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180 Part II / GPIIb/IIIa Blockade During Coronary Intervention
a 56% risk reduction) in the subsequent EPILOG trial (13): the composite endpoint event
rate was 11.7% in the placebo group, 5.2% in the abciximab with low-dose heparin group
(56% relative risk reduction, p < 0.0001), and 5.4% in the abciximab with standard-dose
heparin group (54% relative reduction, p < 0.0001). A treatment effect of similar propor-
tion was observed among patients receiving abciximab compared with placebo in EPISTENT
(14); the primary efficacy composite endpoint occurred in 10.8% of patients in the stent
plus placebo arm, 6.9% of patients in the balloon plus abciximab arm (36% relative risk
reduction, p = 0.007), and 5.3% of patients in the stent plus abciximab arm (51% relative
risk reduction, p < 0.001).
In contrast, although the IMPACT-II trial provided evidence that eptifibatide dimin-
ished periprocedural ischemic events, the magnitude of treatment effect was less marked
than in the abciximab trials and did not quite reach statistical significance (15). The com-
posite endpoint in IMPACT-II occurred in 11.4% of patients in the placebo group, 9.2%
of patients in the eptifibatide 135/0.5 group (19% relative risk reduction, p = 0.063), and
Fig. 2. Composite 30-d endpoint (death, myocardial infarction, or urgent repeat revascularization)
event rates for the 11 GPIIb/IIIa interventional trials without active controls (i.e., TARGET excluded).
RESTORE trial endpoints listed here are for the published post hoc analysis including only urgent
repeat revascularization for consistency with the other trials. The reported composite endpoint at 30 d
in CADILLAC was death, myocardial reinfarction, urgent target vessel revascularization, or disabling
stroke. The reported composite endpoint at 30 d in RAPPORT, ISAR-2, and ADMIRAL was death,
myocardial reinfarction, or urgent target vessel revascularization. *EPISTENT trial groups compared
with reference group of Placebo + Stent; thus, the “placebo control” for the Abciximab + PTCA group
underwent stenting rather than PTCA. B, bolus; B+I, bolus plus infusion; LDH, low-dose, weight-
adjusted heparin; MI, myocardial infarction; PTCA, percutaneous transluminal coronary angioplasty;
SDH, standard-dose, weight-adjusted heparin; 135/0.5, 135/0.75, and 180/2.0/180 = eptifibatide doses
(see text).
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 181
9.9% of patients in the eptifibatide 135/0.75 group (16% relative risk reduction, p = 0.22).
No dose response was observed among the eptifibatide doses evaluated in this study.
Subsequent to IMPACT-II, it was observed that the binding of eptifibatide to the GPIIb/
IIIa receptor was exaggerated in blood anticoagulated by the calcium-chelating anticoag-
ulant citrate (which had been used in the GPIIb/IIIa dose-finding studies) relative to that
which would occur at physiologic calcium concentrations (16). A higher dose of eptifiba-
tide, with a double bolus to ensure adequate platelet receptor blockade during the early
period immediately after plaque injury, led to a substantially greater treatment effect in
the ESPRIT trial (18), in which the 30-d composite endpoint was reduced from 10.5 to
6.8% (35% risk reduction, p = 0.0034).
In the RESTORE trial (19), the efficacy of tirofiban during high-risk balloon angioplasty
was also less than had been anticipated based on the results of the EPIC trial. The prede-
fined primary endpoint of death, myocardial infarction, or repeat target lesion revascular-
ization in RESTORE occurred in 12.2% of patients in the placebo group and 10.3% of
patients in the tirofiban group (16% relative risk reduction, p = 0.16). With the post hoc reclas-
sification of revascularization events to allow comparison with the other trials, the 30-d
composite of death, myocardial infarction, or urgent revascularization was 10.5% in the
placebo group and 8.0% in the tirofiban group (24% relative risk reduction, p = 0.052).
In CAPTURE (20), a 24-h period of pretreatment with abciximab among patients with
refractory unstable angina prior to angioplasty reduced the primary composite endpoint from
15.9% in the placebo group to 11.3% in the abciximab group (29% relative risk reduction,
p = 0.012). Clinical benefit of abciximab began to accrue during the pretreatment phase
before the angioplasty procedure, with the preprocedural myocardial infarction rate reduced
from 2.1% among control patients to 0.6% among those treated with abciximab (p = 0.029).
Among patients undergoing primary PCI for acute myocardial infarction, the treat-
ment effect of abciximab was generally concordant with that observed in the elective PCI
trials. In RAPPORT (21), the composite endpoint of death, recurrent myocardial infarction,
or urgent target vessel revascularization at 30 d was significantly reduced by abciximab
from 11.2 to 5.8% (48% relative risk reduction, p = 0.038). Similarly, the 30-d composite
endpoint was reduced from 10.5 to 5.0% (52% relative risk reduction, p = 0.038) in ISAR-
2 (22) and from 14.6 to 6.0% (59% relative risk reduction, p = 0.01) in ADMIRAL (23).
Notably, among the subset of patients in ADMIRAL who had been randomized and received
their study drug before arriving in the catheterization laboratory, event rates were markedly
reduced, from 21.1 to 2.5%.
In contrast, the CADILLAC trial did not show a significant benefit of abciximab in
reducing 30-d complication rates among patients receiving stents (5.7% vs 4.4%, p = NS),
although there was a treatment effect of abciximab in patients treated with balloon angio-
plasty (8.3% vs 4.8%, p = 0.02) (24). Importantly, however, end-point event rates overall
in CADILLAC were much lower than in the other acute MI abciximab trials, particularly
for the endpoint of reinfarction (which was not systematically adjudicated), raising impor-
tant concerns regarding whether CADILLAC was appropriately designed to evaluate the
treatment effect of GPIIb/IIIa inhibition on acute ischemic complications. It was notable,
for example, that although subacute thrombosis rates were reduced by abciximab from
1.4 to 0.4% (p < 0.001), no differences in reinfarction rates were detected (0.9 vs 0.8%).
When directly compared with abciximab among patients undergoing stenting in the
TARGET trial (29), tirofiban was found to provide inferior protection from acute ischemic
events. The 30-d composite endpoint occurred in 7.6% of patients receiving tirofiban,
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182 Part II / GPIIb/IIIa Blockade During Coronary Intervention
compared with 6.0% of patients randomized to abciximab (hazard ratio for tirofiban 1.26,
95% confidence interval 1.01–1.57, p = 0.038). Differences in outcome between the two
agents emerged within 2 d of the PCI procedure.
C
OMPONENTS OF THE 30-DAY ENDPOINT
The breakdown of individual 30-d endpoints is detailed in Table 3. In general, the treat-
ment effect of GPIIb/IIIa blockade was similar for each of the components of the compos-
ite endpoints used in this trial. Point estimates of event rates for infrequent complications
such as death were imprecise, and although a trend toward diminished mortality was
observed in most of the studies, these differences did not reach statistical significance.
Myocardial infarction rates were consistently diminished by treatment with GPIIb/IIIa
inhibitors compared with placebo; rates of urgent repeat revascularization were usually
reduced as well. The EPISTENT trial requires particular explanation owing to the asym-
metry of the treatment groups (abciximab plus stent or abciximab plus PTCA compared
with the reference arm of placebo plus stent). Compared with stenting alone, adjunctive use
of abciximab with stenting reduced the rates of death, myocardial infarction, and repeat
revascularization. Compared with stenting alone, abciximab with balloon angioplasty was
associated with equivalent rates of death and revascularization but lower rates of myo-
cardial infarction.
The most frequent ischemic event prevented in these GPIIb/IIIa interventional trials
was myocardial infarction, predominantly non-Q-wave infarction. Although the clinical
importance of such periprocedural non-Q-wave infarctions following percutaneous coro-
nary revascularization was initially controversial, virtually every contemporary study that
has examined the impact of periprocedural enzyme release over an adequate follow-up
period has demonstrated that patients who experience myocardial infarction during or after
coronary intervention are at significantly greater risk for late cardiac death than those who
do not (30–36). Although an increased risk of late events has been observed in these studies
even among patients with “small” CK-MB elevations (>1–1.5 times control) (33–35), the
extent of mortality risk appears to be proportional to the degree of enzyme elevation. It
is therefore relevant that the effect of the GPIIb/IIIa inhibitors on reducing periprocedural
myocardial infarction in these trials was primarily observed for large non-Q-wave infarc-
tions (CK-MB >5 times control), confirming that the ischemic events prevented were clin-
ically relevant, not merely laboratory abnormalities.
E
FFICACY IN PATIENT SUBGROUPS
Although it might be anticipated that intense platelet inhibition with a GPIIb/IIIa inhib-
itor would provide substantial clinical benefit only among patients at high risk for throm-
botic complications, a consistent treatment effect has been observed among all subgroups
of patients enrolled in the trials. No clinical or angiographic (37) parameter has been found
to identify patients reliably who do not benefit from GPIIb/IIIa blockade. This finding was
most apparent in EPILOG and EPISTENT, as well as ESPRIT, in which the reduction in
acute 30-d ischemic endpoints was of similar magnitude among patients defined by ische-
mic syndrome or a number of demographic or clinical characteristics.
Long-Term Efficacy
Patients were followed for at least 6 mo after randomization in all the interventional
trials for assessment of clinical endpoints, and routine follow-up for 1 yr was obtained
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 183
Table 3
Randomized Interventional Trials—30-Day Efficacy Endpoint Events
Death MI Urgent revasc.
Trial (%) (%) (%)
EPIC
Placebo 1.7 8.6 4.5, PCI, 3.6, CABG
Abciximab bolus 1.3 6.2 3.6, PCI, 2.3, CABG
Abciximab bolus + infusion 1.7 5.2 0.8, PCI, 2.4, CABG
EPILOG
Placebo 0.8 8.7 5.2
Abciximab + reduced-dose heparin 0.3 3.7 1.6
Abciximab + standard-dose heparin 0.4 3.8 2.3
EPISTENT
Placebo + stent 0.6 9.6 2.1
Abciximab + stent 0.3 4.5 1.3
Abciximab + PTCA 0.8 5.3 2.1
IMPACT II
Placebo 1.1 8.1 2.8, PCI, 2.8, CABG
Eptifibatide 135/0.5 dose 0.5 6.6 2.6, PCI, 1.6, CABG
Eptifibatide 135/0.75 dose 0.8 6.9 2.9, PCI, 2.0, CABG
ESPRIT
Placebo 0.6 9.7 1.7
a
Eptifibatide 180/2.0/180 dose 0.4 6.2 1.1
a
RESTORE
Placebo 0.7 5.7 4.0, PCI
b
, 1.4, CABG
b
Tirofiban 0.8 4.2 2.3, PCI
b
,
1.1, CABG
b
CAPTURE
Placebo 1.3 8.2 10.9
Abciximab 1.0 4.1 7.8
RAPPORT
Placebo 2.1 4.1 6.6
a
Abciximab 2.5 3.3 1.7
a
ISAR-2
Control 4.5 1.5 5.0
a
Abciximab 2.0 0.5 3.0
a
ADMIRAL
Placebo 6.6 2.6 6.6
Abciximab 3.4 1.3 1.3
CADILLAC
PTCA + Control 2.5 0.8 5.6
PTCA + Abciximab 1.1 0.8 3.4
Stent + Control 2.2 1.0 3.2
Stent + Abciximab 2.7 0.8 1.6
TARGET
Tirofiban 0.5 6.9 0.8
a
Abciximab 0.4 5.4 0.7
a
Abbreviations: CABG, coronary artery bypass graft surgery; MI, myocardial infarction; PCI, percuta-
neous coronary intervention; PTCA, percutaneous transluminal coronary angioplasty; 135/0.5, 135/0/75, and
180/2.0/180 = eptifibatide doses (see text).
a
Revascularization endpoint is Urgent Target Vessel revascularization, compared with Urgent Revascu-
larization for other trials.
b
The RESTORE endpoints listed here are for the published post hoc analysis including only urgent repeat
revascularization, for consistency with the other trials.
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184 Part II / GPIIb/IIIa Blockade During Coronary Intervention
in many of the studies. In EPIC, the earliest of these studies, double blinding was main-
tained and clinical data for all endpoints were obtained for up to 3 yr. Recently, an analy-
sis of long-term mortality outcome of the three major abciximab studies has been reported,
with EPIC data to 7 yr, EPILOG data to 4.5 yr, and EPISTENT data to 3 yr.
A
CUTE ISCHEMIC ENDPOINTS
Rates of the composite endpoint of death or myocardial infarction at 6 mo in the nine
trials without active controls (i.e., excluding TARGET) for which data are available are
summarized in Fig. 3. In general, the treatment effect in reducing these acute ischemic
events that was achieved early (by 30 d) with GPIIb/IIIa blockade was maintained with-
out attenuation over the long term. The same observation held true for the suppression
of urgent revascularization events in those trials in which the urgency of revascularization
procedures was adjudicated over long-term follow-up. In EPILOG, for example, the com-
posite endpoint of death, myocardial infarction, or urgent repeat revascularization was
reduced in the combined abciximab groups compared with placebo from 11.7 to 5.3% at
30 d, from 14.7 to 8.4% at 6 mo, and from 16.1 to 9.6% at 1 yr; thus, the absolute reduction
by abciximab in the composite endpoint (number of events prevented per 100 patients
treated) was remarkably constant, 6.3–6.5, at each of these time points. In the TARGET
trial, rates of death or myocardial infarction at 6 mo were 8.7% vs 7.4% in the tirofiban
and abciximab arms, respectively (p = 0.108). Although the difference in rates of myocar-
dial infarction between abciximab and tirofiban treatment groups was no longer statis-
tically significant by 6 mo, the absolute number of events prevented was unchanged at
these two time points, demonstrating no diminution of the difference between therapies:
Fig. 3. Composite 6-mo endpoint of death or myocardial (re-)infarction event rates for the nine GPIIb/
IIIa interventional trials without active controls (i.e., TARGET excluded) for which data were avail-
able. EPISTENT trial groups compared with reference group of Placebo + Stent. Abbreviations as
for Fig. 2.
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 185
6.9% vs 5.4% ( p = 0.04), absolute difference 1.5% at 30 d; 8.0% vs 6.6% ( p = 0.07), abso-
lute difference 1.4% at 6 mo.
In the CAPTURE trial, the incidences of death or revascularization over 6 mo were not
different among placebo- and abciximab-treated patients. The treatment effect of abcixi-
mab on myocardial infarction rates persisted by 6 mo, but was somewhat attenuated
(8.2% vs 4.1%, absolute 4.1% difference at 30 d; 9.3% vs 6.6%, absolute 2.7% difference
at 6 mo). Such attenuation over long-term follow-up is in contradistinction to the experi-
ence in the other GP IIb/IIIa trials during coronary intervention and may be related to the
severity of the acute ischemic syndrome or to inadequacy of the 1-h postprocedural abci-
ximab infusion in CAPTURE.
M
ORTALITY
The long-term follow-up at 1 yr after randomization in the EPISTENT trial provided
compelling evidence of a complementary clinical benefit of GPIIb/IIIa blockade and
stenting. The combination of stenting and abciximab resulted in a significantly lower
mortality rate than either therapy alone (placebo plus stent, 2.4%; abciximab plus angio-
plasty, 2.1%; abciximab plus stent, 1.0%; hazard ratio = 0.43 for the comparison of abcix-
imab plus stent vs placebo plus stent, p = 0.037). Further evidence for this finding of
a mortality reduction by abciximab during PCI was obtained by pooling the long-term
findings of the different abciximab interventional trials (38). Among all studies using the
bolus and 12-h infusion regimen of abciximab, mortality rates compared with placebo
were significantly diminished by 25–30% for as long as 3 yr (Fig. 4). The mechanism of
mortality reduction with abciximab in these studies remains to be defined. Although the
occurrence of a periprocedural myocardial infarction or urgent revascularization clearly
increased the risk of subsequent death over the ensuing year, 70–75% of the observed
mortality by 1 yr occurred in patients who had not suffered an ischemic event within the early
Fig. 4. Pooled results of mortality reduction over time by abciximab relative to control for all inter-
ventional trials using the bolus and 12-h infusion regimen of abciximab during percutaneous coronary
intervention. Abs ∆, absolute % reduction in mortality; HR, hazard ratio. (Data from ref. 38.)
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186 Part II / GPIIb/IIIa Blockade During Coronary Intervention
period after their index intervention (38). Thus, abciximab did not appear to exert its
mortality benefit exclusively through prevention of early ischemic complications.
A significant reduction in long-term mortality by the small-molecule GPIIb/IIIa inhib-
itors has not been demonstrated; no effects of eptifibatide or tirofiban on death rates were
observed in the IMPACT-II or RESTORE trials. There was, however, a nonsignificant trend
toward mortality reduction at 1 yr with the high-dose eptifibatide regimen in the ESPRIT
trial (placebo 2.0% vs eptifibatide 1.4%; hazard ratio = 0.69; p = 0.28) (39). Moreover, there
were no differences between the tirofiban and abciximab treatment arms with with regard to
1-yr mortality rates in the TARGET trial (1.92% vs 1.74%, respectively), although TARGET
was not statistically powered to assess for equivalence with regard to the infrequent mor-
tality endpoint.
T
ARGET VESSEL REVASCULARIZATION
The 6-mo results of the EPIC trial demonstrated that therapy with abciximab was asso-
ciated with a significant reduction in the need for target vessel revascularization proce-
dures (elective or urgent) at 6 mo, from 22.3% among patients receiving placebo to 16.5%
among those receiving the bolus and infusion of abciximab (26% relative risk reduction,
p = 0.007), a finding that led to speculation that this agent may reduce restenosis follow-
ing coronary intervention. Routine angiographic follow-up was not performed in EPIC;
thus, the influence of abciximab on angiographic restenosis could not be confirmed. A sig-
nificant reduction in the need for late target vessel revascularization procedures by abcixi-
mab was not observed at 6 mo or 1 yr in the subsequent EPILOG trial; with the exception
of ADMIRAL, neither have any of the other interventional trials with GPIIb/IIIa blockade
during balloon angioplasty or stenting demonstrated a significant decrease in “clinical
Fig. 5. Rates of 6-mo target vessel revascularization for the GPIIb/IIIa interventional trials. EPISTENT
trial groups compared with reference group of Placebo + Stent. Abbreviations as for Fig. 3.
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 187
restenosis” (Fig. 5). In the only trial directly comparing two agents, TARGET, differences
between the GPIIb/IIIa inhibitors were not observed: at 6 mo, rates of target vessel revas-
cularization were 7.5 and 8.0% (p = NS) in the tirofiban and abciximab groups, respec-
tively. Angiographic substudies within the EPISTENT, IMPACT II, RESTORE, ISAR-2,
and CADILLAC trials showed no differences among control or abciximab treatment groups
in angiographic measurements of luminal dimensions or restenosis. Moreover, the influ-
ence of 12-h or 24-h infusions of abciximab on in-stent restenosis was assessed among
225 patients in the mechanistic ERASER study utilizing intravascular ultrasound (IVUS)
measurements of in-stent neointimal tissue volume (40). No effect of either abciximab
regimen on neointimal hyperplasia following stenting was observed by IVUS, a finding
confirmed by quantitative coronary angiography.
The only intriguing exception to the apparent lack of effect of GPIIb/IIIa blockade on
restenosis has been suggested in the EPISTENT and ADMIRAL trials among patients
with diabetes mellitus. Rates of target vessel revascularization by 6 mo after stenting were
reduced in diabetic patients from 16.6 to 8.1% (p = 0.021) in EPISTENT and from 37.5
to 13.8% (p = 0.046) in ADMIRAL. The angiographic substudy within EPISTENT con-
firmed a reduction in in-stent neointimal hyperplasia by abciximab in the diabetic sub-
group. Notably, rates of target vessel revascularization at 6 mo were the same (although
relatively low) among diabetics in the abciximab and tirofiban treatment arms of TARGET
(10.8 and 8.8%, respectively, p = 0.257), suggesting that if an anti-restenotic effect of abci-
ximab exists in diabetics, it is probably shared by tirofiban as well.
Safety
The major limitation of abciximab therapy in the first interventional trial, EPIC, was
a substantially increased risk of bleeding: the bolus and infusion regimen of abciximab
was associated with a doubling in the incidence of major bleeding events and the need for
red blood cell transfusions. A high rate of bleeding was also observed in RAPPORT, prob-
ably related to the relatively high heparin dose and long vascular sheath dwell times. During
subsequent trials, in which heparin doses were limited and vascular sheaths removed
early, bleeding rates were diminished in all treatment groups, and appreciable increases
in major hemorrhagic risk were no longer associated with GPIIb/IIIa therapy (Table 4)
Minor bleeding events (defined as gastrointestinal or genitourinary bleeding or hemoglo-
bin drop of 3–5 gm/dL) tended to occur more frequently in these trials among patients
receiving GPIIb/IIIa agents compared with placebo, even with reduced-dose heparin
regimens. In the two recent major stent trials, for example, rates of minor bleeding were
1.7% vs 2.9% in the placebo and abciximab groups of EPISTENT and 1.7% vs 2.8% in
the placebo and eptifibatide groups of ESPRIT. Similarly, although there were no differ-
ences between tirofiban and abciximab treatment groups in rates of major bleeding (0.9
and 0.7%, respectively), abciximab therapy was associated with more minor bleeding in
that trial (2.8% vs 4.3%, p < 0.001).
Thrombocytopenia occurred infrequently but was somewhat increased among patients
receiving GPIIb/IIIa antagonists, particularly abciximab (Table 5). An increased risk of
severe thrombocytopenia (platelet count < 50,000 mm
−3
) occurred almost exclusively
with abciximab therapy, with rates as high as 1.0–1.8%. In the TARGET trial, severe throm-
bocytopenia occurred in 0.1 and 0.9% of patients randomized to tirofiban and abciximab,
respectively (p < 0.001).
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188 Part II / GPIIb/IIIa Blockade During Coronary Intervention
Table 4
Rates of In-Hospital of 30-Day TIMI Major Bleeding and Transfusions
Major bleeding
a
Transfusions
Trial (%) (%)
EPIC
Placebo 6.6 7.0
Abciximab bolus 10.9 13.2
Abciximab bolus + infusion 14.0 15.4
EPILOG
Placebo 3.1 3.9
Abciximab + reduced-dose heparin 2.0 1.9
Abciximab + standard-dose heparin 3.5 3.3
EPISTENT
Placebo + stent 2.2 2.2
Abciximab + stent 1.5 2.8
Abciximab + PTCA 1.4 3.1
IMPACT II
Placebo 4.8 5.2
Eptifibatide 135/0.5 dose 5.1 5.6
Eptifibatide 135/0.75 dose 5.2 5.9
ESPRIT
Placebo 0.4 1.0
Eptifibatide 180/2.0/180 dose 1.0 1.4
RESTORE
Placebo 2.1 2.2
b
Tirofiban 2.4 3.5
b
CAPTURE
Placebo 2.5 3.4
Abciximab 4.1 7.1
RAPPORT
Placebo 9.5 7.9
Abciximab 16.6 13.7
ISAR-2
Control N/A 4.5
Abciximab N/A 3.5
ADMIRAL
Placebo 0 N/A
Abciximab 0.7 N/A
CADILLAC
PTCA + Control 0.6 3.7
PTCA + Abciximab 0.4 5.1
Stent + Control 0.2 4.1
Stent + Abciximab 0.8 5.0
TARGET
Tirofiban 0.9 1.2
Abciximab 0.7 1.5
Abbreviations: 135/0.5, 135/0/75, and 180/2.0/180 = eptifibatide doses (see text); N/A, not available.
a
Major Bleeding defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria (28) as intracranial
hemorrhage or bleeding associated with a decrease in hemoglobin of ≥5 g/dL.
b
Transfusion rates in RESTORE reported only for >2 U.
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Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 189
Table 5
Rates of Thrombocytopenia
Control GPIIb/IIIa inhibitor
Trial Agent (%) (%)
Moderate thrombocytopenia (platelet count < 100,000 mm
−3
)
EPIC Abciximab 3.4 3.6 (bolus)
5.2 (bolus + infusion)
EPILOG Abciximab 1.5 2.6 (std. dose heparin)
2.5 (low-dose heparin)
EPISTENT Abciximab 0.6 3.1 (plus stent)
2.9 (plus PTCA)
CAPTURE Abciximab 1.3 5.6
RAPPORT Abciximab 2.9 5.0
ADMIRAL Abciximab 1.3 4.7
CADILLAC Abciximab 2.0 4.0
IMPACT II Eptifibatide 2.7 3.2 (135/0.5 dose)
2.8 (135/0.75 dose)
RESTORE
a
Tirofiban 0.9 1.1
Severe thrombocytopenia (platelet count < 50,000 mm
−3
)
b
EPIC Abciximab 0.7 0.4 (bolus)
1.6 (bolus + infusion)
EPILOG Abciximab 0.4 0.9 (std. dose heparin)
0.4 (low-dose heparin)
EPISTENT Abciximab 0 1.1 (plus stent)
0.9 (plus PTCA)
CAPTURE Abciximab 0.3 1.8
ADMIRAL Abciximab 1.3 1.3
IMPACT II Eptifibatide 0.6 0.2 (135/0.5 dose)
0.4 (135/0.75 dose)
ESPRIT Eptifibatide 0 0.2
RESTORE Tirofiban 0.1 0.2
a
Reported in RESTORE for platelet count < 90,000 mm
−3
.
b
Reported in ESPRIT trial for platelet count < 20,000 mm
−3
.
Coronary Intervention in Trials of Unstable Angina
Six large-scale trials have assessed GPIIb/IIIa inhibition among patients with unstable
angina or non-Q-wave myocardial infarction in whom percutaneous revascularization
was not mandated. In three of these trials, PURSUIT (41) and PRISM PLUS (42), and
PARAGON B (43), a substantial number of patients underwent early coronary interven-
tion while on study drug infusion, providing important information regarding the efficacy
of these agents as preprocedural and postprocedural therapy. In PURSUIT, 9461 patients
were randomized to receive placebo or eptifibatide (180 µg/kg bolus, then 2.0 µg/kg/min
infusion for 72–96 h) in addition to heparin or aspirin; of these, 1228 underwent percuta-
neous revascularization within the first 72 h (while receiving study drug) (41). Eptifibatide
was associated with a significant reduction in the risk of myocardial infarction prior to
the revascularization procedure (5.5% vs 1.8%, p < 0.001), as well as a significant reduction
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