.001). There also was a significantly
greater incidence of thrombocytopenia in the abciximab group, although this did not
result in a higher incidence of either red cell or platelet transfusions.
Prespecified subgroup analyses revealed that patients who received a stent for the treat-
ment of an acute coronary syndrome obtained greater benefit from abciximab than those
patients who received a stent for other reasons. Patients <65 yr of age obtained greater
benefit with abciximab than with tirofiban, whereas both agents were equally effective
in patients >65 yr of age. The presence of diabetes did not result in any difference in effi-
cacy between the two agents. Stratification of outcome by treatment center revealed a
significant benefit of abciximab over tirofiban in patients treated at non-US centers, with
an event rate of 2.9% with abciximab and 6.9% with tirofiban. In fact, in the 3910 patients
treated at US centers, the HR was only 1.14, with the lower boundary of the 95% CI fall-
ing below unity. The most likely explanation for this difference can be found in the unex-
pectedly low event rate (2.9%) in the abciximab group of non-US patients. In EPISTENT
(32), for comparison, the 30-d composite endpoint of death, MI, or urgent target vessel
revascularization occurred in 5.3% of patients randomized to receive a stent and abciximab.
Furthermore, most patients enrolled in EPISTENT did not have an acute coronary syn-
drome and thus would be expected to have a lower event rate than those in TARGET, in
which 63% of patients were enrolled with a diagnosis of an acute coronary syndrome.
At 6 mo the difference between the two agents in the composite endpoint (14.4 vs 13.8,
p = NS) was attenuated and, although still favoring abciximab, was no longer statistically
significant (33). Once again, it was the nonfatal-MI event rates that predominantly influ-
enced the composite endpoint. A small decrease in the absolute risk reduction from 1.5%
at 30 d to 1.4% at 6 mo was sufficient to prevent the composite endpoint from reaching
statistical significance. Target vessel revascularization also failed to show a statistically
significant difference, not only at 30 d but, more importantly, also at 6 mo, confirming
that the nonspecificity of abciximab for the GPIIb/IIIa integrin does not affect the clinical
restenosis rate.
F
ig. 10. Hazard ratios for individual endpoints in the TARGET trial. (Adapted from ref. 29, with
permission.)
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158 Part II / GPIIb/IIIa Blockade During Coronary Intervention
ANALYSIS
The TARGET trial is the only trial to date that has directly compared two different
GPIIb/IIIa inhibitors. Based on the results of this trial, several conclusions can be drawn
that can help guide clinical practice. It is safe to say that in patients <65 yr of age and
particularly in those presenting with an acute coronary syndrome and who have a culprit
lesion that is amenable to PCI with stenting, abciximab is the preferred agent. Not only
is it associated with an improved clinical outcome, but it also provides this benefit with-
out an increase in clinically significant bleeding. Vigilance must be exercised, however,
since abciximab is more likely than tirofiban to cause a profound thrombocytopenia
(<20,000/mm
3
). One recent study cited an incidence of profound thrombocytopenia of
approx 0.5% (34), which correlates well with the 0.3% incidence observed in the TARGET
trial. Consequently, early (e.g., 4 h post bolus) and sequential complete blood counts should
be performed in all patients treated with abciximab.
The TARGET trial failed to show any difference between the two agents in elderly patients
(>65 yr) or those with chronic stable angina who are referred for elective PCI. Multivari-
ate modeling is necessary to understand these subgroup comparisons fully and to identify
patients who might derive equal benefit from both agents. The data do not support the theory
that the nonplatelet effects of abciximab influence the clinical restenosis rate. More signifi-
cant, and most likely reflecting the evolutionary improvements in the procedural aspects
of PCI in general, was the observation that the clinical restenosis rate, reflected by the
6-mo target vessel revascularization rate, was only approx 8% in both treatment arms (33).
It must be kept in mind that the main benefit of abciximab is in lowering the incidence
of periprocedural myocardial infarctions, as manifested by an asymptomatic elevation
in the CK-MB. Although the protective effect of abciximab is greater with larger infarc-
tions, in absolute numbers most of the periprocedural myocardial enzyme elevations are
of small magnitude, and their clinical significance remains a subject of significant debate
(35). The lack of a significant mortality difference at 6-mo and 1 yr (33a) follow-up sug-
gests that the increase in the periprocedural MI event rate is not associated with an increase
in cardiac death. Longer follow-up will be required to determine whether these infarctions
result in progressive LV dysfunction or late sudden cardiac death.
Several theories have been advanced to explain the superiority of abciximab over tiro-
fiban that was observed in the TARGET trial (29). Preferential blockade of the vitronectin
and Mac-1 receptors by abciximab leads to inhibition of platelet-endothelial cell, platelet-
smooth muscle cell, and monocyte-platelet aggregates and, as a result, interferes with the
recruitment of inflammatory cells to sites of vessel injury (36). It is plausible that attenu-
ation of this inflammatory response may help stabilize a ruptured plaque or dampen the
magnitude of the periprocedural platelet activation that has been shown to predict the risk
of acute ischemic events after PCI (37). Though GUSTO-IV (38) failed to show any bene-
fit of abciximab as adjunctive therapy in the medical treatment of patients with unstable
angina or non-ST-elevation myocardial infarction, differences in the timing of the event
or mechanical plaque disruption may explain abciximab’s demonstrated benefit in PCI.
Dosing Considerations
An alternative explanation for the observed differences between abciximab and tiro-
fiban is that the dose of tirofiban used was suboptimal and did not provide an equivalent
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Chapter 7 / Tirofiban: The RESTORE and TARGET Trials 159
degree of platelet inhibition to that provided by abciximab. In a pharmacodynamic dose-
escalation trial of abciximab (39) that served as the basis for the dose used in the EPIC
trial, a threshold of >80% inhibition of platelet aggregation to 20 µM ADP was selected
as the target for pharmacological efficacy. This degree of platelet inhibition correlated
to >80% receptor occupancy which, in animal models of coronary stenosis, has been shown
to prevent platelet thrombosis during coronary angioplasty (40). Consequently, studies
with the small-molecule agents adopted this threshold as the minimum degree of platelet
inhibition required to ensure efficacious dosing. However, in the only dose-ranging study
of tirofiban in patients undergoing PCI (26), the concentration of ADP used as agonist for
the light aggregometry assays was only 5 µM as opposed to the 20 µM ADP used in the phar-
macodynamic study for abciximab described above. So, despite the fact that the dose of
tirofiban that was eventually used both in the RESTORE and TARGET trials, was shown
to provide >90% inhibition of platelet activation, it remains uncertain that the degree of
platelet inhibition between the two agents in the TARGET trial was truly equivalent given
this difference in the potency of the agonist. In fact, in a study that did use 20 µM ADP
as the agonist, 30 patients with unstable angina were randomly assigned to receive either
standard-dose abciximab, PURSUIT-dose eptifibatide (41), or PRISM-PLUS-dose tiro-
fiban (42). The IPA was then assessed in PPACK-anticoagulated blood at baseline, at 10
and 40 min after the bolus, and at 4–6, 12, and 18–20 h. The median IPA was found to exceed
80% at all time points for abciximab and eptifibatide, whereas with tirofiban, only at the
18-h sample was the median IPA > 80% (43). Unfortunately, the generalizability of these
results to other acute coronary syndrome patients undergoing PCI is limited by the differ-
ence in the dose of tirofiban used in this study (acute coronary syndrome dose) and that
used in the TARGET trial (PCI dose).
In another comparative trial investigating the extent of platelet inhibition produced by
the three agents, Simon et al. (44) used a hybrid dose of tirofiban [RESTORE bolus (10 µg/
kg) + PRISM-PLUS infusion (0.10 µg/kg/min)] and measured 20 µM ADP-induced plate-
let aggregation at 10 min following the bolus. Once again, tirofiban exhibited a signifi-
cantly lower degree of platelet inhibition than did either abciximab or eptifibatide. Given
the timing of the blood sample, the suggestion is that the bolus dose of tirofiban may be
inadequate. Several limitations of the study, including differences in the patients’ baseline
characteristics, differences in dosing regimens, and the lack of information regarding
the use of clopidogrel preclude definitive conclusions (45).
In an attempt to investigate further the issue of inadequate dosing of tirofiban, especi-
ally since patients with an acute coronary syndrome have been shown to exhibit a greater
degree of platelet activation (46) than in patients without, we (47) randomly assigned 20
acute coronary syndrome patients who were undergoing planned coronary stenting to tiro-
fiban (10 µg/kg bolus, 0.15 µg/kg/min × 18 h) or abciximab (0.25 mg/kg bolus, 0.125 µg/
kg/min × 12 h) and measured the IPA to 20 µM ADP at baseline, 5, 15, 30, 45, and 60 min
after drug administration. All patients were pretreated with ASA (325 mg) and clopidogrel
(300 mg) and received heparin to maintain an ACT of at least 250 s. At all time points, the
IPA with tirofiban was less than that with abciximab (Fig. 11). This difference was sta-
tistically significant only at the 15-min time interval, consistent with the suggestion that the
bolus dose of tirofiban may be suboptimal. Furthermore, the mean time to balloon infla-
tion (13 ± 2 min) coincided with the timing of the maximal difference in the IPA between
the two drugs, suggesting that at the crucial moment of initial balloon inflation, tirofiban
less effectively inhibits platelet activation than does abciximab.
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