Abciximab as an adjunctive therapy for patients undergoing percutaneous coronary interventions

Introduction: Platelets play a central role in the pathophysiology of acute coronary syndromes (ACS) and activation of platelet glycoprotein (GP) IIb/IIIa receptor is critical to platelet aggregation. Abciximab, a human murine chimeric antibody to the GPIIb/IIIa receptor, is an important biological therapy in the management of patients presenting with ACS.

Areas covered: The objective of this review is to define the role of abciximab in the management of ACS by interpreting the available data from randomized clinical trials using abciximab in various clinical scenarios, particularly in percutaneous coronary intervention (PCI). We also review different modes of delivery and describe the adverse effects of abciximab including thrombocytopenia. Where possible, we attempt to compare abciximab to the other available GPIIb/IIIa inhibitors. We hope the reader will gain a better understanding of the benefits and risks of abciximab and the important role it has in the management of cardiology patients.

Expert opinion: Abciximab was a breakthrough drug in the management of high risk ACS patients undergoing PCI. However, with newer available therapies and improvement in PCI technology, dose and delivery of this drug have evolved as we try to extract maximum benefit while minimizing the adverse effects associated with it.     

Glycoprotein IIb/IIIa receptor inhibitors in percutaneous coronary intervention and acute coronary syndrome

OBJECTIVE: To review the contemporary role of the glycoprotein (GYP) IIb/IIIa receptor inhibitors abciximab, eptifibatide, and tirofiban in patients undergoing percutaneous coronary intervention (PCI) and those with an acute coronary syndrome (ACS), and to provide an algorithm based on currently available evidence for specific agents. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966-January 2003); references cited in these articles provided additional resources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from data sources were considered for relevant information; this article primarily addresses large, controlled or comparative studies, and meta-analyses. DATA SYNTHESIS: The role of GYP IIb/IIIa inhibitors in patients undergoing PCI and those with ACS has progressed markedly. To date, abciximab has the most robust data in patients undergoing PCI, particularly high-risk individuals. In PCI patients with lower risk (e.g., elective stenting), eptifibatide is a reasonable first-line option. Data do not support tirofiban for routine use in patients undergoing PCI. For individuals with signs and symptoms of ACS, specifically unstable angina or non-ST-segment elevation myocardial infarction (MI), eptifibatide or tirofiban is recommended in high-risk patients when a conservative approach is used (PCI is not planned). Abciximab is not recommended in this situation. In patients with ST-segment elevation MI (STEMI), abciximab is the only GYP IIb/IIIa inhibitor evaluated in large, well-designed investigations. For medical management in combination with a fibrinolytic agent, the role of abciximab remains unclear. For patients undergoing primary PCI for the management of STEMI, the available evidence supports the use of abciximab, albeit further investigation is warranted. CONCLUSIONS: The role of GYP IIb/IIIa inhibitors in clinical cardiology continues to evolve. Choice of the agent depends on situation of use, patient-specific characteristics and risk stratification, and, in the case of ACS, chosen management strategy (medical management or intervention).     

Abciximab and atherosclerotic heart disease: use in percutaneous coronary intervention,acute coronary syndromes and acute myocardial infarction

Abciximab irreversibly binds to the glycoprotein IIb/IIIa receptor on both activated and unactivated platelets inhibiting platelet aggregation. It has been studied in a variety of clinical settings including percutaneous coronary intervention (PCI), ST-elevation myocardial infarction, and non ST-elevation acute coronary syndromes. Abciximab has been demonstrated to reduce acute ischaemic events in the setting of percutaneous intervention with both percutaneous transluminal coronary angioplasy and stenting. It has been shown to be particularly effective when used in patients with acute myocardial infarction undergoing primary PCI. The data for its effective use in the medical phase of therapy for patients with acute coronary syndromes, however, is not as consistent. In this article we review the major trials evaluating the use of abciximab in these clinical scenarios compared with placebo and alternative glycoprotein IIb/IIIa inhibitors.     

The evolving role of platelet glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndromes.

OBJECTIVE: To briefly discuss the pathophysiology of acute coronary syndromes (ACS) and to present the clinical data currently available regarding the use of platelet glycoprotein (GP) IIb/IIIa inhibitors in the management of ACS. DATA SOURCES: Literature on antithrombotic therapy in ACS was identified using a MEDLINE search (January 1988-September 1998), along with the Agency on Health Care Policy and Research guidelines for the management of unstable angina. Abstracts from recent scientific meetings were also reviewed. STUDY SELECTION: Review articles from the cardiology literature (pathophysiology) and randomized, controlled clinical trials of currently approved platelet GP IIb/IIIa inhibitors in ACS were evaluated. Ex vivo platelet aggregation studies and pharmacology literature were also included. Abstract data were included to illustrate specific points when published literature was not available. DATA EXTRACTION: Study data were evaluated based on study design, outcome parameters, and adverse drug reactions. Clinical information from review articles was evaluated based on applicability to the treatment of ACS. DATA SYNTHESIS: Platelet adhesion and aggregation are pivotal events in the pathophysiology of ACS. The GP IIb/IIIa inhibitors represent a new and unique class of drugs that block fibrinogen and von Willebrand factor-mediated platelet aggregation, the common end point of all biologic pathways of platelet aggregation. Three agents are currently approved by the Food and Drug Administration: abciximab, a monoclonal antibody; eptifibatide, a synthetic peptide; and tirofiban, a synthetic nonpeptide. CONCLUSIONS: Clinical trial data demonstrate efficacy of all three GP IIb/IIIa inhibitors in reducing the combined end point of morbidity and mortality in patients undergoing angioplasty. Eptifibatide and tirofiban also reduce the combined end point of morbidity and mortality in patients with unstable angina. These data expand the present role of platelet GP IIb/IIIa inhibitors by providing evidence for their effectiveness in the medical treatment of ACS. However, the specific role that these agents will have in the management of ACS is yet to be fully defined.     

Occupancy of the internal and external pools of glycoprotein IIb/IIIa following abciximab bolus and infusion

The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the occupancy of the internal and external pools of GPIIb/IIIa and platelet function following an abciximab bolus and infusion, 15 patients undergoing elective percutaneous transluminal coronary angioplasty were administered abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and TRAP-6 (20 microM)-activated samples (to expose the internal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhibition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupancy (range 82--99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 microM ADP (maximal, 11 +/- 2% of baseline), but less so to 5 microM TRAP-6 (maximal, 36 +/- 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappearance of abciximab from the platelet surface. Maximum inhibition of platelet function and receptor occupancy of the external pool of GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some internal receptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.     

STEER-IT ™ deflecting tip guidewire available in USA,Canada and Europe

The glycoprotein (GP) IIb/IIIa receptor serves as the final common pathway of platelet-thrombus formation. Thus, the GP IIb/IIIa receptor has been identified as a target for the prevention of thrombus formation during acute coronary syndromes and/or percutaneous coronary intervention. While there are several intravenous GP IIb/IIIa inhibitors available, abciximab has proven to be a dependable agent with unique properties. Based on American College of Cardiology, American Heart Association and Society for Angiography and Interventions guidelines, compared with the other available intravenous GP IIb/IIIa inhibitors, abciximab receives the highest recommendation for use in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Abciximab is also unique in that there is no need for renal dosing and its effects are mostly reversible with platelet transfusions.     

Abciximab: a review and update for clinicians

The glycoprotein (GP) IIb/IIIa receptor serves as the final common pathway of platelet-thrombus formation. Thus, the GP IIb/IIIa receptor has been identified as a target for the prevention of thrombus formation during acute coronary syndromes and/or percutaneous coronary intervention. While there are several intravenous GP IIb/IIIa inhibitors available, abciximab has proven to be a dependable agent with unique properties. Based on American College of Cardiology, American Heart Association and Society for Angiography and Interventions guidelines, compared with the other available intravenous GP IIb/IIIa inhibitors, abciximab receives the highest recommendation for use in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Abciximab is also unique in that there is no need for renal dosing and its effects are mostly reversible with platelet transfusions.     

Concentration-dependent effect of abciximab on platelets and neutrophils in a model of cardiopulmonary bypass

Abciximab is a GPIIb/IIIa antagonist used in percutaneous coronary interventions to avoid platelet activation, thrombosis and inflammation. We investigated whether abciximab influenced platelet activation and platelet interaction with neutrophils and polyvinyl chloride (PVC) in a cardiopulmonary bypass (CPB) model. Isolated platelets, preincubated with and without 0.1-20 microg/mL of abciximab, were resuspended with neutrophils in plasma and recirculated by a roller pump. Platelet, but not neutrophil adhesion to PVC was inhibited by abciximab. Only high doses of abciximab reduced platelet aggregation size, but simultaneously increased platelet-neutrophil aggregation. Abciximab had no effect on platelet CD62P expression or degranulation, but platelet activation on platelet-neutrophil aggregates increased with high doses. Only low doses inhibited neutrophil degranulation. The concentration-dependent effect of abciximab on platelet-neutrophil interaction reduces its usefulness and stresses the dependency on experimental design in the evaluation of abciximab. Our study does not support the use of abciximab alone in CPB. However, incorporation of surface-coating the biomaterial with abciximab may be an interesting option.     

Pharmacodynamics of abciximab during angioplasty: comparison to healthy subjects

OBJECTIVES: Our objectives were to compare and contrast abciximab concentration-effect relationships in healthy volunteer participants with those in patients with coronary atherosclerosis undergoing elective coronary angioplasty. We also aimed to establish abciximab plasma concentrations associated with 80% inhibition of platelet aggregation. METHODS: Abciximab clearance and concentration-effect relationships were determined from two separate clinical studies, one in 30 healthy subjects aged 21 to 66 years and the other in 32 patients aged 44 to 74 years before they underwent elective coronary angioplasty. After abciximab administration, abciximab plasma concentrations, platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor occupancy, and degree of inhibition of platelet aggregation in the presence of 5-micromol/L and 20-micromol/L adenosine diphosphate was determined. With an E(max) (receptor occupancy) or inhibitory E(max) (inhibition of platelet aggregation) model, abciximab concentrations required for 80% receptor occupancy and 80% inhibition of platelet aggregation were determined. RESULTS: Abciximab steady-state clearance in healthy participants was 183 +/- 72 ml/min (mean +/- SD), and single-dose clearance in patients undergoing angioplasty was 405 +/- 240 ml/min (mean +/- SD). Abciximab concentration required for 80% GP IIb/IIIa receptor occupancy was 35.2 +/- 2.4 versus 72.8 +/- 6.4 ng/ml in healthy participants versus patients (P <.01). Concentrations required for 80% inhibition of platelet aggregation stimulated by 5-micromol/L adenosine diphosphate were 25.6 +/- 1.6 versus 68.9 +/- 9.2 ng/ml (P <.01). Similarly, the concentrations required for 80% inhibition of platelet aggregation stimulated by 20-micromol/L adenosine diphosphate were 56.0 +/- 3.2 versus 141 +/- 16.8 ng/ml (P <.01). CONCLUSION: Approximately 2-fold greater abciximab exposure is required to achieve the same degree of GP IIb/IIIa occupancy and inhibition of platelet aggregation in patients undergoing angioplasty as compared with healthy participants. The difference between groups may be related either to different states of basal platelet activation or to the effect of heparin that patients received as part of the angioplasty procedure. A therapeutic concentration range for patients is 100 to 175 ng/ml, because this is the concentration consistent with >80% inhibition of platelet aggregation when 20-micromol/L adenosine diphosphate is used as the aggregating stimulus.     

Platelet glycoprotein IIb/IIIa-receptor inhibitors in patients with acute coronary syndromes or undergoing percutaneous coronary interventions: a review

BACKGROUND: Over 12.2 million Americans are affected by acute coronary syndromes (ACS) resulting from arterial thrombosis after atherosclerotic plaque rupture. The mechanism of thrombosis is based on the platelet activation pathway, facilitated by expression of the platelet glycoprotein (GP) lIb/Illa receptors. The platelet GP IIb/IIIa-receptor inhibitors represent a new class of drugs, of which abciximab, eptifibatide, and tirofiban have been approved for use in the medical management of ACS and as adjunctive therapy in percutaneous coronary interventions (PCIs). OBJECTIVE: This article reviews the results of published multicenter, randomized, placebo-controlled, double-blind trials of the efficacy and safety of platelet GP IIb/IIIa-receptor inhibitors in patients with coronary artery disease. METHODS: To identify articles for this review, a search of MEDLINE for the years 1994 through 2000 was conducted using the key words myocardial ischemia, unstable angina, angioplasty, stent, abciximab, eptifibatide, tirofiban, lamifiban, and platelet aggregation inhibitors. Relevant review articles were consulted as well as reports of clinical studies. CONCLUSIONS: Three GP IIb/IIIa-receptor inhibitors--abciximab, eptifibatide, and tirofiban-are approved by the US Food and Drug Administration as adjunctive therapy in patients undergoing PCI. Eptifibatide and tirofiban 'are also indicated for the medical management of patients with unstable angina and non-ST-segment-elevation myocardial infarction. The use of GP IIb/IIIa-receptor inhibitors as a component of management with fibrinolytic agents is under investigation. Studies comparing the efficacy of tirofiban and abciximab in patients undergoing planned PCI with intracoronary stent placement are in progress. Until data are available from long-term trials and head-to-head comparisons of these agents, it is not possible to generalize about their overall or comparative efficacy.     

Present and evolving role of eptifibatide in the treatment of acute coronary syndromes

Platelet-dependent thrombosis plays a central role in the pathophysiology of myonecrosis in both percutaneous coronary interventions (PCIs) and acute coronary syndromes (ACS). Extensive data from randomized clinical trials support the use of acute therapies that interfere with platelet aggregation to provide clinical benefit to patients presenting with ACS and undergoing PCI. Glycoprotein (GP) IIb/IIIa receptor antagonists represent a major advance in the therapy of patients undergoing PCI and those with non-ST segment elevation (NSTE) ACS. Eptifibatide, a small molecule GP IIb/IIIa receptor antagonist, is one such agent. A more consistent platelet-inhibitory effect over time and the short half-life of eptifibatide represent potential pharmacologic advantages compared with other drugs within this class. Large, randomized clinical trials have demonstrated the benefits of eptifibatide for treating patients with NSTE ACS and patients undergoing PCI, establishing its central role in modern management of these conditions. However, recent new advances in the pharmacotherapy of ACS and PCI are requiring us to reconsider the role of GP IIb/IIIa inhibitors; therefore, ongoing and future randomized clinical trials will re-examine GP IIb/IIIa inhibition and establish the role of GP IIb/IIIa inhibitors for the next decade.     

Eptifibatide vs abciximab as adjunctive therapy during primary percutaneous coronary intervention for acute myocardial infarction

OBJECTIVE: To compare outcomes among patients receiving eptifibatide or abciximab during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) with ST elevation or new left bundle branch block. PATIENTS AND METHODS: From January 1999 through January 2004, 576 patients underwent primary PCI and received adjunctive glycoprotein IIb/IIIa receptor antagonists. Propensity scores were used to adjust for baseline differences between groups. Logistic regression and Cox proportional hazards were used to model the association between choice of glycoprotein IIlb/IIIa receptor antagonist and adverse events. RESULTS: Abciximab was given to 327 patients (57%) and eptifibatide to 249 (43%). Observed rates of in-hospital death or MI did not differ between groups (eptifibatide, 6%; abciximab, 5%; P = .95). This result persisted with adjustment for various patient characteristics (adjusted odds ratio, 1.03; 95% confidence interval, 0.40-2.65; P = .95). Kaplan-Meier estimated rates of death, MI, or target vessel revascularization at 1-year follow-up were 20.9% with eptifibatide and 22.3% with abciximab. The adjusted hazard ratio for the composite end point during a median follow-up of 12 months was 1.36 (95% confidence interval, 0.89-2.07; P = -.16). CONCLUSION: In this observational analysis, outcomes were similar with use of either abciximab or eptifibatide among patients undergoing primary PCI for acute MI. Additional comparative research is warranted to confirm these results.     

Therapeutics of platelet glycoprotein IIb/IIIa receptor antagonism

The integrin glycoprotein IIb/IIIa receptor is the final common pathway to platelet aggregation. Administration of glycoprotein IIb/IIIa receptor antagonists reduces acute ischemic complications following plaque fissuring or rupture. Research on this subject was initially limited to patients undergoing percutaneous coronary intervention. Further studies evaluating the role of glycoprotein IIb/IIIa receptor antagonists in patients with non-ST segment elevation acute coronary syndrome have shown benefit of these drugs in reducing adverse cardiac events and death. Intravenous glycoprotein IIb/IIIa receptor inhibitors (abciximab, tirofiban, and eptifibatide) given in combination with traditional regimens are superior to placebo in management of non-ST elevation acute myocardial infarction. Oral glycoprotein IIb/IIIa receptor inhibitors (orbofiban, sibrafiban, and xemilofiban) are not effective in reducing ischemic events when used on a long-term basis after acute coronary syndrome. Pharmacokinetics, efficacy, and safety of glycoprotein IIb/IIIa receptor antagonists are elaborated.     

Role of abciximab in the treatment of coronary artery disease

Glycoprotein IIb/IIIa complex is a crucial membrane receptor for platelet aggregation, binding platelets to fibrinogen and establishing interplatelet bridges. This receptor is the common end point of the multiple activation pathways of a platelet. Antiplatelet agents, such as aspirin or thienopyridines, including ticlopidine and clopidogrel, inhibit one or more but not all, of these pathways. Inhibitors of the receptor are powerful platelet antiaggregants and include two groups of agents: non-competitive receptor blockers, such as abciximab, and competitive antagonists, such as tirofiban and eptifibatide. Abciximab is a monoclonal antibody that binds to the glycoprotein IIb/IIIa complex, thus blocking the interaction with fibrinogen. It is used for treatment of coronary artery disease, being well-studied in the setting of acute coronary syndromes and percutaneous coronary intervention, in which a rapid and effective antiaggregation is clinically important.     

Role of abciximab in the treatment of coronary artery disease

Glycoprotein IIb/IIIa complex is a crucial membrane receptor for platelet aggregation, binding platelets to fibrinogen and establishing interplatelet bridges. This receptor is the common end point of the multiple activation pathways of a platelet. Antiplatelet agents, such as aspirin or thienopyridines, including ticlopidine and clopidogrel, inhibit one or more but not all, of these pathways. Inhibitors of the receptor are powerful platelet antiaggregants and include two groups of agents: non-competitive receptor blockers, such as abciximab, and competitive antagonists, such as tirofiban and eptifibatide. Abciximab is a monoclonal antibody that binds to the glycoprotein IIb/IIIa complex, thus blocking the interaction with fibrinogen. It is used for treatment of coronary artery disease, being well-studied in the setting of acute coronary syndromes and percutaneous coronary intervention, in which a rapid and effective antiaggregation is clinically important.     

Role of low-molecular-weight heparin in invasive management of non-ST-elevation acute coronary syndromes

OBJECTIVE: To review the available literature addressing the role of low-molecular-weight heparin (LMWH) as an alternative to unfractionated heparin (UFH) in percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndromes (NSTEACS). DATA SOURCES: A MEDLINE search (1966-March 2004) identified pertinent articles using the key words acute coronary syndromes, unstable angina, non-ST-elevation myocardial infarction, low-molecular-weight heparin, enoxaparin, dalteparin, glycoprotein IIb/IIIa receptor antagonists, abciximab, tirofiban, eptifibatide, percutaneous transluminal coronary angioplasty, and percutaneous coronary intervention. The references of these articles were reviewed for additional pertinent references. STUDY SELECTION AND DATA EXTRACTION: All human trials of LMWH in PCI for treatment of NSTEACS were evaluated. All pertinent studies were included in the review. DATA SYNTHESIS: Administration of LMWH with or without a glycoprotein IIb/IIIa inhibitor during PCI appears to be similar to UFH in terms of efficacy. LMWH, especially in combination with a glycoprotein IIb/IIIa inhibitor, may increase risk of bleeding compared with UFH. CONCLUSIONS: Available clinical trials do not provide definitive evidence to suggest superiority of LMWH over UFH when managing NSTEACS during PCI; however, dosing strategies are available if an LMWH is to be used in this setting.     

Dissolution of thrombus formed during direct coronary angioplasty with a single 10 mg intracoronary bolus dose of abciximab

Direct coronary angioplasty with stent implantation is an effective treatment for acute myocardial infarction. The use of adjunctive abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist is expensive. We report on three cases of direct coronary angioplasty complicated by extensive thrombus formation that were successfully treated with attenuated dosing of abciximab via the intracoronary route. All patients presented with acute myocardial infarction complicated by cardiogenic shock or eminent cardiogenic shock. Abciximab was administered after balloon dilatation when extensive thrombus formation was noted and persisted despite repeated inflations. In all three patients a single 10 mg vial of intracoronary abciximab was administered, resulting in complete dissolution of thrombus, allowing successful deployment of stents. Thus, a single 10 mg intracoronary bolus dose of abciximab may be sufficient to achieve high local concentrations of antiplatelet activity. This facilitates thrombus dissolution and allows the safe deployment of a stent to normalise intracoronary rheology.     

Assessment of the bioequivalence of brand and biogeneric formulations of abciximab for the treatment of acute coronary syndrome: A prospective,open-label,randomized, controlled study in Korean patients

Background: Abciximab has been found to reduce major adverse cardiovascular events in patients with acute coronary syndrome (ACS). A previous study reported on the tolerability of biogeneric abciximab in patients with ACS. This formulation has been approved by the Korea Food and Drug Administration and is currently being marketed. Its ex vivo antiplate-let effect, however, has not been compared with that of branded abciximab.Objective: The purpose of the present study was to compare ex vivo antiplatelet activity, angiographic outcome, and bleeding complications between biogeneric and branded abciximab.Methods: This prospective, open-label, randomized, controlled study was conducted in Korea. Patients with ACS who underwent percutaneous coronary intervention (PCI) were randomized to receive bioge-neric abciximab or branded abciximab. All patients received intracoronary unfractionated heparin 70 IU/kg and either biogeneric or branded abciximab 0.25 mg/kg IV bolus ~10 minutes before undergoing PCI, followed by a 0.125 μg/kg/min 12-hour infusion of the same formulation. The antiplatelet effect of both drugs was assessed at 3 time points (at baseline, and 10 minutes and 24 hours after the end of the bolus infusion) using a validated rapid platelet-function assay.Results: In total, 37 patients (30 men and 7 women; 19 receiving biogeneric abciximab and 18 receiving branded abciximab) were included. Patient demographics did not differ significantly between the 2 groups (16 men [84.2%] and 3 women [15.8%] in the biogeneric group vs 14 men [77.8%] and 4 women [22.2%] in the branded group; mean [SD] age, 65 [11] vs 60 [10] years; weight, 64.6 [8.7] vs 67.9 [10.1] kg, respectively). The bolus and the continuous infusion of the biogeneric and branded formulations achieved similar levels of platelet inhibition, with a mean (SD) inhibition of platelet aggregation >90% at 10 minutes after the end of the bolus infusion (94.7% [8.2%] vs 92.6% [16.9%], respectively; P = NS) and >65% at 24 hours (68.1% [9.8%] vs 70.9% [9.7%]; P = NS) compared with baseline. One thrombolysis in myocardial infarction major bleeding complication (retro-peritoneal hemorrhage) was reported in a patient who received biogeneric abciximab.Conclusion: There were no statistically significant differences in the antiplatelet effects of these 2 formulations in this small, selected population of Korean patients with ACS.     

Troponin level and efficacy of abciximab in patients with acute coronary syndromes undergoing early intervention after clopidogrel pretreatment

Objective We investigated how does troponin level (TnT) affect the benefit achieved by abciximab in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with a high loading dose of clopidogrel. Methods The Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) trial included 2,022 patients with non-ST elevation ACS undergoing PCI who were randomized to abciximab or placebo after pretreatment with 600 mg of clopidogrel. The patients were divided into groups with elevated TnT level (n = 1,049) and no elevated TnT level (n = 973). The primary end point of the trial was the composite of death, myocardial infarction and urgent reintervention at 30 days. Results In patients with elevated TnT level the incidence of the primary end point was 13.1% in the abciximab group Vs. 18.3% in the placebo group [relative risk (RR): 0.70; 95% confidence interval (CI), 0.52–0.95, P = 0.02]. The combined incidence of death or myocardial infarction was 12.9% in the abciximab group vs. 17.9% in the placebo group (RR: 0.71; 95% CI, 0.52–0.96, P = 0.03). In contrast, the incidence of the primary end point in patients with no elevated TnT level was identical in both treatment groups (4.6%). The risk of bleeding was not related to TnT level. Conclusions Baseline troponin level affects the benefit of abciximab in patients with ACS undergoing PCI after pretreatment with a high loading dose of clopidogrel. Abciximab reduces the risk of ischemic events only in patients with ACS and elevated troponin level.     

Variability of platelet aggregate dispersal with glycoprotein IIb–IIIa antagonists eptifibatide and abciximab

Summary.  Background:  Utilization of glycoprotein IIb–IIIa (GPIIb–IIIa) inhibitors improves outcomes of patients with acute coronary syndromes (ACS), including those undergoing percutaneous coronary intervention (PCI). These results may be related to the ability of the inhibitors to destabilize coronary thrombi, reduce microembolization, and restore vessel patency. Objective:  To evaluate in vitro the ability of GPIIb–IIIa antagonists, abciximab and eptifibatide, to promote the disaggregation of platelet-rich thrombus. Methods: Antagonist-induced disaggregation was assayed in plasma by aggregometry, as well as in whole blood by point of care and capillary perfusion systems. Fibrinogen dissociation from the platelet surface was quantified by flow cytometry. Results:  Significant disaggregation of 5 μ m ADP-induced aggregates was observed after addition of either agent. The maximum extent and rate of disaggregation were significantly higher with eptifibatide than with abciximab. Both antagonists also dispersed 2 μg mL⁻¹ collagen-induced aggregates, again with eptifibatide having a greater effect. Eptifibatide, but not abciximab (up to 10 μg mL⁻¹), was efficient at dissociating aggregates to single platelets in whole blood and dispersing aggregates that had been aged for 30 min before treatment. Eptifibatide also reduced existing thrombus burden in the perfusion model under arterial flow conditions. A key mechanism of aggregate dispersal was antagonist-induced displacement of platelet-bound fibrinogen, which was greater with eptifibatide, a competitive inhibitor of fibrinogen binding, than with the noncompetitive inhibitor, abciximab. Conclusions:  These results suggest that drug concentration and residence time, along with thrombus extent and age, may be critical determinants in promoting timely recanalization.