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.     

Evaluation of bleeding complications associated with glycoprotein IIb/IIIa inhibitors

BACKGROUND: Platelet glycoprotein IIb/IIIa inhibitors are used with aspirin and heparin to decrease rates of death, myocardial infarction, and urgent revascularization in patients with acute coronary syndromes. OBJECTIVE: To determine whether bleeding event rates differed among 3 glycoprotein IIb/IIIa inhibitors prescribed in a high-risk, elderly veteran population and identify risk factors for bleeding. METHODS: A retrospective chart analysis of patients who received abciximab, eptifibatide, or tirofiban was conducted. chi(2) Analysis evaluated the incidence of bleeding complications, and stepwise regression analysis was utilized to identify bleeding risk factors. Parameters evaluated as possible risk factors for bleeding included age, renal function, weight, heparin and glycoprotein IIb/IIIa inhibitor dosing and infusion duration, concomitant antiplatelet and/or anticoagulant medications or disease states, and baseline hemoglobin, hematocrit, or platelet counts. RESULTS: Of 348 patients whose charts were reviewed, 79 patients were included. There were 37.9% who received abciximab (n = 30), 30.3% who received eptifibatide (n = 24), and 31.6% who received tirofiban (n = 25). Twenty-one bleeding events not related to coronary artery bypass grafting occurred: only 1 major bleed (tirofiban) and 20 minor bleeds. Bleeding rates were not significantly different between groups: abciximab 30% (n = 9), eptifibatide 21% (n = 5), and tirofiban 28% (n = 7). Significant risk factors for bleeding included patient weight, infusion duration, and baseline platelet count (p = 0.024). Patients who bled received significantly more transfusions of packed red blood cells and platelets than patients with no bleeding (p = 0.047). CONCLUSIONS: Although bleeding complications did not differ significantly between the 3 drugs, several risk factors for bleeding events were identified. A considerable rate of bleeding events occurred in this high-risk patient population.     

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.     

Effect of abciximab on the outcome of emergency coronary artery bypass grafting after failed percutaneous coronary intervention

OBJECTIVE: To evaluate the outcome of coronary artery bypass grafting (CABG) for failed percutaneous coronary intervention (PCI) in patients who had received abciximab. PATIENTS AND METHODS: In this retrospective study, we analyzed the records of patients who had PCI at our institution between January 1994 and December 1998 and identified those who had urgent or emergency CABG within 48 hours after PCI. CABG was performed for failed PCI in patients who had ongoing ischemia, hemodynamic compromise, or both. These patients were categorized into 2 groups depending on whether they had been given abciximab during PCI. We compared blood product transfusion requirements, bleeding complications, and frequency of in-hospital adverse events of the 2 groups. RESULTS: Of 5636 patients who had PCI, 77 (1.4%) had urgent or emergency CABG within 48 hours, including 11 who were given abciximab (abciximab group) during PCI and 66 who were not given abciximab (no abciximab group). The 2 groups had similar baseline characteristics. The mean +/- SD time to surgery was 8.4 +/-8.0 hours (median, 6 hours) for the abciximab group vs 12.1 +/- 12.5 hours (median, 4 hours) for the no abciximab group. Major bleeding (Thrombolysis in Myocardial Infarction criteria) occurred in 9 (90%) of 10 patients in the abciximab group vs 48 (77%) of 62 patients in the no abciximab group. The total volumes of intraoperative autotransfusion and transfusion of red blood cells and fresh frozen plasma tended to be higher for the abciximab group. Also, this group received a mean of 13.9 U of platelets vs 3.2 U for the no abciximab group (P<.001). However, no in-hospital deaths occurred among patients in the abciximab group, and adverse events were infrequent and comparable between the 2 groups. No difference was noted between the 2 groups in the frequency of surgical reexploration for bleeding. CONCLUSION: Transfusion requirements are higher for patients who undergo emergency or urgent CABG after having received abciximab during PCI. However, in-hospital adverse events are infrequent and comparable to those for patients who do not receive abciximab.     

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.     

Pulmonary hemorrhage after percutaneous coronary intervention with abciximab therapy

Abciximab has a key role in the treatment of patients with acute coronary syndromes undergoing percutaneous coronary intervention; however, an increased risk of bleeding complications is well recognized. We report a case of serious pulmonary hemorrhage after use of abciximab therapy. A definitive indication and treatment guideline should be available to minimize serious bleeding complications. Additionally, respiratory symptoms should be monitored closely for early detection of serious pulmonary hemorrhage in patients receiving abciximab therapy during percutaneous coronary intervention.     

Prehospital treatment of patients with acute myocardial infarction with bivalirudin

Objectives

Patients with acute myocardial infarction are at high risk of dying within the first hours after onset of coronary ischemia. Therefore, pharmacological intervention should be started in the prehospital setting. This study investigates the effect of the prehospital administration of bivalirudin on short-term morbidity and mortality compared to heparin plus abciximab in patients with ST-segment-elevation myocardial infarction (STEMI).

Methods

One hundred ninety-eight patients with STEMI treated with bivalirudin in the prehospital setting were prospectively collected. Coronary angiography was performed to identify the infarct-related artery. In case of a percutaneous coronary intervention, bivalirudin was given according to the guidelines. The historic control group consisted of 171 consecutive patients from the same myocardial infarction network treated with unfractioned heparin and abciximab administration before the admission to the emergency department of the percutaneous coronary intervention center. The primary outcome parameter was the incidence of major adverse cardiac events (recurrent myocardial infarction, stroke, death, target vessel revascularization for ischemia) within 30 days after the primary event.

Results

The overall rate of major adverse cardiac events was significantly lower in the bivalirudin group compared to the abciximab group (7.6% vs 14.6%; P = .04). The number of major bleedings was significantly higher in the abciximab group compared to the bivalirudin group (11.8% vs 3.8%; P = .03).

Conclusions

The use of bivalirudin in the prehospital setting leads to a reduced rate of major cardiovascular events compared to a standard treatment with abciximab plus heparin. Bivalirudin is a reasonable choice of treatment in the prehospital setting for patients with STEMI.     

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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.     

Outcomes and costs of abciximab versus eptifibatide for percutaneous coronary intervention

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) with stent placement are often prescribed glycoprotein IIb/IIIa inhibitors. However, drug selection is often based on clinicians' preference and cost because few studies have directly compared abciximab and eptifibatide. OBJECTIVE: To compare clinical outcomes and total hospital costs of abciximab and eptifibatide in patients undergoing stent placement during PCI in a real-world setting. METHODS: A retrospective cohort analysis was conducted of 960 patients administered abciximab or eptifibatide for intracoronary stent placement between 1999 and 2001 at a tertiary care hospital. The primary outcome was bleeding, defined as major, moderate, or minor according to published criteria. Secondary outcomes included in-hospital death, myocardial infarction, revascularization, and the triple composite endpoint of those outcomes, thrombocytopenia, length-of-stay, and total hospital costs. Pearson's chi(2) analysis, Fisher's exact test, and ANOVA were used for statistical analysis. RESULTS: The frequency of bleeding complications based on severity was similar between abciximab and eptifibatide: major (2.4% vs 2.8%), moderate (12.4% vs 10.5%), and minor (4.0% vs 3.9%), respectively (p = 0.86). Secondary clinical outcomes were also similar between groups (p > 0.05). Total costs for hospitalization were significantly greater for abciximab compared with eptifibatide ($16,383 +/- 6799 vs $14,115 +/- 6285; p < 0.001). Drug acquisition costs were also significantly greater for abciximab compared with eptifibatide ($508 +/- 159 vs $465 +/- 263; p = 0.003). CONCLUSIONS: In patients undergoing stent placement during PCI, abciximab and eptifibatide are comparable in terms of safety and effectiveness despite significant differences in hospitalization and acquisition costs.     

A multicenter study of the tolerability of tirofiban versus placebo in patients undergoing planned intracoronary stent placement

BACKGROUND: The use of intravenous glycoprotein IIb/IIIa-receptor antagonists has been shown to improve outcomes in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Tirofiban has shown benefit in a wide range of patients presenting with acute coronary syndromes. Although this agent has been used in patients undergoing percutaneous coronary intervention, a literature search identified no prospective data comparing tirofiban with placebo in patients undergoing planned intracoronary stent placement. OBJECTIVE: This study examined the tolerability of tirofiban in patients undergoing percutaneous intervention with planned intracoronary stent placement. METHODS: This was a multinational, multicenter, prospective, randomized, double-blind, placebo-controlled trial in patients scheduled to undergo PTCA with planned intracoronary stent placement. Patients were randomized in a 3:2 ratio to receive tirofiban as an intravenous bolus (10 microg/kg over 3 minutes) and maintenance infusion (0.10 microg/kg per minute for 36 hours) or a bolus and infusion of placebo. All patients received periprocedural aspirin and heparin and an optional postprocedural thienopyridine (ticlopidine or clopidogrel). Laboratory and safety monitoring were performed throughout the 36 hours after the procedure and at hour 40 or hospital discharge. The primary end point was the proportion of patients with bleeding, defined according to Thrombolysis in Myocardial Infarction (TIMI) trial criteria. The number of patients with cardiac events (death, myo- cardial infarction, urgent revascularization) during the first 30 days after stent placement was also assessed. RESULTS: Eight hundred ninety-four patients (536 tirofiban, 358 placebo) were enrolled, all of whom received aspirin and heparin periprocedurally and optional ticlopidine or clopidogrel after the procedure. No significant between-group differences were observed in the incidence of TIMI major bleeding (0.2% tirofiban, 0.6% placebo) or any TIMI bleeding (3.2% and 1.7%, respectively). The incidence of TIMI minor bleeding was higher with tirofiban than with placebo (2.8% vs 0.6%). The 30-day incidence of the composite end point of any cardiac event was 3.9% in both groups. CONCLUSIONS: On a background of concomitant aspirin, heparin, and a thienopyridine, tirofiban was generally well tolerated in patients undergoing PTCA with planned intracoronary stent placement. Further investigation is needed to ascertain the optimal dosing of tirofiban and heparin to achieve reductions in ischemic complications of intracoronary stenting with an acceptable incidence of bleeding complications.     

Influence of abciximab on evolution of left ventricular function in patients with non-ST-segment elevation acute coronary syndromes undergoing PCI after clopidogrel pretreatment: lessons from the ISAR-REACT 2 trial

Background

Abciximab reduced the combined endpoint of death, myocardial infarction (MI) and target vessel revascularization in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation after a 600-mg loading dose of clopidogrel. The aim of the present study was to investigate the impact of abciximab on the evolution of left ventricular ejection fraction (LVEF) in these patients.

Methods

The current study included 1,158 patients enrolled in the randomized, double-blind ISAR-REACT 2 (the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) trial who had paired angiograms obtained at baseline and 6?C8?months after randomization. Of them, 586 patients received abciximab and 572 patients received placebo. The primary outcome analysis was LVEF at 6?C8-month follow-up.

Results

Baseline LVEF was comparable in patients assigned to abciximab or placebo (53.2?±?12.6 vs. 53.7?±?12.1%; P?=?0.393). At 6?C8-month follow-up angiography, there was no difference in LVEF between the abciximab and placebo groups (55.4?±?11.5 vs. 55.8?±?11.2%; P?=?0.743). Subgroup analysis of patients with elevated baseline troponin (>0.03???g/L) also revealed comparable LVEF at follow-up in both treatment groups (P?=?0.527). The multivariate analysis identified age, arterial hypertension, prior MI, prior coronary artery bypass graft surgery, baseline LVEF, MI at 30?days and repeat PCI as independent correlates of follow-up LVEF.

Conclusion

Although abciximab reduced the 30-day and 1-year incidence of major adverse cardiac events in patients with NSTE-ACS undergoing primary PCI after pre-treatment with a 600-mg loading dose of clopidogrel, the agent did not improve or impact on the evolution of LVEF over 6?C8?months of follow-up.     

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.     

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.     

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.     

Clinical Characteristics,Management Strategies and Outcomes of Acute Myocardial Infarction Patients With Prior Coronary Artery Bypass Grafting

ObjectiveTo investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI).Patients and MethodsWe undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004–September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]).ResultsPatients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P<.001), all-cause mortality (OR, 0.45; 95% CI, 0.38 to 0.53; P<.001), and acute ischemic stroke (OR, 0.71; 95% CI, 0.59 to 0.86; P<.001) were observed in group 2 patients who underwent PCI compared with those managed medically without any increased risk of major bleeding (OR, 1.08; 95% CI, 0.94 to 1.23; P=.26).ConclusionsIn this national cohort, MI patients with prior-CABG had a higher risk profile, but similar in-hospital adverse outcomes compared with CABG-naive patients. Prior-CABG patients who received PCI had better in-hospital clinical outcomes compared to those who received medical management.     

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.     

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.     

替罗非班对急性心肌梗死患者介入术后心肌灌注和血小板活化功能的影响

目的 探讨替罗非班对急性心肌梗死(AMI)患者经皮冠状动脉介入治疗(PCI)后心肌灌注和血小板活化功能的影响.方法 80例AMI患者按随机数字表法分为2组,均于发病12 h内行急诊PCI术.对照组40例采用常规抗凝治疗(阿司匹林+低分子肝素+氯吡格雷).替罗非班组40例在对照组治疗的基础上于PCI术中冠状动脉内注入盐酸替罗非班10μg/kg,静脉维持量0.15 μg/(kg·min)36 h.观察2组PCI术后15 min梗死相关血管心肌灌注分级(TMPG)、治疗前及治疗7 d后血小板活化功能的变化、术后30 d内出血并发症及主要不良心脏事件(MACE)的发生情况.结果 替罗非班组PCI术后15 min TMPG灌注3级的百分比显著高于对照组[97.5%(39/40)与80.0%(32/40),x2=4.507,P＜0.05];治疗7 d后,替罗非班组的血小板活化指标血小板α颗粒表面膜糖蛋白、溶酶体膜糖蛋白、单核细胞血小板聚集体的阳性表达率显著低于治疗前和对照组[替罗非班组治疗后:(1.7±0.7)%、(1.5±0.7)%、(11.7±3.8)%,治疗前:(7.2±2.5)%、(6.9±1.8)%、(22.0±7.8)%,t值分别为13.398、17.683、7.508;对照组治疗后:(2.9±1.2)%、(3.9±0.6)%、(16.2±4.2)%,t值分别为5.463、16.468、5.025,P均＜0.01];治疗30 d后,替罗非班组心血管事件发生率显著低于对照组(0%与15.0%(12/40),x2=4.504,P＜0.05);2组出血并发症发生率比较差异无统计学意义(10.0%(4/40)与5.0%(2/40),x2=0.180,P＞0.05).结论 在AMI介入治疗中,应用盐酸替罗非班能改善心肌灌注,进一步抑制血小板的活化功能,减少PCI术后主要不良心脏事件的发生率,且不增加严重出血的发生.

Abstract：

Objective To evaluate the influence of tirofiban on myocardial perfusion through percutaneous coronary intervention (PCI) and platelet activation in patients with acute myocardial infarction (AMI). Methods Eighty patients with acute myocardial infarction who underwent emergency PCI within 12 hours were randomly divided into 2 groups due to the random number table method: tirofiban group (40 patients) and control group (40 patients). The control group received conventional anticoagulant therapy (aspirin + low molecular weight heparin + clopidogrel). The tirofiban group additionally received intracoronary tirofiban hydrochloride injection of 10 μg/kg PCI during PCI, intravenous maintenance dose of 0. 15 after PCI 15 mins, the changes of platelet activation before and after treatment 7 days,the bleeding complications and major adverse cardiac events (MACE) within 30 days after PCI. Results The TMPG 3 perfusion percentage of tirofiban group (97.5% ,39/40) after PCI 15 minutes was significantly higher than that (80. 0%,32/40) of the control group( x2 = 4. 507,P ＜ 0. 05 ) ;The expression positive rate of platelet activation CD62P,CD63, MPA of the tirofiban group after treatment of 7 days were ( 1.7 ± 0. 7 ) %, ( 1.5 ± 0. 7 ) % and ( 11.7 ±3.8)% ,respectively,which were significantly lower than those of before treatment ([7.2 ± 2. 5]%, [6. 9 ±1.8]% and [22. 0 ± 7. 8] %, respectivley) and those of the control group after treatment of 7 days ( [2. 9 ±1.2]% ,[3.9 ±0.6]% and [16.2 ±4.2]% ,respectivley)(t =5.463,16. 468 and 5.025, Ps ＜0.01 );The incidence of cardiovascular events of the tirofiban group (0) was significantly lower than that of the control group ( 15.0%, 12/40 ) after treatment of 30 days ( x2 = 4. 504, P ＜ 0. 05 ); The incidence of bleeding complications was not significant between the 2 groups ( x2 = 0. 180, P ＞ 0. 05 ). Conclusion The application of tirofiban hydrochloride in intervention in acute myocardial infarction can improve myocardial perfusion, and further inhibiting platelet activation and reduce the incidence of major adverse cardiac events after PCI while does not increase the incidence of severe bleeding.     

Bivalirudin in ST-segment-elevation myocardial infarction: for better or worse?

Bivalirudin and heparin are the major available parenteral anticoagulants for percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction. Even though hard clinical outcomes are comparable with both drugs, bivalirudin appears to be safer (less bleeding events) at the expense of lower short-term efficacy (more acute stent thrombosis events). The selection of anticoagulation during PCI in ST-segment-elevation myocardial infarction should be individualized, taking into account the patient’s ischemic and bleeding risk. In patients with increased bleeding risk, bivalirudin might be preferable to heparin, whereas in complex PCI with increased risk for stent thrombosis, heparin is preferable. Further clinical studies are needed to elucidate the role of these drugs in PCI for ST-segment-elevation myocardial infarction in the era of radial approaches, new potent antiplatelet agents and the use of glycoprotein IIb/IIIa inhibitors.     

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.