Discussion
Our study showed that in STEMI patients who underwent PPCI, although
Eptifibatide maintenance dose infusion, causes a significant reduction
in re-hospitalization, re-infarction and TLR, it does not cause a
significant reduction in MACE.
The most studied GP IIb/IIIa inhibitor in patients with STEMI who
undergo PPCI is Abciximab (8). Although previous large studies showed
that administration of Abciximab in patients undergoing PPCI due to
STEMI reduces death, reinfarction and ischemic events (19, 20),
subsequent studies showed that its administration especially in patients
whom receive thienopyridine drugs at the same time, does not
significantly reduce death and re-infarction (21,22). However, the
results of our study showed that the administration of Eptifibatide in a
subgroup of patients with hypertension and hyperlipidemia reduces MACE.
Whether this effect of the drug is related to the primary antiplatelet
effect of Eptifibatide or the non-specific anti-inflammatory properties
of it is not determined by our study.
In 2010, Zeymer and colleagues in the EVA-AMI Trial showed that
Eptifibatide infusion, as an adjunct to PPCI in the treatment of STEMI,
is as effective as Abciximab, and even the rate of re- infarction was
significantly lower with Eptifibatide, while There was no significant
difference of the bleeding rate between the two groups (23). This
finding is consistent with the lower rate of re-infarction in our
intervention group.
So far, many studies have been published on the adjuvant effect of
Eptifibatide infusion in patients undergoing PCI. One of the most
important studies is the ESPRIT Trial. The findings of this study showed
that the administration of Eptifibatide leads to a significant reduction
of 48-hour and 30-day MACE (combination of death, myocardial infarction
and TVR) (24). The inconsistency of the results of our study with ESPRIT
Trial can be due to the smaller sample size of our study (264 patients
vs. 2064 patients) and also the shorter infusion time of this drug in
our study (12 hours vs. 24-18 hours) and as a result receiving a lower
dose of the drug. GP IIb/IIIa inhibitors block the binding of
circulating fibrinogen and von Willebrand factor to the GP IIb/IIIa
receptor thus preventing the cross-linking of platelets necessary for
aggregation and thrombosis. These agents have also been shown to
disaggregate freshly formed, platelet-rich thrombi in a “dose-dependent
manner” ranging from no disaggregation at low doses up to significant
disaggregation at clinically relevant doses (25).
Most of the studies conducted on Eptifibatide are on patients who are
candidates for PCI in the context of NSTE ACS. To our knowledge, few
clinical trials have been conducted on the effect of Eptifibatide in
patients undergoing PPCI due to STEMI. Among these clinical trials is a
study that was conducted between 2000-2009 in the United States and
showed that the administration of Eptifibatide reduces mortality in
STEMI patients who undergo PPCI (25), while the study by Le May et al,
and the study of Shariati et al, showed that the administration of this
drug does not reduce MACE (combined mortality and recurrent myocardial
infarction) (13,26). These observations however have not been fully
supported by a retrospective analysis of clinical outcomes in the ESPRIT
trial, accepting that this was not a primary PCI study and not everyone
in the preloading group received the 600mg dose of Clopidogrel, the
study demonstrated that the efficacy of Eptifibatide was maintained
irrespective of Thienopyridine preloading.
Also, our study showed that Eptifibatide administration does not
increase major and minor bleeding and cerebrovascular events. One of the
reasons for the low rate of bleeding in the present study is the careful
selection of patients based on the inclusion and exclusion criteria,
which reduces the chance of bleeding. The homogeneity of the two groups
in terms of the amount of major and minor bleeding shows that the
possibility of bleeding complications should not prevent the
administration of this drug infusion in high-risk patients.
Our study shows that the adjunctive use of Eptifibatide in patients
presenting with STEMI and undergoing PPCI treatment does not reduce MACE
but reduces re-hospitalization, re-infarction and TLR, and may be
associated with improved clinical outcomes, especially as it does not
increase the risk of bleeding and cerebrovascular events. In future
studies in STEMI patients (an area where the effect of Eptifibatide has
not been sufficiently investigated), with a larger sample size and with
a higher power, its generalizability to the community and its validity
can be improved.