Recommendations

ACC - www.acc.org
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Smith et al. 2005
ACC/AHA/SCAI Practice Guidelines
67
Table 24b. Subgroup Analyses for Mortality After PCI in Trials of Glycoprotein IIb/IIIa Inhibitors (See Table 24a for eligible
trials)
30 Days 6 Months
No. of Studies RR (95% CI) No. of Studies RR (95% CI)
20 (20 137)* 0.69 (0.53 to 0.90)* 14 (15 651)* 0.79 (0.64 to 0.97)*
Population
AMI 6 (3355) 0.69 (0.45 to 1.05) 6 (3355) 0.76 (0.55 to 1.05)
Mixed 2 (4240) 0.95 (0.54 to 1.68) 2 (4240) 0.97 (0.65 to 1.44)
Non-AMI 12 (12 542) 0.59 (0.39 to 0.89) 6 (8056) 0.71 (0.49 to 1.03)
Procedure
Stent 7 (5736) 0.69 (0.43 to 1.09) 7 (5736) 0.70 (0.49 to 1.01)
Other 13 (14 401) 0.70 (0.51 to 0.96) 7 (9915) 0.84 (0.65 to 1.09)
Postprocedure
Heparin 7 (4791) 0.72 (0.47 to 1.09) 5 (4548) 0.83 (0.60 to 1.13)
No heparin 13 (15 346) 0.68 (0.49 to 0.95) 9 (11 103) 0.77 (0.58 to 1.01)
Agent
Abciximab 14 (11 606) 0.69 (0.51 to 0.94) 12 (11 446) 0.77 (0.61 to 0.96)
Tirofiban 2 (2234) 1.05 (0.42 to 2.61) 1 (2141) 1.27 (0.65 to 2.48)
Eptifibatide 4 (6297) 0.60 (0.33 to 1.06) 1 (2064) 0.56 (0.24 to 1.34)
AMI indicates acute myocardial infarction; CI, confidence interval; No., number; and RR, risk ratio (fixed effects).
There was no statistically significant heterogeneity in any case, and random effects estimates were similar (data not shown).
*Refers to all patients.
Reprinted with permission from Karvouni et al. J Am Coll Cardiol 2003;41:6-32 (701).
The clinical utility of eptifibatide, a short-acting cyclic heptapeptide
that also inhibits the GP IIb/IIIa receptor, was evaluated
in the Integrilin to Manage Platelet Aggregation to
prevent Coronary Thrombosis-II (IMPACT-II) trial, a double-blind,
randomized, placebo-controlled multicenter trial
that enrolled 4010 patients undergoing coronary angioplasty
(198). Patients were assigned to treatment with aspirin,
heparin and placebo, aspirin, heparin, and eptifibatide bolus
(135 mcg per kg) followed by a low-dose eptifibatide infufor
the CAPTURE investigators, also reported that among
the 1265 patients with UA enrolled in the CAPTURE trial,
troponin T and CK-MB from 890 patients correlated with
subsequent 6-month adverse cardiac risk. In patients without
elevated troponin T levels, there was no benefit of treatment
with respect to the relative risk of death or MI at 6 months
(OR 1.26, CI 95% 0.74 to 2.31; P equals 0.47). Serum troponin
T level, which is considered to be a surrogate marker
for thrombus formation, identified a high-risk subgroup of
patients with refractory UA suitable for coronary intervention
who would particularly benefit from antiplatelet treatment
with abciximab (192).
One putative limitation of abciximab is the potential for
immune-mediated hypersensitivity reactions after subsequent
readministration. Thrombocytopenia after readministration
occurs in 3.5% to 6.3% of patients, which is similar to
the rate of occurrence in patients receiving abciximab for the
first time. Therefore, the absence of thrombocytopenia after
a first abciximab exposure does not guarantee protection
against its occurrence upon re-exposure. Moreover, the
prevalence of severe thrombocytopenia (2.8%) and profound
thrombocytopenia (2.0%) is greater with readministration
than the incidence observed after first-time administration
(1.0% and 0.4% for severe and profound thrombocytopenia,
respectively) (202). With the first administration, human
antichimeric antibodies (HACA) form in approximately 6%
of patients (702). The implications of HACA, however, are
unclear. Among 500 patients enrolled in the ReoPro
Readministration Registry (R3), there were no cases of anaphylaxis
or other allergic manifestations whether or not
HACA was present, and HACA was not predictive of any
other measure of complication or success. From the R3
study, HACA has been shown to be an IgG (not IgE)
immunoglobulin that does not neutralize abciximab. The
more worrisome clinical phenomenon associated with readministration
is the potential for increased rates of thrombocytopenia.
In the 500-patient R3, a 4.4% incidence in thrombocytopenia
(to a platelet count of less than 100 × 109 per
liter) was observed, with half of the patients developing
acute profound thrombocytopenia (to a platelet count of less
than 20 × 109 per liter). This potential complication should
always be monitored when treating a patient with abciximab
(194-197). Abciximab readministration poses greater risk
within 2 weeks of original abciximab dose.
6.2.2.2. Eptifibatide