Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future

Abstract

Coronary artery disease and acute myocardial infarction still represent the leading cause of mortality in developed countries. Therefore, great efforts have been made in the last decades to improve reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite optimal epicardial recanalisation, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. The adjunctive use of glycoprotein (GP) IIb-IIIa inhibitors may certainly contribute in the reduction of such complications, especially when administered in the early phase of infarction. In fact, in this phase a larger platelet composition of the thrombus and the presence of a larger amount of viable myocardium, as compared to a delayed phase, may increase the benefits from this therapy and counterbalance the potential higher risk of bleeding. A large body of evidence has been accumulated on the benefits from GP IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients and as upstream strategy. Therefore, based on current available data, GP IIb-IIIa inhibitors can be recommended as early as possible (upstream strategy) among high-risk patients, such as those with advanced Killip class or anterior myocardial infarction (MI), and those presenting within the first three hours. Even though it is not universally accepted, in our opinion this strategy should be implemented in a pre-hospital setting (in ambulance) or at first hospital admission (Emergency Room or Coronary Care Unit, irrespective of whether they are in the spoke or hub hospitals). Peri-procedural intracoronary administration of GP IIb-IIIa inhibitors has not provided additional benefits as compared to intravenous administration and therefore cannot be recommended. Even though the vast majority of trials have been conducted with abciximab, several meta-analyses comparing small molecules (mainly high-dose tirofiban rather than eptifibatide) versus abciximab showed similar angiographic and clinical results between the molecules. Several recent investigations and meta-analyses have documented the higher risk of stent thrombosis associated with bivalirudin as compared to unfractionated heparin (UFH). Being that these results are independent from the use of GP IIb-IIIa inhibitors, UFH should still remain the anticoagulation therapy of choice in ST-segment elevation myocardial infarction (STEMI) patients. Minimisation of bleeding complications by extensive use of the radial approach, in the setting of STEMI, may further contribute to the adoption of a more aggressive antithrombotic and antiplatelet therapy incorporating the use of GP IIb-IIIa inhibitors. The establishment of dedicated networks for STEMI, and the large STEMI campaign, will certainly contribute to increase the proportion of patients presenting at first medical contact within the early phase (3 h) of infarction and therefore highly suitable for a more aggressive pharmacoinvasive approach with upstream administration of GP IIb-II...

Comprehensive analysis clinical effectiveness of Tirofiban for patients with non-ST-elevation acute coronary syndrome

“…And the GP IIb/IlIa receptor is only found in the platelet and macrophage lineage, this feature enables specific treatment of its antagonists, without fearing of causing a wide range of side effects [24]. The appearance of platelet GPIIb/IlIa receptor antagonists is the milestone event in the history of ainti-platelet drug development [25]. Compared with the monoclonal antibody Fab fragment abciximab, small molecule GPI GP IIb/ IIIa receptor antagonist have a higher binding specificity, stronger role, and reversible combination, so, adverse reactions can be discontinued soon by immediately discontinued the drag, and as a synthetic peptide, themselves almost without antigen, do not cause allergic reactions, can be a long time or repeated treatment.…”

Contemporary Management of ST-Elevation Myocardial Infarction

“…It is not routinely recommended if bivalirudin is chosen instead of heparin, only as ''bail-out'' therapy [15]. Other GPIIb/IIIa inhibitors, mainly tirofiban but also eptifibatide, have similar evidence for reducing ischaemic events [35].…”

Impact of active smoking on the immature platelet fraction and its relationship with the extent of coronary artery disease

“…1 In fact, smoking has been established to enhance oxidative stress and low-grade inflammation, increasing radical oxygen production (ROS) and triggering the response of the immune system and platelets, the major actors in the development of atherothrombotic events. 2 Great interest has been recently focused on platelet subpopulations, and in particular on the role of reticulated platelets, the younger platelets lastly released from the bone marrow, that have been hypothesized as having an increased aggregating potential and then a larger impact on the atherothrombotic processes. However, contrasting data have been reported on the association between reticulated platelets and coronary artery disease (CAD).…”