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Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with...
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Background Obesity is a predisposing factor for atherosclerotic coronary arterial disease. Many studies have shown a protective effect of obesity for major adverse cardiovascular events after percutaneous coronary intervention (PCI).
Aim The main purpose of this article is to assess the clinical characteristics, invasive angiographic features, and...
Citations
... В то же время в недавно проведенном крупном регистровом исследовании, включающем более 110 000 пациентов, было продемонстрировано, что в клиниках, где ИГ IIb/IIIa применялись рутинно (более 75% всех случаев острого ИМпST) в сравнении с клиниками, где данные препараты применялись избирательно (менее 25% всех случаев острого ИМпST), показатели летальности через 1 год были статистически значимо ниже (9,7 против 11%, р < 0,001). При этом использование ИГ IIb/IIIa являлось независимым предиктором снижения отдаленной летальности [18]. ...
Aim: To evaluate the efficacy and safety of the preventive use of glycoprotein (GP) IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction (STEMI) and a high risk of « no-reflow » phenomenon. Material and Methods . A total of 100 patients were included in the study. For all patients, the risk of no-reflow was calculated using a previously developed scoring system. In case of high risk, GP IIb/IIIa inhibitors were administered according to the decision of the interventional cardiologist. The rate of no-reflow as well as the rates of death, recurrent myocardial infarction and stent thrombosis were analyzed. Results. High risk of no-reflow was determined in 37 patients, low risk of no-reflow – in 63 patients. In the high-risk group 22 patients (59.5%) GP IIb/IIIa inhibitors were preventively used. In these patients, the frequency of no-reflow was lower compared with high-risk patients who did not receive preventive GP IIb/IIIa inhibitors (9.1 vs. 46.7%, p = 0.017). With the preventive use of GP IIb/IIIa inhibitors in high-risk patients, the rates of no-reflow (9.1 vs. 11.1%, p = 1.000) and angiographic success of percutaneous coronary intervention (72.7 vs. 84.1%, p = 0.341) were comparable with low-risk patients. Conclusion. The preventive use of GP IIb/IIIa inhibitors in patients with STEMI and a high risk was associated with reduction of « no-reflow » . In the prophylactic use of GP IIb/IIIa inhibitors in patients with STEMI and a high risk of no-reflow, the results of their treatment were comparable to patients with a low risk of no-reflow.
... A meta-analysis of 31,402 NSTE-ACS patients not referred to early PCI from six randomized trials showed that GPI were associated with lower rates of death or MI, with an increase in major bleeding as compared to placebo or active control [34]. However, no evidence supports upstream GPI in contemporary patients referred to early angiography and treated with potent P2Y 12 inhibitors, and therefore this practice is discouraged by current recommendations [35,36]. ...
Introduction:
Non-ST-segment elevation acute coronary syndromes (NSTE-ACS), including non-ST-segment-elevation myocardial infarction (NSTEMI) and unstable angina, represent a leading cause of mortality worldwide, with important socio-economic consequences. NSTEMI accounts for the majority of acute coronary syndromes and usually develops on the background of a nonocclusive thrombus. We searched for relevant literature in the field in PubMed and clinicaltrials.gov as of July 2022.
Areas covered:
A number of pharmacotherapies are currently available for treatment and secondary prevention, mainly including antithrombotic, lipid-lowering and anti-inflammatory drugs. Pretreatment with aspirin, anticoagulant and statin therapy is of key importance in the preprocedural phase, while pretreating with an oral P2Y12 inhibitor is not routinely indicated in patients undergoing early invasive management. For patients undergoing percutaneous coronary revascularization, pharmacotherapy essentially consists of antithrombotic drugs, which should be carefully selected. Finally, antithrombotic, lipid-lowering and anti-inflammatory drugs are important components of long-term secondary prevention after a NSTE-ACS.
Expert opinion:
This article reviews the evidence supporting recommendation on pharmacotherapy in patients presenting with a NSTE-ACS. Several randomized clinical trials are still ongoing and are expected to further inform scientific knowledge and clinical practice, with the final aim to improve the treatment of NSTE-ACS patients.
... 17,18 In contrast, parenteral platelet glycoprotein IIb/IIIa inhibitors (GPI) circumvent the need for gastrointestinal absorption, achieve immediate and higher-grade antiplatelet effects against all platelet activators, and show improved patency of the infarct-related artery before PCI. [19][20][21] More importantly, pre-hospital GPI treatment in patients with STEMI led to improved clinical outcomes without an increase in severe bleeding. [20][21][22][23][24] Time from symptom onset to GPI administration was significantly associated with higher patency of the culprit artery and with ST-elevation resolution, with greater improvement in reperfusion in the lowest time quartiles as well as lower occurrence of death. ...
... 27 Currently, pre-hospital GPI administration is not considered standard care for STEMI in North America or Europe, despite evidence of a mortality benefit when used early in patients with STEMI undergoing primary PCI. 25 This may be partly explained by the unfavorable pharmacodynamic and structural profile of currently available intravenous GPIs, which are associated with an increased risk of bleeding complications and thrombocytopenia. 19 Also, the lack of strong evidence supporting pre-hospital use of GPI may be due to results of studies that randomized patients too late (>150 minutes after symptom onset), used prolonged post-bolus drug infusion, and used femoral access that resulted in higher risk of bleeding. 28,29 Another disadvantage of current GPIs is that they require continuous intravenous infusion with an electronic syringe pump, which cannot be universally performed by ambulance services. ...
Background:
Early and complete restoration of target vessel patency in ST-elevation myocardial infarction (STEMI) is associated with improved outcomes. Oral P2Y12 inhibitors have failed to demonstrate either improved patency or reduced mortality when administered in the pre-hospital setting. Thus, there is a need for antiplatelet agents that achieve prompt and potent platelet inhibition, and that restore patency in the pre-hospital setting. Zalunfiban, a novel subcutaneously administered glycoprotein IIb/IIIa inhibitor designed for pre-hospital administration, has shown to achieve rapid, high-grade platelet inhibition that exceeds that of P2Y12 inhibitors. Whether pre-hospital administration of zalunfiban can improve clinical outcome is unknown.
Hypothesis:
The present study is designed to assess the hypothesis that a single, pre-hospital injection of zalunfiban given in the ambulance, in addition to standard-of-care in patients with STEMI with intent to undergo primary percutaneous coronary intervention (PCI) will improve clinical outcome compared to standard-of-care with placebo.
Study design:
The ongoing CELEBRATE trial (NCT04825743) is a phase III, randomized, double-blinded, placebo-controlled, international trial. Patients with STEMI intended to undergo primary PCI will receive treatment with a single subcutaneous injection containing either zalunfiban dose 1 (0.110 mg/kg), zalunfiban dose 2 (0.130 mg/kg) or placebo, and the study drug will be administered in the ambulance before transportation to the hospital. A target of 2499 patients will be randomly assigned to one of the treatment groups in a 1:1:1 ratio, i.e., to have approximately 833 evaluable patients per group. The primary efficacy outcome is a ranked 7-point scale on clinical outcomes. The primary safety outcome is severe or life-threatening bleeding according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria.
Summary:
The CELEBRATE trial will assess whether a single pre-hospital subcutaneous injection of zalunfiban in addition to standard-of-care in patients with STEMI with intent to undergo primary PCI will result in improved clinical outcome.
... In the 2014 ACC/AHA guidelines for elective PCI in SCAD patients, GPIIb/IIIa inhibitors should be considered for patients without pretreatment of clopidogrel (8). By means of rapid and potent platelet inhibition (9), tiro ban is recommended for bail-out if there is evidence of no-re ow or a thrombotic complication, and may also be used for high-risk PCI in patients who were not pretreated with P2Y12 inhibitors according to the 2020 ESC/EACTS Guidelines on myocardial revascularization (10). However, the use of GPIIb/IIIa inhibitors is restricted for the risk of thrombocytopenia (11) and severe bleeding (12), which was a strong predictor of early mortality (10). ...
Background
There is no consensus on reductions of ischemic events and bleeding risks of tirofiban for patients receiving planned percutaneous coronary intervention (PCI) yet. In this study, we aim to investigate the real-world efficacy and safety of tirofiban treatment on patients undergoing planned PCI during hospital course and explore potential population who could benefit from tirofiban.
Methods
This real-world study included 1311 patients who received planned PCI and implanted stents. Demographic and clinical characteristics were compared between patients who received tirofiban treatment (n = 829) and those were not given tirofiban as control (n = 482). Correlation of tirofiban and outcome in hospital level was assessed using logistic regression analysis.
Results
More tirofiban patients had multivessel disease and multiple stents implantation. On logistic regression analysis, there was no significant association between the usage of tirofiban and bleeding events (OR [95%CI] = 1.36 [0.65,3.06], p = 0.433), major adverse cardiac and cerebrovascular events (MACCE) (OR [95%CI] = 1.37 [0.65, 3.06], p = 0.425) or net adverse cardiac and cerebrovascular events (NACCE) (OR [95%CI] = 1.01 [0.61, 1.71], P = 0.963). In subgroup analysis, tirofiban used among patients with higher D-dimer level (D-dimer ≥ 0.5 g/ml FEU) was less likely to be associated with MACCE (OR = 0.51 vs OR = 4.59, p for interaction = 0.031).
Conclusions
The use of tirofiban did not decrease MACCE or NACCE during hospital course among patients undergoing planned PCI, however, the risk of bleeding was not increased. Tirofiban receipts were prone to severe illness and complex PCI. Conferring no harm but potential benefits, the use of tirofiban could be considered for patients who received planned PCI and present with comorbidities and complex coronary lesions.
... The recommended dose for tirofiban is 0.1 mcg/kg/min and 2 mcg/kg/min for eptifibatid. It should be discontinued four to six hours prior to surgery (34). P2Y12 inhibitor cangrelor should be started at least 48 hours after discontinuation of P2Y12 inhibitor and stopped 1-6 hours before surgery. ...
... P2Y12 inhibitor cangrelor should be started at least 48 hours after discontinuation of P2Y12 inhibitor and stopped 1-6 hours before surgery. The recommended dose is 0.75 μg/kg/min (34,35). ...
... The onset of platelet inhibition effect follows almost immediately after bolus administration [107,108]. The rapid inactivation of circulating cangrelor (3-6 minutes) causes a swift offset of antiplatelet effect returning to baseline levels within 30-60 minutes after drug discontinuation, and therefore requires timely co-administration with an oral P2Y 12 inhibitor [106,109,110]. Since cangrelor directly inhibits the active metabolite of thienopyridines from binding to the P2Y 12 receptor, timely coadministration of ticagrelor is recommendable over clopidogrel or prasugrel [107,[111][112][113]. Due to its faster onset of antiplatelet effect compared with oral P2Y 12 inhibitors, cangrelor represents an alternative to oral agents for the acute phase of STEMI [111,114]. ...
Since the introduction of the first pharmacological therapy for the treatment of patients with acute myocardial infarction in the early 20th century, treatment of myocardial infarction has evolved extensively throughout the years. Mechanical revascularization therapies such as the percutaneous transluminal coronary angioplasty, combined with the ongoing development of pharmacological therapies have successfully improved the survival of patients with acute myocardial infarction. To date, antiplatelet therapy (consisting of aspirin and an oral P2Y12 inhibitor) and anticoagulation therapy represent the main stay of pharmacological treatment in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The routine use of clopidogrel as antiplatelet agent has been largely replaced by the use of the more potent P2Y12 inhibitors ticagrelor and prasugrel. Unfractionated heparin remains the preferred anticoagulant therapy, despite the development of other anticoagulants, including enoxaparin and bivalirudin. To date, limited evidence exists supporting a pre-hospital initiation of antiplatelet and anticoagulant therapy in STEMI patients. The use of potent intravenous antiplatelet agents, including the glycoprotein IIb/IIIa inhibitors and the intravenous P2Y12 inhibitor cangrelor, is currently restricted to specific clinical settings. While several potent antithrombotic agents already exist, the search for novel potent antithrombotic agents continues, with a focus on balancing antithrombotic properties with an improved safety profile to reduce excess bleeding. This review provides an overview of currently available pharmacological therapies for the treatment of STEMI patients undergoing primary PCI, and an outlook for the ongoing development of novel agents in this field.
... There was a reduction of acute and sub-acute ST in the pre-treatment group, despite the incidence of such events was overall very low (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days) [52]. It may be argued that the typically short time from diagnosis to coronary angiography (CA) in STEMI patients, the fact that patients with suspected STEMI may not present a type I MI but other conditions in which potent platelet inhibition is not beneficial (i.e., Takotsubo syndrome, pericarditis/myocarditis, aortic or coronary dissection, epicardial artery or microvascular spasm) and the increasing availability of intravenous antiplatelet agents such as cangrelor or glycoprotein IIb/IIIa inhibitors (GPIs) allowing for a bridging of platelet inhibition once coronary anatomy is known, filling the gap between oral P2Y 12 inhibitor administration and onset of action, makes the use routine use of P2Y 12 inhibitor pre-treatment more controversial [53][54][55]. Moreover, intravenous antiplatelet agents have the advantage of overcoming the reduced intestinal absorption of oral antiplatelet agents occurring during concomitant opioid administration [56]. ...
... Finally, in stable patients in whom the risk of thrombotic events is lower compared to ACS, the rationale as well as the evidence in support of P2Y 12 inhibitor pre-treatment is limited [32]. Cangrelor may represent a safe and effec-tive option for stable patients undergoing complex PCI [53]. Moreover, the use of intravenous aspirin in patients chronically treated with clopidogrel has been proposed as a simple but reasonable option to provide rapid and safe platelet inhibition by DAPT without increasing bleeding events [61]. ...
Percutaneous coronary intervention (PCI) is considered a relatively safe procedure associated with low rates of complications, but is inevitably associated with short and mid-to-long term increased bleeding risk. Besides the short term risk associated with the arterial access to perform PCI, enhanced bleeding risk persists for several months, given the need for antithrombotic therapy to prevent procedure-related thrombotic complications as well as ischemic recurrences. Bleeding is a powerful harbinger of adverse outcomes. This awareness has fuelled intense research on bleeding reduction strategies, including new PCI devices and techniques as well as new medications and antithrombotic regimens. We here review the mechanisms and prevalence of bleeding in PCI patients, discuss the available evidence from a practical point of view, and explore future perspectives on how to treat and prevent bleeding complications in these patients.
... И нгибиторы гликопротеина IIb / IIIa рецепторов тром боцитов (ИГ IIb / IIIa) -высокоэффективные парен теральные антитромбоцитарные препараты, блокирующие связывание фибриногена с активированными IIb / IIIa рецеп торами -реакцию, обеспечивающую «склеивание» тромбо цитов при образовании агрегатов [1]. ИГ IIb / IIIa в течение длительного времени назначались при чрескожных коронар ных вмешательствах (ЧКВ) у больных с острым коронар ным синдромом (ОКС). ...
... Эптифибатид и тирофибан конкурентно блокируют рецепторы IIb / IIIa за счет содержания последовательно стей аминокислот, аналогичных гаммацепи и альфацепи фибриногена [2]. Эптифибатид представляет собой ци клический синтетический гептапептид, содержащий це почку аминокислот с KGDпоследовательностью, подоб ной последовательности барбурина -белка яда гремучих змей [1,9]. Тирофибан является синтетическим пептидо миметиком, его молекула не содержит пептидных связей, но ее структура, созданная на основе тирозина, сходна с RGDаминокислотной последовательностью [10]. ...
... Тирофибан является синтетическим пептидо миметиком, его молекула не содержит пептидных связей, но ее структура, созданная на основе тирозина, сходна с RGDаминокислотной последовательностью [10]. Мо лекулярная масса конкурентных ИГ IIb / IIIa менее 1 кДа, поэтому их называют «малыми молекулами» [1]. ...
Current management of patients with acute coronary syndrome (ACS) includes a dual antiplatelet therapy with acetylsalicylic acid and a platelet P2Y12 receptor inhibitor. For patients without a high risk of bleeding, prasugrel and ticagrelor are preferred, since their effect is more pronounced, less dependent on metabolism of a specific patient, and occurs faster that the effect of clopidogrel. The prescription rate of platelet glycoprotein IIb/IIIa (GP IIb / IIIa) receptor inhibitors has considerably decreased. However, these drugs remain relevant in percutaneous coronary interventions in patients with a high risk of coronary thrombosis or a massive coronary thrombus, in thrombotic complications of the procedure, and in the “no-reflow” phenomenon. The intravenous route of GP IIb / IIIa inhibitor administration provides their effectiveness in patients with difficulties of drug intake or with impaired absorption of oral medications. This review presents clinical and pharmacological characteristics of various GP IIb / IIIa inhibitors and data of randomized clinical studies and registries of recent years that evaluated results of their use in patients with ACS.
... Importantly, peri-PCI thrombotic complications impact long-term prognosis, to the extent that their occurrence has challenged the long-term clinical benefit of PCI as compared to medical therapy among patients with CCS 22,23 . Intravenous antiplatelet agents, including glycoprotein IIb/IIIa inhibitors (GPIs) and cangrelor, reduce the risk of peri-PCI thrombotic complications 24 . A detailed description of intravenous antiplatelet agents goes beyond the scope of this manuscript and is summarised elsewhere 24 . ...
... Intravenous antiplatelet agents, including glycoprotein IIb/IIIa inhibitors (GPIs) and cangrelor, reduce the risk of peri-PCI thrombotic complications 24 . A detailed description of intravenous antiplatelet agents goes beyond the scope of this manuscript and is summarised elsewhere 24 . ...
Antiplatelet therapy is key to reducing local thrombotic complications and systemic ischaemic events among patients undergoing percutaneous coronary interventions (PCI), but it is inevitably associated with increased bleeding. The continuous refinement in stent technologies, together with the high incidence of ischaemic recurrences after PCI and the understanding of prognostic implications associated with bleeding, have led to a substantial evolution in antiplatelet treatment regimens over the past decades. Numerous investigations have been conducted to better stratify patients undergoing PCI according to their ischaemic and bleeding risks and to implement antithrombotic regimens accordingly. Evidence from these investigations have resulted in a number of antithrombotic treatment options as recommended by recent guidelines. In this State-of-the-Art review we provide the rationale, summarise the evidence, and discuss current and future directions of antiplatelet treatment regimens after PCI.
... Administered intravenously, cangrelor has an ultra-short half-life of 3-6 min and rapid onset and offset effects allowing a rapid recovery of platelet function within 1 h [68]. The recommended dosage of cangrelor in ACS patients is 30 µg/kg IV bolus (administered in less than 1 min), followed immediately by a 4 µg/kg/min IV infusion for at least 2 h or the duration of percutaneous coronary intervention (PCI) [69,70]. It is an interesting therapeutic option in ACS patients not pre-treated with an oral P2Y 12 receptor antagonist who need urgent PCI [71] or those who require DAPT bridging before surgery [72]. ...
... Eptifibatide is administered as a bolus of 180 µg/kg (with another 180 µg/kg later if PCI is performed) and an infusion of 2 µg/kg/min (for 18 h), and tirofiban is administered as a bolus of 25 µg/kg (over 3 min.) followed by an infusion of 0.15 µg/kg/min (up to 18 h) [69]. Their half-lives are 2.5 and 2 h and the time to steady-state platelet inhibition is ≤15 min and 20-40 min, respectively. ...
Over the last decades, antiplatelet agents, mainly aspirin and P2Y12 receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy and safety in various clinical settings have established antithrombotic efficacy. Notwithstanding, antiplatelet agents carry an inherent risk of bleeding. Given that bleeding is associated with adverse cardiovascular outcomes and mortality, there is an unmet clinical need to develop novel antiplatelet therapies that inhibit thrombosis while maintaining hemostasis. In this review, we present the currently available antiplatelet agents, with a particular focus on their targets, pharmacological characteristics, and patterns of use. We will further discuss the novel antiplatelet therapies in the pipeline, with the goal of improved clinical outcomes among patients with atherothrombotic diseases.
