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.