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Current Role of Platelet Glycoprotein Iib/Iiia Inhibition in the Therapeutic Management of Acute Coronary Syndromes in the Stent Era

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Current Role of Platelet Glycoprotein Iib/Iiia Inhibition in the Therapeutic Management of Acute Coronary Syndromes in the Stent Era Journal of Cardiology & Current Research Current Role of Platelet Glycoprotein IIb/IIIa Inhibition in the Therapeutic Management of Acute Coronary Syndromes in the Stent Era Review Article Abstract The pathophysiology of acute coronary syndromes (ACS) is characterized by Volume 5 Issue 5 - 2016 disruption of atherosclerotic plaques, activation and aggregation of platelets, and formation of an arterial thrombus. Thrombus formation can result in 1 either transient or persistent occlusion giving rise to the spectrum of ACS. This Department of Health Sciences’s Investigation, Sanatorio Metropolitano, Fernando de la Mora, Paraguay syndrome defines rapidly evolving symptoms of myocardial ischemia ranging 2Cardiology Division, First Department of Internal Medicine, from unstable angina pectoris to non-Q-wave myocardial infarction to Q-wave Clinic Hospital, Asunción National University, San Lorenzo, myocardial infarction. An early pharmacological strategy to reduce ischemic Paraguay complications of PCI was the use of parenteral glycoprotein (GP) IIb/IIIa inhibitors. *Corresponding author: Osmar Antonio Centurión, Professor of Medicine, Asuncion National University, The benefit of GP IIb/IIIa inhibitors in early studies was driven primarily by Department of Health Sciences’s Investigation, Sanatorio reductions in periprocedural myocardial infarction. Advances in both stent Metropolitano, Teniente Ettiene 215 c/ Ruta Mariscal design and adjunct pharmacology have led to improved outcomes in ACS and a Estigarribia,Fernando de la Mora, Paraguay, Tel: 595-21- diminished role for GP IIb/IIIa inhibitors as reflected in current PCI guidelines. 498200; Fax: 595-21-205630; Email: Current medical therapy with aspirin, clopidogrel, ticagrelol, prasugrel, and heparin provides important therapeutic benefits. The platelet GP IIb/IIIa receptor antagonists, by blocking the final common pathway of platelet aggregation, Received: March 07, 2016 | Published: May 03, 2016 are a breakthrough in the management of ACS. Several large multicenter trials have evaluated the platelet GP IIb/IIIa antagonists with and without heparin undergoing PCI or not. There was a significantly reduced incidence in the cardiac ischemic events. The clinically important benefit persisted at 3 years of follow- up. In addition to maintaining epicardial wall vessel patency, it was shown an improvement in microvascular perfusion and myocardial function as assessed by peak coronary flow velocity and regional wall motion. Despite the success of abciximab in preventing ischemic events after PCI, the use of intravenous, small-molecule GP IIb/IIIa antagonists, and the intention to broaden the clinical indication have produced varied results. Mechanisms contributing to these heterogeneous outcomes may include the possibility of pro- thrombotic events, as well as, normal variation in platelet or receptor number, differences in receptor activity, and interpatient variation in pharmacological dose response. Trials investigating the role of intravenous small-molecule GP IIb/IIIa antagonists underline the importance of adequate higher and effective dosing. These trials highlight the use of suboptimal dose as the cause for the poor outcome in some instances. Despite the heterogeneous outcome, these agents still have potential advantages in patients with high clinical risk but low bleeding risk. Adjunctive platelet GP IIb/IIIa receptor inhibition has proved beneficial effects in the setting of PCI, and still has a place as bailout therapy for periprocedural PCI complications in ACS patients, such as those patients with large thrombus, with stent thrombosis, and refractory no-reflow phenomenon following PCI. Keywords: Platelet GP IIb/IIIa antagonists; Percutaneous coronary interventions; Acute coronary syndromes Submit Manuscript | http://medcraveonline.com J Cardiol Curr Res 2016, 5(5): 00175 Current Role of Platelet Glycoprotein IIb/IIIa Inhibition in the Therapeutic Management Copyright: 2/14 of Acute Coronary Syndromes in the Stent Era ©2016 Centurión Introduction in the platelet membrane [10]. The GP IIb/IIIa domains responsible Although there are major advances in the treatment and composed of a globular head and two flexible tails that are imbibed management of cardiovascular diseases, ischemic heart disease are characterized by their ability to recognize the peptide sequence continues to be the leading cause of mortality and morbidity RGD.for binding The RGD adhesive recognition proteins sequence have been was identified originally and described in general for worldwide. Ischemic heart disease affects nearly 16 million persons aged 20 years and older in the USA. More than 2 million Willebrand factor, vitronectin, and thrombospondin [11]. If two cases of unstable angina (UA), and nearly 4 million cases of acute activatedfibronectin platelets but is now with known functional to be GP present IIb/IIIa in fibrinogen,receptors each von myocardial infarction (AMI) occur annually in the world. These numbers will likely increase over the next decade due to aging between the two platelets. When these processes of aggregation population (1-5). The prevalence of patients who have survived arebind repeated the same thousands fibrinogen of molecule, times, a thrombus a fibrinogen is generated. bridge is createdIt is the an episode of AMI is estimated at 15 million, these patients are chief receptor responsible for platelet aggregation by its ability to at high risk to develop additional acute events. Although, the incidence of UA is lower than that of AMI, its prevalence is likely to leading ultimately to thrombus formation. However, this receptor be higher because patients are more likely to survive an episode bind soluble fibrinogen, which forms bridges between platelets of UA, and these patients are also at high risk for the occurrence of stimulated by agonists and undergoes a conformational change. additional acute coronary syndrome (ACS). Sinceremains GP unableIIb/IIIa toreceptors bind fibrinogen are unique unless to platelets, the platelet and areis first the Common antiplatelet agents such as aspirin and ticlopidine, clopidogrel, ticagrelol prasugrel, and antithrombin agents such these factors make these receptors an extremely favorable target as hirudin and heparin, act by inhibiting different pathways of forfinal therapeutic common pathwaypharmacologic for platelet blockade aggregation (Figure 1) by [12,13]. all agonists, platelet activation in a different manner. This may account for ABCIXIMAB (Murine monoclonal antibodies 7E3): More the limited ability of these agents to prevent platelet aggregation, than three decades ago, Coller [14] produced a mouse monoclonal since other avenues of activation are left undisturbed [1-3]. The antibody against the GP IIb/IIIa integrin receptor [14]. The Coller antibody, termed abciximab or 7E3, has a molecular weight of for all platelet aggregation suggests the possibility that agents designedcritical role to ofantagonize the GP IIb/IIIa this receptor receptor may as final be thecommon most pathwayeffective for the GP IIb/IIIa receptor, two properties that make 7E3 an type of agents for preventing platelet aggregation and, therefore, extremely47.6 kD and attractive exhibits therapeutic both a high-affinity agent for andthe blocking absolute of specificity adhesive thrombosis. Regardless of the stimulus for platelet activation, GP IIb/IIIa antagonists inhibit thrombosis by preventing GP IIb/IIIa receptor in either the active or inactive state with additionalproteins [15-18]. activity Abciximab against the shows vitronectin a high bindingreceptor affinity and possibly for the MAC-1 [19, 20]. The vitronectin receptor plays a role in cell thrombusfibrinogen fromformation binding [4-8]. to the Platelets platelet areGP IIb/IIIaknown receptor,to play thean adhesion, migration and proliferation. The vitronectin receptor importantfinal common role pathway in the pathogenesis of platelet aggregation of ACS. However, and subsequent the high blockade can prevent smooth muscle cell hyperplasia, and MAC- levels of platelet inhibition attainable with GP IIb/IIIa antagonists 1 inhibition can prevent stimulated monocyte-induced smooth have failed to dramatically improve clinical outcomes outside of muscle cell apoptosis. Abciximab has almost no renal excretion, percutaneous coronary intervention (PCI). Therefore, this paper but is cleared rapidly from the plasma, however, it is detectable will concentrate and emphasize on the role of these anti-platelet bound to circulating platelets for at least 21 days [21, 22]. Small-Molecule Agents plateletagents in GP the IIb/IIIa setting studieswhere thewithout most PCIbenefit are isbeyond achieved, the that scope is, ofduring this report.PCI. Although, Thus, the some aim non-PCI of this manuscripttrials are briefly is to mentioned,review the a) Asp (KGD) amino acid sequence. It has a molecular weight of of ACS in the setting of PCI. 0.832Eptifibatide kD and is 50% a cyclic renal heptapeptide excretion [23]. based upon the Lys-Gly- current beneficial effects of GP IIb/IIIa inhibition in the treatment Platelet GP IIb/IIIa receptor inhibitors molecular weight of 0.495 kD and 40-70% renal excretion Platelet GP IIb/IIIa receptor is distributed widely on platelet b) [24].Tirofiban is tyrosine-derivative nonpeptide mimetic with surfaces. There are an estimated 40,000 to 80,000 GP IIb/IIIa receptors per platelet, making it the most numerous receptors on the platelet membrane surface [3]. Platelet aggregation is weight of 0.468 kD and
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