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170 Part II / GPIIb/IIIa Blockade During Coronary Intervention
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 171
Fig. 1. Protocol outlines for the 11 large-scale trials of glycoprotein (GP)IIb/IIIa blockade in interventional cardiology. (A) Trials during elective or
urgent PCI. (B) Trials during refractory unstable angina or acute myocardial infarction. ACT, activated clotting time; AVC, abrupt vessel closure; DCA,
directional coronary atherectomy; IABP, intraaoric balloon pump; LD Hep, low-dose, weight-adjusted heparin; MI, myocardial infarction; PTCA,
balloon angioplasty; SD Hep, standard-dose, weight-adjusted heparin; 135/0.5, 135/0.75, and 180/2.0/180 = eptifibatide doses (see text); pts, patients.
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172 Part II / GPIIb/IIIa Blockade During Coronary Intervention
Table 1
Randomized Interventional Trials: Patient Populations
Agent No. of Enrollment
Trial tested patients period Entry criteria
EPIC Abciximab 2099 11/91–11/92 High-risk PTCA or DCA
Acute MI—within 12 h (direct or rescue PTCA)
Recent MI—within prior 7 d
Unstable angina—within 24 h of chest pain (rest or postinfarction
angina with ischemic ECG changes)
Clinical-morphologic criteria (ACC/AHA lesion score B2 or C,
ACC/AHA score B1 with DM or with women age > 65 yr)
EPILOG Abciximab 2792 2/95––12/95 Urgent or elective PTCA, DCA, TEC, or laser
Excluding unstable angina or acute MI (EPIC criteria) within
prior 24 h, elective stents, rotational atherectomy
EPISTENT Abciximab 2399 7/96–9/97 Coronary intervention suitable for PTCA or elective stent
Excluding acute MI within 24 h, rotational atherectomy
IMPACT II Eptifibatide 4010 11/93–11/94 All clinical indications, all approved interventions
ESPRIT Eptifibatide 2064 6/99–2/00 Elective stent for which GPIIb/IIIa inhibitor would not be routinely used
Excluding acute MI within 24 h or unstable ischemia with ongoing chest
pain or prior thienopyridine use
RESTORE Tirofiban 2139 1/95–12/95 High-risk PTCA or DCA
Acute MI—within 72 h (Q-wave or non-Q-wave)
Unstable angina—within 72 h (chest pain at rest or on minimal effort with
ECG changes, hemodynamic changes, or angiographic thrombus)
CAPTURE Abciximab 1265 5/93–12/95 Refractory unstable angina
Unstable angina—within 48 h (chest pain with ECG changes) despite
iv heparin and nitroglycerin
RAPPORT Abciximab 483 11/95–2/97 Primary PTCA for acute ST elevation MI—within 12 h
ISAR-2 Abciximab 401 N/A Primary stent for acute ST elevation MI—within 48 h
ADMIRAL Abciximab 300 7/97–12/98 Primary PCI for acute ST elevation MI—within 12 h
CADILLAC Abciximab 2681 11/97–9/99 Primary PCI for acute ST elevation MI—within 12 h
TARGET Abciximab vs 4809 12/99–8/00 Coronary intervention suitable for stent
tirofiban Excluding acute MI or cardiogenic shock
Abbreviations: ACC/AHA, American College of Cardiology/American Heart Association modified lesion complexity score (61); DCA, directional coronary
atherectomy; DM, diabetes mellitus; ECG, electrocardiographic; MI, myocardial infarction; N/A, not available; PCI, percutaneous coronary intervention (balloon
angioplasty, stent, or other device); PTCA, coronary balloon angioplasty; TEC, transluminal extraction catheter atherectomy.
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 173
Table 2
Randomized Interventional Trials: Heparin Regimens and Vascular Sheath Removal
Sheath removal
b
Heparin (time after
Trial Bolus
a
target ACT
a
(s) Postprocedural infusion
b
interventional procedure)
EPIC 10–12,000 U initial 300–350 s >12 h >6 h after 12-h study drug
3000 U additional to Target aPTT 1.5–2.5 × control infusion (>18 h total)
maximum total 20,000 U
EPILOG “Standard-dose”: 100 U/kg “Standard-dose” > 300 s None When ACT < 175 s
“Low-dose”: 70 U/kg “Low-dose” > 200 s None (approx 2–6 h)
EPISTENT Placebo: 100 U/kg Placebo > 300 s
Abciximab: 70 U/kg Abciximab > 200 s None When ACT < 175 s
(approx 2–6 h)
IMPACT II 100 U/kg 300–350 s None When aPTT < 45 s
(4–6 h)
ESPRIT 60 U/kg 200–300 s None 3–4 postprocedure
RESTORE 10,000 U 300–400 s None When ACT < 180 s
150 U/kg for weight < 70 kg
CAPTURE 10,000 U >300 s 1 h after PTCA 4–6 h
(all patients received infusion (>24–30 h total, including
for 24 h before PTCA: during preprocedural
target aPTT 2.0–2.5 × control) study drug infusion)
RAPPORT 100 U/kg >300 s None When ACT < 175 s
(4–6 h)
ISAR-2 (5000 U before catheterization) None Control: 1000 U/h for 12 h N/A
Control: 10,000 U after sheath
Abciximab: 2500 U Abciximab: none
ADMIRAL 70 U/kg >200 s 7 U/kg/h for 24 h 4–6 h after heparin
infusion stopped
CADILLAC (5000 U before catheterization) Control > 350 s None N/A
by nomogram Abciximab 200–300 s
TARGET 70 U/kg >250 s None When ACT < 175 s
(approx 2–6 h)
Abbreviations: ACT, activated clotting time; N/A, information not available; aPTT, activated partial thromboplastin time.
a
Prior to first balloon inflation or device activation of interventional procedure.
b
Recommended by protocol.
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174 Part II / GPIIb/IIIa Blockade During Coronary Intervention
THE EPISTENT TRIAL
EPISTENT is described in detail in Chapter 5. Previous trials of GPIIb/IIIa receptor
blockade during PCI had excluded patients undergoing elective stent implantation, because
of rapid changes in the “optimal stenting” technique during the time periods that these
trials were under way as well as uncertainties regarding the best conjunctive anticoagu-
lation regimen. EPISTENT was therefore designed to evaluate the complementary and
comparative roles of GPIIb/IIIa blockade with abciximab and stenting. A total of 2399
patients undergoing urgent or elective percutaneous revascularization of lesions suitable
for balloon angioplasty (PTCA) or stenting were enrolled between 1996 and 1997 and
randomized to stent plus placebo, stent plus abciximab (bolus and 12-h infusion), or
PTCA plus abciximab (14). “Bailout” or unplanned stents were utilized in only 19% of
patients in the PTCA group. The primary efficacy endpoint of death, myocardial infarc-
tion, or urgent revascularization was assessed at 30 d, with clinical follow-up to 6 mo and
1 yr. Additionally, an angiographic substudy of 900 patients (300 in each treatment group)
was carried out to evaluate the influence of abciximab on restenosis.
T
HE IMPACT II TRIAL
IMPACT II is described in detail in Chapter 6. This “all comers” trial tested the clinical
efficacy of eptifibatide among 4010 patients undergoing percutaneous intervention for
any clinical indication between 1993 to 1994 (15). Patients received aspirin and weight-
adjusted heparin and were randomized to placebo, eptifibatide 135 µg/kg bolus followed
by an infusion of 0.5 µg/kg/min for 20–24 h (“135/0.5 group”), or eptifibatide 135 µg/kg
bolus followed by an infusion of 0.75 µg/kg/min for 20–24 h (“135/0.75 group”). Clinical
outcome was assessed at 30 d and 6 mo. An angiographic substudy, enrolling approx 900
patients, was performed to assess the influence of eptifibatide on angiographic restenosis.
T
HE ESPRIT TRIAL
The ESPRIT trial is described in Chapter 6. The disappointing treatment effect of epti-
fibatide observed in the IMPACT-II trial (see the 30-Day Efficacy section) was thought
to be at least partly caused by the dose employed, which was subsequently observed to
result in blockade of only 30–50% of GPIIb/IIIa receptors (16). Further dosing studies (17)
and pharmacodynamic modeling demonstrated that a double bolus of 180 µg/kg given
10 min apart with a 2.0 µg/kg/min infusion of eptifibatide uniformly produced and
maintained >80% blockade of GPIIb/IIIa receptors. This high-dose eptifibatide regimen
was tested among patients in the setting of coronary stenting in the ESPRIT trial. Because
of ethical concerns regarding randomization of patients to placebo during 1999–2000, a
time when the efficacy of GPIIb/IIIa blockade had already been well documented, patients
were eligible for inclusion in ESPRIT only if they “...in the opinion of the treating phy-
sician would not routinely be treated with a glycoprotein IIb/IIIa inhibitor during PCI...”
(18). Patients within 24 h of acute myocardial infarction or with unstable myocardial
ischemia and “continuing chest pain precipitating urgent PCI” were excluded, as were those
who were pretreated with a thienopyridine platelet inhibitor (ticlopidine or clopidogrel).
The patients were randomized in a double-blind fashion to receive either placebo or
eptifibatide immediately prior to stent implantation, with infusions for 18–24 h; heparin
doses in both the placebo and eptifibatide arms were reduced, with 60 U/kg bolus and tar-
get ACT >250 s. The planned sample size was 2400 patients, but the trial was terminated
on the basis of an interim review demonstrating efficacy after 2064 patients had been
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 175
enrolled. The primary endpoint was the composite of death, myocardial infarction, urgent
target vessel revascularization, or bailout GPIIb/IIIa inhibitor therapy within 48 h, with
follow-up to 30 d, 6 mo, and 1 yr.
T
HE RESTORE TRIAL
RESTORE is described in detail in Chapter 7. The clinical efficacy of tirofiban was
tested during 1995 among a total of 2139 patients considered to be at high risk for coro-
nary balloon angioplasty owing to unstable angina or myocardial infarction (19). Patients
were randomized after passage of a guidewire across a target lesion to placebo or tirofiban,
administered as a 10 µg/kg bolus followed by a 0.15 µg/kg/min infusion for 36 h. The
predefined primary endpoint of the study was the occurrence of death, myocardial infarc-
tion, or any target vessel repeat revascularization by 30 d; clinical outcome was also assessed
at 6 mo. A post hoc reclassification of revascularization events was performed to produce
a composite endpoint comparable to that of other interventional trials by including only
urgent revascularization procedures. An angiographic substudy of approx 600 patients
(300 in each group) evaluated the effect of tirofiban on restenosis.
T
HE CAPTURE TRIAL
CAPTURE is described in detail in Chapter 9. This trial differed from the other inter-
ventional GPIIb/IIIa trials in that CAPTURE evaluated a strategy of pretreatment with
abciximab prior to balloon angioplasty among patients with refractory unstable angina.
Patients qualified for enrollment if they had unstable angina with episodes of chest pain
and ischemic electrocardiographic changes, despite therapy with intravenous heparin
and nitroglycerin, and had been demonstrated on angiography to have a lesion suitable
for coronary angioplasty (20). All patients received aspirin and were randomized to
placebo or abciximab for 18–24 h prior to angioplasty and continued for 1 h after comple-
tion of the procedure. Heparin was administered and vascular sheaths remained in place
from enrollment throughout the pretreatment phase and until at least 1 h after angioplasty.
Planned sample size was 1400 patients, but the trial was stopped on the basis of efficacy
at the third interim analysis with 1265 patients enrolled between 1993 and 1995. The pri-
mary endpoint of death, myocardial infarction, or urgent revascularization was assessed
at 30 d, with continued clinical follow-up through 6 mo.
T
HE RAPPORT TRIAL
RAPPORT is described in detail in Chapter 12. A total of 483 patients treated by pri-
mary balloon angioplasty within 12 h of symptoms of acute myocardial infarction were ran-
domized to receive placebo or abciximab (bolus and 12 h infusion) in addition to aspirin
and heparin (21). The primary endpoint was death, recurrent myocardial infarction, or
any (elective or urgent) repeat target vessel revascularization by 6 mo. A composite end-
point of the acute ischemic events of death, reinfarction, or urgent repeat target vessel
revascularization (comparable to the primary endpoints used in the other trials) was also
assessed at 7 d, 30 d, and 6 mo.
T
HE ISAR-2 TRIAL
ISAR-2 is described in detail in Chapter 12. This was a nonblinded study intended
primarily to assess the impact of abciximab on restenosis following primary PCI for acute
myocardial infarction. A total of 401 patients were randomized to either “conventional
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176 Part II / GPIIb/IIIa Blockade During Coronary Intervention
care” or adjunctive abciximab (bolus plus infusion) during stent implantation performed
within 48 h of onset of chest pain (22). Heparin doses were reduced in the abciximab arm.
The primary endpoint was late loss of angiographic luminal dimensions by 6-mo follow-
up; clinical events (death, myocardial reinfarction, or target vessel revascularization)
were assessed at 30 d and 6 mo.
T
HE ADMIRAL TRIAL
ADMIRAL is described in Chapter 12. This trial was designed to determine the influ-
ence of abciximab therapy among a broad unselected population of patients with acute
myocardial infarction in the context of a management strategy of primary stent implanta-
tion. Patients within 12 h of acute infarction in whom stenting was planned were enrolled
and randomized in a double-blind fashion to placebo or abciximab bolus plus infusion
(23). The initial heparin bolus was 70 U/kg in both arms. Of the 300 patients enrolled,
26% were randomized and administered study drug in the ambulance or emergency
department, with the remainder receiving study agent in the intensive care unit or cath-
eterization laboratory. Percutaneous coronary revascularization was attempted in 92–
95% of patients after angiography. The primary composite endpoint of death, myocardial
reinfarction, or urgent target vessel revascularization was assessed at 30 d and 6 mo.
T
HE CADILLAC TRIAL
CADILLAC is described in detail in Chapter 12. This large-scale trial assessed the
effectiveness of stenting and abciximab among 2082 patients undergoing primary PCI
within 12 h of acute myocardial infarction (24). Excluded from enrollment were those
with bypass graft stenoses, coronary lesions requiring multivessel intervention, or “pre-
specified anatomical conditions...that would reduce the likelihood of successful stenting.”
Using a 2-by-2 factorial design, patients were randomized to PTCA alone, PTCA plus
abciximab, stent alone, or stent plus abciximab. Heparin doses were adjusted by nomo-
gram to provide a lower ACT target range for patients receiving abciximab. The primary
endpoint was the composite of death, reinfarction, repeat target vessel revascularization,
or disabling stroke by 6 mo after randomization; clinical endpoints were also assessed at
30 d. An angiographic substudy of 900 patients was performed to determine the impact
of therapy on the risk of restenosis at 6 mo.
T
HE TARGET TRIAL
TARGET is described in Chapter 7. This is was the first (and to date only) comparative
trial of two different GPIIb/IIIa antagonists, performed to determine whether or not tiro-
fiban was inferior to abciximab during coronary stenting. As all patients received a GPIIb/
IIIa inhibitor, those undergoing urgent or elective procedures were eligible for enroll-
ment (25). Patients were randomized on a double-blind, double-dummy basis to receive
either abciximab 0.25 mg/kg bolus and 0.125 µg/kg/min (maximum 10 µg/min) infusion
for12-h or tirofiban 10 µg/kg bolus and 0.15 µg/kg/min infusion for 18–24 h. Pretreatment
with clopidogrel and aspirin was encouraged, and a reduced-dose, weight-adjusted hepa-
rin regimen (70 U/kg, target ACT > 250 s) was used in both arms. Of the total 5308 patients
enrolled, 4809 received study drug and formed the study population. The primary end-
point was the composite of death, myocardial infarction, or urgent target vessel revascu-
larization at 30 d, with clinical follow-up at 6 mo and 1 yr.
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 177
Intertrial Comparisons
Pooled analyses of these 12 large-scale trials of GPIIb/IIIa blockade allow general prin-
ciples regarding the efficacy and safety of this treatment strategy to be evaluated. Important
differences among the trials must be recognized, however, with regard to patient popu-
lations, study drug regimens, adjunctive medical therapies, and endpoint assessment.
E
NTRY CRITERIA
As a general rule, therapies that are effective will often exhibit the most clinical effi-
cacy among patients who are at heightened risk for the events to be prevented. For this
reason, initial trials of GPIIb/IIIa blockade during coronary intervention often focused
on patients deemed to be at high risk for periprocedural ischemic complications. The first
trial, EPIC, designated high-risk status by either the unequivocal unstable ischemic syn-
dromes or complex angiographic target lesion morphology in combination with clinical
criteria. The RESTORE entry criteria were even narrower than those of EPIC, including
only patients with unstable ischemic syndromes, the subgroup that had been found in EPIC
to have experienced the most clinical benefit from GPIIb/IIIa blockade (see below) (26).
CAPTURE was a trial focused on the particular application of GPIIb/IIIa blockade as
pretreatment among patients with refractory unstable angina, defined by ongoing ische-
mic symptoms and electrocardiographic changes despite optimal medical management.
RAPPORT, ISAR-2, ADMIRAL, and CADILLAC specifically evaluated patients under-
going primary angioplasty or stenting for ST elevation acute myocardial infarction.
In contrast, one of the primary objectives of the EPILOG trial was to assess whether
the clinical efficacy of abciximab therapy could be extended to the low- as well as high-
risk patients undergoing coronary intervention; all patients were therefore to be included,
except those with severe unstable angina (with symptoms and electrocardiographic changes
within the previous 24 h) for whom the profound benefit of abciximab had already been
demonstrated in EPIC (26), or those with acute myocardial infarction, a setting under
evaluation in dedicated trials. Similarly, the philosophy behind design of IMPACT-II was
one of broad applicability, and patients representing various risk profiles were enrolled.
More recently, the EPISTENT and ESPRIT trials sought to evaluate the role of GPIIb/IIIa
blockade with abciximab and eptifibatide, respectively, during the current interventional
era of widespread stenting with adjunctive thienopyridine therapy.
S
TUDY DRUG REGIMENS
Aside from CAPTURE, all trials evaluated a strategy whereby study drug (GPIIb/IIIa
inhibitor or placebo) was administered as a bolus immediately prior to coronary interven-
tion, followed by infusions of varying durations. The EPIC trial was the only study to test
a bolus-only regimen of a GPIIb/IIIa antagonist. Given that abciximab has the longest
duration of GPIIb/IIIa blockade of all the agents under evaluation, and that the group in
EPIC receiving the bolus of abciximab experienced only a small and statistically insignif-
icant reduction in endpoints compared with placebo (see below), it was concluded that post-
bolus infusions would be required with all these compounds in subsequent trials for optimal
passivation of the arterial plaque and reduction in clinical ischemic events. The durations
of study drug infusion were based on pharmacodynamic differences among the agents:
24-h or 36-h infusions of eptifibatide and tirofiban were chosen for the IMPACT-II and
RESTORE trials, respectively, given the rapidly reversible pharmacodynamics of these
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178 Part II / GPIIb/IIIa Blockade During Coronary Intervention
drugs, compared with the 12-h infusion of abciximab. With the greater postprocedural
stability imparted by stenting compared with balloon angioplasty (particularly with thieno-
pyridine therapy), the more contemporary trials of eptifibatide (ESPRIT) and tirofiban
(TARGET) used infusions of only 18–24 h (or less) to enhance compatibility with shortened
hospital length-of-stays.
As previously described, CAPTURE utilized a 24-h pretreatment regimen of study
drug. Abciximab was administered for only 1 h after the interventional procedure, partly
because this trial was designed and initiated before the findings of EPIC regarding the
importance of a postprocedural abciximab infusion were fully appreciated. The short post-
procedural drug infusion may have adversely influenced the magnitude of treatment effect
observed in the CAPTURE trial.
C
ONJUNCTIVE HEPARIN AND VASCULAR ACCESS SITE MANAGEMENT
Protocol guidelines for conjunctive heparin dosing and vascular sheath removal are
summarized in Table 2. As described below, a major limitation of abciximab therapy in
EPIC was a marked increase in the incidence of bleeding complications. This hemorrhagic
risk appeared to be linked to excessive intraprocedural heparin dosing as well as the prac-
tice of leaving vascular access sheaths in place with ongoing heparin infusion for the entire
12-h study drug infusion period. A pilot study demonstrated that vascular sheaths could
be removed and hemostasis achieved during abciximab infusion, if heparin had been dis-
continued, and that bleeding rates actually tended to be less with this strategy than with
prolonged sheath dwell times (12). Moreover, the risk of hemorrhagic complications was
further diminished by reduction and weight adjustment of the procedural heparin doses.
Based on these findings, the EPILOG trial explicitly tested low-dose vs standard-dose
weight-adjusted heparin regimens with abciximab, and the other trials incorporated some
form of protocol-directed limitation or weight adjustment of heparin dosing. Trials per-
formed after EPIC recommended that little or no heparin infusion be administered after
the procedure and that vascular access sheaths be removed early (usually during study drug
infusion). Notably, however, postprocedural heparin infusions were often used during
the trials of primary PCI for acute myocardial infarction; in RAPPORT, for example,
median dwell times for vascular access sheaths were 17–19 h. Similarly, vascular sheaths
remained in place with ongoing heparin infusion for the entire 24-h pretreatment period
between qualifying angiography and percutaneous revascularization in CAPTURE.
O
THER MEDICATIONS
All patients in these interventional trials of intravenous GPIIb/IIIa blockade were treated
with aspirin before the procedure and indefinitely thereafter. Although it is unlikely that
aspirin adds significant platelet antiaggregatory effect during ongoing administration of
a GPIIb/IIIa antagonist, there may well be an incremental benefit of its inhibition of plate-
let activation or antiinflammatory properties. Moreover, long-term ischemic event rates
are suppressed by chronic aspirin therapy but would not be expected to be influenced by
a brief periprocedural administration of a GPIIb/IIIa agent. Other anticoagulant drugs
were generally restricted by protocol to the extent that they could exacerbate bleeding com-
plications of the study agent. Patients on therapeutic warfarin therapy were excluded, as
were those in whom administration of dextran was planned. Thrombolytic therapy as an
adjunct to angioplasty was discouraged, with reduced doses suggested if administration
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 179
of these drugs was considered imperative. Antianginal and other medical therapies were
not protocol-directed and were utilized at the discretion of physicians at the clinical sites.
The protocol-specified use of thienopyridines in these trials varied in parallel with the
evolution of enhanced antiplatelet regimens for coronary stenting. Trials performed early
in the stent era specified that ticlopidine or clopidogrel be administered for 4 wk after
stenting. Data derived from EPISTENT as well as other studies, however, suggested that
periprocedural ischemic events were reduced by pretreatment with thienopyridines (27).
As a result, the TARGET trial strongly encouraged administration of a loading dose of
clopidogrel (300 mg) 2–6 h prior to PCI as “background” therapy to enhance the efficacy
of tirofiban relative to abciximab. Conversely, the exclusion of patients pretreated with
clopidogrel from enrollment in the ESPRIT trial could be seen as a means of enhancing
the apparent differences between placebo and eptifibatide.
T
RIAL CONDUCT AND ENDPOINTS
The interventional trials shared many common design and analysis features. Most trials
were blinded, with the exception of ISAR-2, CADILLAC, and the asymmetric balloon
angioplasty plus abciximab arm of EPISTENT. Endpoints were adjudicated by review
of primary data by independent, blinded Clinical Events Committees for all studies except
ISAR-2. Myocardial infarction was in general identified by new Q-waves or creatine kinase-
MB fraction (CK-MB) elevations ≥3 times the control value. Urgent repeat revascular-
ization was defined by evidence of precipitating myocardial ischemia and rapid (within
24 h) performance of the revascularization procedure. Bleeding events were classified as
“major” or “minor” based on observed hemorrhage and changes in hemoglobin accord-
ing to the criteria of the Thrombolysis in Myocardial Infarction (TIMI) Study Group (28).
Important differences existed, however, with regard to assessment of periprocedural
myocardial infarctions. In all but two of the trials, Clinical Events Committees reviewed
CK-MB enzyme values that had been obtained systematically by a protocol-driven sched-
ule (every 6–8 h for the first 24 h) and thereby identified myocardial infarctions that may
or may not have been noted by site investigators. In contrast, myocardial enzyme values
were not routinely obtained in the RESTORE or CADILLAC trials, but were instead drawn
only when ischemic events were suspected to have occurred; Clinical Events Committee
reviews were thus confined to adjudication of events that had been identified by the site
investigators. As a consequence, endpoint (re-)infarction rates in RESTORE and CADILLAC
were substantially lower than in the other trials discussed here, thereby substantially
reducing the ability of those trials to identify the therapeutic effect of GPIIb/IIIa blockade.
30-Day Efficacy
Event rates for the composite 30-d endpoint of death, myocardial infarction, or urgent
repeat revascularization in the various treatment groups of the 11 interventional trials
without active controls (i.e., excluding TARGET) are summarized in Fig. 2. Ischemic end-
point event rates were consistently diminished by GPIIb/IIIa blockade in all the trials,
although the magnitude of treatment effect was variable. In EPIC (11), this composite event
rate was reduced from 12.8% among patients receiving placebo to 11.4% among patients
randomized to the abciximab bolus (10% relative risk reduction, p = 0.43) and to 8.3%
among patients randomized to the abciximab bolus and 12-h infusion (35% relative risk
reduction, p = 0.008). The treatment effect of abciximab appeared to be amplified (up to
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