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Cerebral ischemia following clipping of cerebral aneurysms constitutes major cause of morbidity and mortality. Clip-related injury to vessel, postoperative clip rotation, prolonged temporary occlusion, intraoperative rupture, and vasospasm are some etiological factors compromising forward flow in parent or branch vessel. On suspicion of compromised forward flow, immediate intraoperative evaluation is done to detect the cause of vascular compromise and further management is done by microsurgical or endovascular means. We describe a case of ruptured distal anterior cerebral artery (ACA) aneurysm complicated by occlusion of ACA after surgical clipping. The patient was managed by endovascular means by combined technique of intra-arterial nimodipine, antiplatelet infusion, and mechanical clot disruption using J-tip microwire. [ABSTRACT FROM AUTHOR]

Background Early diagnosis of diffuse alveolar haemorrhage (DAH) can be extremely difficult, as the common clinical picture is often attributed to more common clinical conditions. High degree of suspicion is key to diagnosis which can be much more difficult during the coronavirus disease 2019 (COVID-19) pandemic. Case summary A 61-year-old man with inferolateral ST-segment elevation myocardial infarction treated by a stent to the left circumflex artery and intravenous abciximab treatment was started for the high thrombus burden. Two hours later, the patient developed dyspnoea and hypoxaemia. Chest examination revealed diffuse rales over both lung fields. Chest X-ray revealed bilateral diffuse alveolar infiltrates, while the echocardiography was normal. Chest computed tomography (CT) was performed and the 'crazy paving appearance', which is the typical radiological finding of COVID-19, was reported. The patient was considered to be suspected of COVID-19 and was transferred to a quarantine unit. Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) test was obtained and azithromycin and hydroxychloroquine were initiated. 48 h later, 2.6 mmol/L reduction was observed in haemoglobin levels and haemoptysis was developed. After the second negative RT-PCR with an interval of 24 h, CT was repeated and the patient was diagnosed to have abciximab-induced DAH. The patient was later followed up conventionally and discharged after two weeks without additional complications. Discussion DAH and COVID-19 might share common clinical and radiological findings during examination. The physicians must be aware of the high motivation of the COVID-19 pandemic which can lead to misdiagnosis by overlooking other important clinical conditions. [ABSTRACT FROM AUTHOR]

The antiplatelet landscape for the secondary prevention of ischemic stroke has changed significantly over the past decade. Poststroke dual antiplatelet regimens are becoming increasingly routine as supported by recent literature and guideline recommendations. Dual antiplatelet therapy after stroke generally consists of aspirin and clopidogrel and is considered in the short term after stroke in select populations including those with mild stroke or transient ischemic attack and in patients with severe intracranial atherosclerosis. When initiating dual antiplatelet therapy, factors that may increase a patient's risk of bleeding must be weighed against the patient's risk of future ischemic events. This review focuses on antiplatelet medications available in the United States with the aim to provide a summary of the available literature on poststroke dual antiplatelet therapy, pharmacological nuances of the agents, and reversal of antiplatelets in the setting of intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Background A stent is often necessary for the treatment of stroke. In such cases,it is essential for the patient to have antiplatelet therapy. There are several methods of antiaggregation, such as oral loading doses of aspirin and clopidogrel, intravenous aspirin, or intravenous glycoprotein Ilb/Illa receptor antagonists, such as abciximab. The aim of this study was to evaluate the incidence of symptomatic intracerebral hematoma (sICH) associated with our antiplatelet protocol: intravenous abciximab bolus at half the dose (0125 mg/ kg) at the time of the stenting procedure; oral aspirin (150 mg) and clopidogrel (75 mg) daily added the next day after CT shows no significant hematoma. Materials and methods Retrospective review of our database of endovascular management of large acute vessel occlusion treated with intravenous abciximab between January 2015 and March 2018. Demographics data, material, drugs, and complications were registered. Fisher tests were used to compare the incidence of sICH in the literature where abciximab 0.25 mg/kg plus maintenance doses are often administrated. Results Intravenous abciximab was administered to 99 patients. No sICH was observed. According to the European Cooperative Acute Stroke Study Scale, there were 8 cases of hemorrhagic infarction 1, 5 cases of hemorrhagic infarction 2, 4 cases of parenchymal hemorrhage 1, and no cases of parenchymal hemorrhage 2.A comparison between sICH with conventional antiplatelet doses based on the literature showed a statistically significant difference favoring our protocol. Conclusion In the endovascular treatment of acute ischemic stroke, a bolus dose of 0125 mg/kg of abciximab with no maintenance doses, followed by 150 mg of aspirin and 75 mg of clopidogrel orally the next day, is safe and effective. [ABSTRACT FROM AUTHOR]

The Solitaire (Medtronic Inc, Mansfield, Massachusetts, USA) is a stentriever device for endovascular treatment of acute ischemic stroke. Temporary endovascular bypass and mechanical thrombectomy are well-described applications of this device. However, few reports of permanent stent placement have been published. We present a series of five cases in which the Solitaire stent was implanted to restore distal flow after failure of conventional mechanical thrombectomy. All patients presented with large vessel occlusions with thrombi that were resistant to retrieval or suction-aspiration. Immediately after implantation the patients were given a loading dose of abciximab and then transitioned to dual antiplatelet therapy within 24 hours. Our series suggests that permanent deployment of the Solitaire may be considered as a bailout technique in the treatment of cerebral large vessel occlusion. Long-term antiplatelet therapy is required after deployment. [ABSTRACT FROM AUTHOR]

The present study investigated the predictive value of the platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism. From January 2014 to January 2016, 23 patients with postpartum deep vein thrombosis of lower extremity treated in the Department of Obstetrics of Beijing Chaoyang Hospital were as assigned as the observation group. At the same time, 25 cases with normal recovery were assigned as the control group. Blood samples were collected from all the subjects. The platelet aggregation rate was measured using a platelet aggregation apparatus. Plasma platelet activating factor (PAF) levels were measured by ELISA. The positive rate of platelet P-selectin (CD62p) and lysosomal membrane glycoprotein (CD63) was measured by flow cytometry. PI3K expression and AKt phosphorylation levels were measured by western blot analysis. The ROC curve was used to evaluate the value of the platelet aggregation rate in predicting postpartum deep vein thrombosis of lower extremity. The correlation between the platelet aggregation rate and PAF and PI3K/AKt expression was also analyzed. The cesarean section rate, platelet 5-min maximum aggregation rate, PAF level and the positive rate of CD62p and CD63 were significantly higher in the control than those in the observation group (P<0.05). Furthermore, the platelet aggregation rate was positively correlated with the expression of PAF, CD62p and CD63 (r=0.389, 0.451, and 0.452; all P<0.05). The platelet 5-min maximum aggregation rate for predicting postpartum deep vein thrombosis of lower extremity was reflected by the area under the ROC curve (AUC=0.797, P=0.000). The PI3Kp110β/β-actin and p-AKt/AKt ratio was significantly higher in the observation compared with the control group (P<0.05). In addition, the platelet aggregation rate was positively correlated with the expression of PI3K and phosphorylation level of AKt (r=0.441, 0.430; all P<0.05). The results suggested that platelet aggregation activity is elevated in postpartum deep vein thrombosis patients. It has a certain predictive value for the occurrence of postpartum deep vein thrombosis of lower extremity. Thuss, the PI3K/AKt signaling pathway may be one of the mechanisms of platelet aggregation. [ABSTRACT FROM AUTHOR]

Background and objective Acute thrombus formation following aneurysm treatment with the Pipeline embolization device (PED) is a potentially devastating complication that may result in significant thromboembolic sequelae if not promptly treated. We therefore evaluated PED cases complicated by acute thrombus formation at our institution, with an emphasis on identifying early angiographic signs that may portend this event. Materials and methods We retrospectively identified cases of acute thrombosis following PED placement in 100 consecutive procedures performed at our institution from a prospectively maintained clinical database. Angiographic findings were analyzed for early signs of acute thrombus formation. We also evaluated the efficacy of treatment of this complication with a glycoprotein IIb/IIIa inhibitor (abciximab), as well as the results of pre-procedure platelet inhibition testing. Results Acute thrombus formation was encountered in five patients following PED placement (5%). Early angiographic signs were present in all cases and included progressive stagnation of blood flow in covered side branches, occlusion of covered side branches, excessive stagnation of blood flow in the target aneurysm, as well as occlusion of the target aneurysm. These sequelae completely resolved following abciximab treatment in all five cases, with no permanent neurological morbidity or mortality. Four of the five patients had a pre-procedure P2Y12 value >200 (range 201-227). Conclusions Progressive stagnation or occlusion of covered side branches or target aneurysm are early angiographic signs of acute thrombus formation following PED placement and should prompt immediate treatment with a glycoprotein IIb/IIIa inhibitor. Platelet inhibition testing may help identify those patients who are at an increased risk for this complication. [ABSTRACT FROM AUTHOR]

Introduction: Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods: This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. Results: In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan-Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p=0.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73-1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79-1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71-1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). Conclusion: This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when used in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Objective:Acute occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. The aim of our study was to retrospectively delineate the feasibility of the combined use of emergent carotid stenting and intra-arterial (IA) Abciximab with intracranial revascularization in the setting of acute ischemic stroke and carotid occlusions at our institution. Methods:Eleven patients with complete cervical carotid occlusion with or without concomitant intracranial ICA and/or MCA occlusion were identified from a single center, retrospective review of patients admitted to the Stroke unit. We evaluated all cases for complications of emergent cervical ICA recanalization employing carotid stenting and IA Abciximab. Results:All patients had complete cervical carotid occlusion with (n = 8) or without (n = 3) concomitant intracranial ICA and/or MCA occlusion. Successful emergent cervical ICA recanalization was achieved in all cases. All patients were administered IA Abciximab (dose range 6–17 mg, average 11.4 mg) immediately following the cervical carotid stenting. There was complete recanalization in all patients with no procedural morbidity or mortality. A single case (1/11, 9%) developed asymptomatic hemorrhagic transformation. Upon discharge, 9 patients (9/11, 82%) had a mRS of 0–2 and 2 patients (2/11, 18%) had a mRS of 3. Conclusions:In acute ICA–MCA/distal ICA occlusions, extracranial stenting followed by intracranial IA Abciximab and thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted. [ABSTRACT FROM PUBLISHER]

Introduction Recent reports suggest that thromboembolic complications are associated with Pipeline embolization device (PED) placement cluster in P2Y12 hyporesponders. Objective To evaluate the role of P2Y12 hyporesponse in PED placement by retrospectively reviewing a single-center series of patients. Methods We retrospectively reviewed an institutional review board-approved database of patients with an aneurysm at a single institution and identified all patients with a measured P2Y12 reaction unit (PRU) >200 who had undergone anterior circulation PED placement. Events such as transient ischemic attack, stroke, and hemorrhage were identified as well as demographic and procedural details. Results Fifty-two patients with a PRU >200 had undergone anterior circulation PED placement. Four patients had prior subarachnoid hemorrhage (SAH) (8%) and 11 aneurysms (21%) had been previously treated. The average aneurysm size was 7.6 mm (±6.2). PED thrombosis occurred intraprocedurally in three patients, none of whom developed neurological deficits after abciximab administration. Treatment of all patients was successful and 48 procedures (92%) had no complications. One patient had a major stroke (2%) with permanent hemiparesis. There were three minor complications (6%): one minor stroke with a visual field cut, one 10 cc intracranial hemorrhage with transient left lower extremity weakness, and one transient neurological deficit not verified by imaging. No deaths or cases of SAH occurred. Conclusions P2Y12 hyporesponse (PRU>200) is not associated with increased periprocedural complications in a contemporary series of patients undergoing anterior circulation PED placement. Titration of antiplatelet medications to P2Y12 >200 remains unindicated and may increase the risk of hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Objectives: We sought to evaluate the patterns of use and outcomes associated with eptifibatide and abciximab administration among dialysis patients who underwent percutaneous coronary intervention (PCI).Background: Contraindicated medications are frequently administered to dialysis patients undergoing PCI often resulting in adverse outcomes. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that is often used during PCI and is contraindicated in dialysis.Methods: We included dialysis patients who underwent PCI from January 2010 to September 2015 at 47 hospitals in Michigan. We compared outcomes between patients who received eptifibatide compared with abciximab. Both groups required concurrent treatment with unfractionated heparin only. In-hospital outcomes included repeat PCI, bleeding, major bleeding, need for transfusion, and death. Optimal full matching was used to adjust for non-random drug administration.Results: Of 177 963 patients who underwent PCI, 4303 (2.4%) were on dialysis. Among those, 384 (8.9%) received eptifibatide and 100 (2.3%) received abciximab. Prior to matching, patients who received eptifibatide had higher pre-procedural hemoglobin levels (11.3 g/dL vs. 10.7 g/dL; P < 0.001) and less frequently had a history of myocardial infarction (36.5% vs. 52.0%; P = 0.005). After matching, there were no significant differences in in-hospital outcomes between eptifibatide and abciximab including transfusion (aOR: 1.15; 95%CI: 0.55-2.40; P = 0.70), bleeding (1.47; 0.64-3.40; P = 0.36), major bleeding (4.68; 0.42-52.3; P = 0.21), repeat PCI (0.38; 0.03-4.23; P = 0.43), and death (1.53; 0.2-9.05; P = 0.64).Conclusions: Despite being contraindicated in dialysis, eptifibatide was used approximately 3.5 times more frequently than abciximab among dialysis patients undergoing PCI but was associated with similar in-hospital outcomes. [ABSTRACT FROM AUTHOR]

Background Experience with intra-arterial infusion of abciximab for the treatment of endovascular thrombotic complications is limited to short case series. Our objective is to evaluate the safety and effectiveness of this drug for the treatment of thromboembolic complications during aneurysm coiling and to determine the risk factors. Methods From an aneurysm coiling database, patients treated with intra-arterial abciximab after having thrombotic complications during the coiling procedure were selected for analysis. Complications after using abciximab were categorized as hemorrhage, distal migration of the thrombus, and aneurysm recanalization. Results Fourteen coiling patients sustained a thromboembolic complication and were treated using intra-arterial infusion of abciximab and were subjected to further analysis. The age range was 48–76 years. Three patients were male. Seven patients had subarachnoid hemorrhage. Only complete recanalization was associated with clinical improvement, but this occurred in only 4 patients (28.5%). Partial or complete recanalization occurred in 13 patients (93%). Eight patients (57%) had complications derived from the infusion. Three patients had aneurysm recanalization, 3 patients had distal migration of the thrombus and 1 patient had a hemorrhagic complication. Eight patients demonstrated acute infarcts related to the occluded vessel, whereas 7 patients made a good functional recovery. Conclusion Successful recanalization of a vessel occluded by thrombus formation during aneurysm coiling using abciximab (Reopro) infusion is less than optimal. There are risks related to abciximab, including bleeding and aneurysm recanalization. [ABSTRACT FROM AUTHOR]

Aims The aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence. Methods The present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System. Antiplatelet drug users were classified as persistent users (gap between prescriptions ≤90 days), nonpersistent users (>90-day gap and no refills), and restarters (a new prescription after a >90-day gap). The association between potential determinants and antiplatelet nonpersistence was analysed using Cox regression. Results The proportions of persistent users decreased from 84.0% at the 1-year follow-up to 32.8% at 10 years for any antiplatelet drug, and 77.3% to 27.5% for aspirin; and 39.0% to 6.4% for clopidogrel at 6 years. Most nonpersistent users restarted antiplatelet drugs later, leading to 89.3% overall antiplatelet drug users at 10 years after MI. Diabetes (hazard ratio [HR] 0.44; 0.32-0.60), hypertension (HR 0.77; 0.60-0.99), hypercholesterolaemia (HR 0.49; 0.39-0.62) and more recent MI diagnosis period (2003-2007: HR 0.69, 0.61-0.79; 2008-2010: HR 0.38, 0.19-0.77, compared to ≤ 2002 period) lowered the risk of antiplatelet nonpersistence, while vitamin K antagonist (VKA) comedication (HR 18.97; 16.91-21.28) increased this risk. Conclusions A large proportion of patients with a first MI still used antiplatelet drugs after 10 years. The frequent discontinuations during this time frame are expected to reduce the effectiveness of antiplatelet drugs as secondary prevention of cardiovascular diseases. Diabetes, hypertension, hypercholesterolaemia, VKA comedication and MI diagnosis period were determinants of antiplatelet nonpersistence. [ABSTRACT FROM AUTHOR]

Background Abciximab is used to treat thromboembolic complications of neuroendovascular procedures, but outcomes of treatment are not well defined. Objective To examine the angiographic and clinical outcomes based on route of abciximab administration and degree of vessel recanalization. Materials and methods A prospectively maintained database of neuroendovascular procedures performed between January 2004 and May 2015 was retrospectively reviewed to identify cases with thromboembolic complications treated with abciximab. In these cases, route of administration, degree of vessel recanalization, and presence or absence of infarction were determined. A meta-analysis of similar cases in the literature was also performed. Results Abciximab was administered in 0.24% (47 of 19 566) of procedures to treat thromboemboli in 59 vessels. Angiographic improvement was seen in 94% after IA therapy and 79% after IV therapy (p=0.133). In our meta-analysis of 391 treated patients, angiographic improvement was greater after IA (91.7%) than IV (77.4%) treatment (p<0.001). Postprocedural infarction occurred more frequently with distal lesions (42%) than local lesions (12%) (p=0.014), and occlusive lesions (36%) than non-occlusive lesions (4.8%) (p=0.010). Infarction was significantly less common with complete angiographic resolution (0%) than with partial or no improvement (54%) (p<0.001). Symptomatic intracranial hemorrhage occurred in 2.1%. Conclusions Abciximab produces a high rate of angiographic improvement and a low incidence of postprocedural infarct in neuroendovascular procedures complicated by thromboemboli. IA abciximab produces greater angiographic improvement than IV treatment. Postprocedural infarction is less common in patients with complete angiographic response than in those with partial or no response. [ABSTRACT FROM AUTHOR]

Objective The present study investigated whether the glycoprotein (GP)IIb/IIIa receptor blocker abciximab might be a successful bridging strategy to achieve adequate levels of platelet inhibition rapidly in cases where prasugrel is used in morphine-pretreated ST-elevation myocardial infarction (STEMI) patients. Methods In a prospective observational cohort study, 32 patients presenting with STEMI were given prasugrel at a loading dose of 60 mg. Patients were stratified into four groups, according to morphine and/or abciximab use. Adenosine diphosphate (ADP)-induced platelet aggregation was measured at four time points: at baseline, and at 2 h, 1 day and 2 days after prasugrel loading. Results Morphine use was associated with a three-fold higher level of ADP-induced platelet aggregation 2 h after prasugrel loading compared with no morphine/no abciximab ( P = 0.019). However, when abciximab was infused in the catheterization laboratory, the effect of morphine on ADP-induced platelet aggregation disappeared ( P = 0.884). This interaction was also seen in the presence of high on-treatment platelet reactivity (HTPR) at 2 h; while HTPR was seen in 88% of morphine users/no abciximab users, it was found in only 17-20% in the three other groups ( P = 0.003). The effect of morphine disappeared by day 1 - 2. Conclusion The infusion of the GPIIb/IIIa receptor blocker abciximab allows immediate and efficient platelet inhibition in STEMI patients concomitantly receiving the oral ADP receptor blocker prasugrel and morphine. [ABSTRACT FROM AUTHOR]

Platelet aggregation is a crucial feature in coronary artery thrombus formation and is a major causative factor in both acute coronary syndromes (ACS) and reocclusion after percutaneous coronary interventions (PCI). The glycoprotein (GP) IIb/IIIa (αIIbβ3) integrin receptor is the pivotal mediator of platelet aggregation. In late 1990s, the introduction of GP IIb/IIIa inhibitors (GPI) was associated with a reduction of ischemic complication, and a clear clinical benefit in PCI during ACS, for both non ST-elevation (NSTE) and ST-segment elevation myocardial infarction (STEMI). The currently available GPI (abciximab, eptifibatide and tirofiban) tended to be replaced in the current therapy of STEMI by different agents and this is in part related to the effectiveness and to the potential adverse effects (thrombocytopenia and bleeding). There might be a certain level of variability among these agents and here we have reviewed only abciximab in detail. Interestingly, however, the story may not be entirely different from that of positive inotropic agents in the context of acute ischemia where the potent action to sustain left ventricular function had an arrhythmogenic counterpart to evaluate and take into consideration and therefore therapeutically it will always be necessary to weigh benefits and harms if actions are expected by relatively potent agents. [ABSTRACT FROM AUTHOR]

Cerebral sinus venous thrombosis (CSVT) is a recognized cause of childhood and neonatal stroke. More than 50% of neonates have a poor outcome, and mortality is high. Coma is a predictor of death in neonatal CSVT. We present the case of a 9-day-old infant, who presented in coma and was treated successfully with a combination of mechanical thrombectomy using the MindFrame System via the right jugular vein, local infusion of recombinant tissue plasminogen activator and abciximab, as well as anticoagulation. In this case, aggressive thrombectomy and thrombolysis achieved complete neurologic restoration safely and quickly. [ABSTRACT FROM AUTHOR]

Introduction There are limited data regarding the possible benefits of abciximab in children with Kawasaki disease (KD), who developed serious cardiac abnormalities non-responsive to standard treatment. Materials and methods We retrospectively identified children with KD who were treated with abciximab from 2007 to 2015. Data regarding clinical course, treatment, echocardiographic data and follow-up at 1 and 6 months were retrieved. Results During the study period, fifteen children were identified who were diagnosed with KD and were given abciximab. The median age at onset of symptoms was 11 months (range: 2 months–6 years). The median day of disease at admission was 10 days (range: 4–26 days) and the median day of administration of abciximab was 17 days (range: 9–40). Twelve children were diagnosed with complete and three with incomplete KD. Aneurysms were found in 8 children: 2 had ectatic coronary arteries and 5 presented with both ectasia and aneurysms. At 1 month follow-up, echocardiographic findings showed regression in the size of aneurysms in 11 children, resolution of the aneurysms or ectasia of coronary arteries in 3 children, while one child who could not take aspirin because of G6PD deficiency died. After 6 months of follow-up, echocardiographic findings showed resolution of coronary abnormalities in 12 (80%) children, whereas 2 children (13.3%) presented with significant regression of aneurysms. Conclusions Abciximab may have an important role in the management of severe cardiac complications of KD, although prospective randomized controlled studies are needed to fully evaluate its role. [ABSTRACT FROM AUTHOR]

Aims To compare three glycoprotein IIb/ IIIa receptor antagonists ( GPIs) in terms of platelet inhibition and major adverse cardiac events ( MACEs), and assess the rate of bleeding and MACEs between GPIs and coadministered P2Y12 agents. Methods Eighty-three acute coronary syndrome ( ACS) patients undergoing percutaneous coronary intervention ( PCI) with planned GPI use were randomized to receive high-dose bolus tirofiban, double-bolus eptifibatide, or abciximab followed by a 12-hour infusion. Glycoprotein IIb/ IIIa platelet receptor inhibition was measured at baseline and at 10 minutes, 1 hour, and 24 hours postbolus dose. Major adverse cardiac events and bleeding complications at 30 days were documented. The incidence of MACEs and bleeding in patients receiving ticagrelor or prasugrel were compared to those given clopidogrel. Results There were no statistically significant differences in platelet inhibition between GPIs at 10 minutes ( P=.085) and 1 hour ( P=.337). At 24 hours, abciximab achieved statistically significantly higher median [interquartile range] platelet inhibition (75 [65-88]%) compared to tirofiban (28 [3-56]%; P<.0001) and eptifibatide (44 [31-63]%; P=.007). There were no differences in bleeding or MACEs depending on GPI or P2Y12 inhibitor administered. Conclusions Glycoprotein receptor inhibitors achieve similar levels of platelet inhibition at 10 minutes and 1 hour; however, abciximab maintains this benefit 24 hours after bolus dose. We did not witness an increased rate of bleeding in patients given new potent P2Y12 inhibitors and a GPI in the modern era. [ABSTRACT FROM AUTHOR]

Background Standard pretreatment with dual antiplatelet medication (DAPM) was compared with a standalone intraprocedural abciximab bolus for the prevention of thromboembolic and hemorrhagic events during endovascular stenting of unruptured intracrania aneurysms. Materials and methods We treated 94 patients with 99 aneurysms with intracranial stenting (with or without coiling). Patients were either pretreated with DAPM daily for ≥3 days before stenting (pretreatment group) or received an abciximab bolus during or immediately after stent placement followed by postoperative DAPM (abciximab group), at the treating physician's discretion. Twenty patients underwent immediate postoperative MRI. Demographic, clinical, and radiological information and periprocedural complications were recorded. Results There were 52 procedures in the pretreatment group and 47 in the abciximab group. More flow-diverting stents were placed in the pretreatment group than in the abciximab group (45 vs 23, p<0.001), and the aneurysm diameter was larger (11.2±6.7 vs 8.3 ±4.7 mm, p=0.01). There were 11 thrombotic and 7 access site complications, with no significant difference between the groups (p>0.99 and p=0.12, respectively). There were no intracranial hemorrhages. In patients with postoperative MRI, there was no difference in the presence of diffusion-restricted lesions between groups (p=0.20). Multivariate analysis of a composite of any complication did not show significant associations with aneurysm or patient variables in either group. Conclusions Standalone intraprocedural abciximab bolus was not associated with an increased rate of complications compared with pretreatment with DAPM for unruptured intracranial aneurysm stenting. [ABSTRACT FROM AUTHOR]

Background: Diabetic patients are at increased risk for future cardiovascular events after ST-segment elevation myocardial infarction (STEMI). Administration of an intracoronary abciximab bolus during primary percutaneous coronary intervention (PCI) may be beneficial in this high-risk subgroup.Objectives: This study sought to report the 1-year clinical outcomes and cardiac magnetic resonance (CMR) findings in STEMI patients with and without diabetes randomized to intracoronary or intravenous abciximab bolus at the time of primary PCI.Methods: Patient-level data from 3 randomized trials were pooled. The primary endpoint was the composite of death or reinfarction. Comprehensive CMR imaging was performed in 1 study.Results: Of 2,470 patients, 473 (19%) had diabetes and 1,997 (81%) did not. At 1 year, the primary endpoint was significantly reduced in diabetic patients randomized to intracoronary abciximab compared with those randomized to intravenous bolus (9.2% vs. 17.6%; hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.83; p = 0.009). The intracoronary abciximab bolus did not reduce the primary endpoint in patients without diabetes (7.4% vs. 7.5%; HR: 0.95; 95% CI: 0.68 to 1.33; p = 0.77), resulting in a significant interaction (p = 0.034). Among diabetic patients, intracoronary versus intravenous abciximab bolus was associated with a significantly reduced risk of death (5.8% vs. 11.2%; HR: 0.51; 95% CI: 0.26 to 0.98; p = 0.043) and definite/probable stent thrombosis (1.3% vs. 4.8%; HR: 0.27; 95% CI: 0.08 to 0.98; p = 0.046). At CMR (n = 792), the myocardial salvage index was significantly increased only in diabetic patients randomized to intracoronary compared with intravenous abciximab (54.4; interquartile range: 35.1 to 78.2 vs. 39.0, interquartile range: 24.7 to 61.7; p = 0.011; p for interaction vs. no diabetes = 0.016).Conclusions: In diabetic patients with STEMI, the administration of intracoronary abciximab improved the effectiveness of primary PCI compared with the intravenous bolus. [ABSTRACT FROM AUTHOR]

Glycoprotein (GP) IIb/IIIa inhibitors block platelet aggregation, reducing thrombotic events in acute coronary syndrome. They are most often utilized in patients who likely have an intracoronary thrombus. Tirofiban, eptifibatide, and abciximab are the three GP IIb/IIIa inhibitors approved for use in the United States. Each agent has unique pharmacological properties. They all have a rapid onset and are most often utilized in conjunction with heparin. Tirofiban, in particular, fell out of favor due to inferior dosing with its original Food and Drug Administration (FDA) approved indication, but has re-emerged in the market with a high-dose bolus regimen that is considered equally as effective as the FDA approved dosing regimens of other GP IIb/IIIa inhibitors. This review looks at pharmacological properties of all three agents, significant clinical trials associated with their use, and their place in current guidelines. [ABSTRACT FROM AUTHOR]

Background: Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) poses a high-risk for distal coronary thromboembolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and efficacy of these drugs to improve outcomes in this setting are understudied.Methods: Patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of ≥1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1:1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30days and up to 1year.Results: The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57-2.21, p=0.73). At 1-year follow-up, MACCE rates were also similar (32.5% vs. 33.9%, HR: 0.97, 95% CI: 0.59-1.59). Major bleeding (BARC types 3a-c) was higher in the abciximab group (11.9% vs. 4.2%, OR: 2.80, 95% CI: 1.01-7.77). Ischemic outcomes did not differ among patients with acute coronary syndromes.Conclusion: The use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding. [ABSTRACT FROM AUTHOR]

Background Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. Objectives To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. Results Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26–0.99; p = 0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26–1.20; p = 0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07–0.99; p = 0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n = 2574). Conclusions In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist remains a mainstay in the prevention of ischemic events following coronary stent placement. Significant controversy exists regarding the optimal management of high platelet reactivity despite antiplatelet therapy; however this finding has been consistently associated with poor clinical outcomes including greater risk of stent thrombosis and myocardial infarction. Variability in antiplatelet effects of clopidogrel and prasugrel has been linked to genetic polymorphisms and potential drug–drug interactions. Both of these factors have significant influence on the cytochrome P-450 enzyme system activity of the liver responsible for their biotransformation to the active form of both drugs. Very little has been publicized regarding differences in antiplatelet effects which may be associated with conditions in which the functional capacity of the liver may be temporarily compromised. Patients who present with cardiogenic shock due to acute coronary syndromes have evidence of multiorgan dysfunction including liver dysfunction that may affect the activity of these drugs. This review aims to explore existing evidence and propose additional considerations to the selection of antiplatelet therapy in patients with cardiogenic shock who receive catheter-based revascularization and stent placement. [ABSTRACT FROM PUBLISHER]

Background: Antiplatelet (AP) therapy is well established for the secondary prevention of acute coronary events. However, patients may discontinue treatment, often owing to gastrointestinal (GI) complications, leaving them at elevated risk of recurrent cardiovascular events. Objectives: This descriptive retrospective study assessed trends in prescription of AP agents and coprescription of gastroprotective therapy, after an acute coronary event. Discontinuation of AP therapy within 2 years of an event and factors predicting discontinuation were investigated. Methods: The study was conducted in a UK primary care setting from 2000 to 2008; a total of 27 351 patients aged 50 to 84 years were included in the analysis. Main outcome measures were exposures to low-dose acetylsalicylic acid (ASA), clopidogrel, and proton pump inhibitors (PPIs). Results: At 90 days after an acute coronary event, 85.9% of patients had been prescribed some form of AP therapy and 33.6% of patients who were issued at least 1 ASA prescription in this period were also issued a PPI prescription. The use of dual antiplatelet therapy (DAT) 90 days after an event increased from 2% in 2000 to over 50% in 2008. An estimated 15.1% of patients on ASA monotherapy and 37.5% on DAT discontinued treatment within 1 year. A bleeding event during follow-up, including upper GI bleeding or hemorrhagic stroke, was the strongest predictor of discontinuation. Conclusion: Although most patients were prescribed AP therapy in the 90 days following an acute coronary event, a substantial proportion discontinued DAT or ASA monotherapy within 1 year. It is essential that physicians consider strategies to reduce the risk of discontinuation of AP therapy. [ABSTRACT FROM PUBLISHER]

The article presents a study on intra-arterial Abciximab injection and its safety in the endovascular treatment of torn aneurysms. It highlights its management of thromboembolic disease in the therapy. An overview of data analysis and ventricular shunting that involves dichotomized patients is also presented.

A series of novel 2-aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma using light transmission aggregometry. Among the tested derivatives, compounds Ia, Ib, IB and II16 exhibited the highest antiplatelet aggregation activity (36.75, 72.4, 62.5 and 80 μM). None of the compounds showed satisfactory activity against the aggregation induced by ADP but acceptable activities were observed against the aggregation induced by arachidonic acid. 2- aminopyrimidines were more active than 4,6- diaminopyrimidines in this respect. [ABSTRACT FROM AUTHOR]

Contrasting data have been so far reported on facilitation with glycoprotein IIb-IIIa inhibitors (GpIIbIIIa) in patients who underwent primary percutaneous coronary intervention. However, it has been demonstrated a time-dependent composition of coronary thrombus in ST-segment elevation myocardial infarction, with more platelets in the first hours. Subsequently, the benefits of early administration of GpIIbIIIa may be affected by the time from symptoms onset to GpIIbIIIa, that therefore is the aim of this study. Our population is represented by 814 patients who underwent GpIIbIIIa facilitated primary angioplasty included in the Early glycoprotein IIb-IIIa inhibitors in primary angioplasty database. Patients were divided according to quartiles of time from symptom onset to GpIIbIIIa administration (≤65 minutes; 65 to 100 minutes; 101 to 178 minutes; and >178 minutes). Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Time from symptoms onset to GpIIbIIIa was linearly associated with hypertension, diabetes, hypercholesterolemia, and previous myocardial infarction but inversely associated with smoking. Abciximab was more often administrated later from symptoms onset. Time from symptoms onset to GpIIbIIIa was significantly associated with the rate of preprocedural recanalization (thrombolysis in myocardial infarction [TIMI] 2 to 3; p <0.001), postprocedural TIMI 3 flow (p <0.001), the rate of complete ST-segment resolution (p <0.001), and the rate of myocardial blush grade 2 to 3 (p <0.001) and inversely associated with the occurrence of distal embolization (p <0.001). Follow-up data were collected at a median (twenty-fifth to seventy-fifth) of 360 (30 to 1,095) days. A total of 52 patients had died. Time to GpIIbIIIa had a significant impact on mortality (hazard ratio [95% confidence interval] 1.46 [1.11 to 1.92], p = 0.007) that was confirmed after correction for baseline confounding factors (adjusted hazard ratio [95% confidence interval] 1.41 [1.02 to 2.21], p = 0.042). In conclusion, this study showed that in patients who underwent primary angioplasty with upstream GpIIbIIIa, time from symptoms onset to GpIIbIIIa strongly impacts on preprocedural recanalization, distal embolization, myocardial perfusion, and long-term survival. [ABSTRACT FROM AUTHOR]

Purpose: This review discusses the role of clinical pharmacology in the development of low-dose aspirin and other antiplatelet agents during the past 30 years, emphasizing the main determinants of several success stories as well as of complete failures in the field. Methods: The author employs personal appraisal of the literature, with emphasis on personal contributions to the field. Findings: Low-dose aspirin provides an interesting paradigm of the independent development of a "new" antiplatelet agent by the medical/scientific community. Aspirin "resistance," improved dosing regimens for personalized therapy, and chemoprevention of colorectal cancer are thoroughly discussed. The industrydriven development paradigm includes 12 mechanismbased antiplatelet agents. Of those completing Phase 3, only 6 have been approved for the acute treatment or secondary prevention of atherothrombosis. Inadequate Phase 2 studies were largely involved in Phase 3 failures. Implications: The design of mechanism-based pharmacodynamic biomarkers and sophisticated Phase 2 investigations appear as an important key to successful drug development in this field. Clinical pharmacology has an excellent track record in this endeavor, and its role needs to be expanded, as suggested by the case studies discussed in this review. Finally, the choice of appropriate platelet-dependent end points and homogeneous clinical settings for Phase 3 trials not only represent desirable objectives for an integrated scientific and regulatory discussion but also deserve proper ethical consideration by all stakeholders to avoid an unacceptable burden of drug toxicity and an unsustainable waste of financial resources. [ABSTRACT FROM AUTHOR]

Objectives: Retrospective pooled analysis of data from published prospective studies and randomized phase 1 and 2 trials was done to assess efficacy and safety profile of intravenous combination therapy [glycoprotein IIb/IIIa inhibitors and IV tissue plasminogen activator (tPA)] in management of acute ischemic stroke. Materials and Methods: We searched Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, and EMBASE databases; two reviewers independently selected studies reporting safety endpoints and outcome measures in acute ischemic stroke patients treated with combination therapy. tPA arm of the National Institute of Neurological Disorders and Stroke (NINDS) tPA trial was included in tPA-only group. Weighted means and proportions were calculated for numeric and categorical variables respectively. Bivariate analysis using Fisher's exact test was done to compare baseline descriptors, safety endpoints, and outcome measures. Results: Combination therapy arm included 188 patients and IV tPA arm had 21 8 patients. Mean National Institutes of Health Stroke Scale (NIHSS) in two groups were 12.8 and 14.6, respectively. Mean time-to-treatment was 2.3 hours in combination therapy arm and 2.55 hours in tPA arm. Treatment with combination therapy was associated with significant reduction in rate of symptomatic intracranial hemorrhage (sICH) [odds ratio (OR) 0.26, 95% cumulative incidence (CI) 0.07 0.83, P value 0.01). Difference in better functional outcome at 90 days (OR 0.87, 95% CI 0.59-1.30, P value 0.54) and death at 90 days (OR 1.16, 95% CI 0.69-1.93, P value 0.60) were not significantly different in two groups. Conclusion: Combination of low dose IV TPA with glycoprotein IIb/IIIa inhibitors is associated with reduction in sICH rates in patients with acute ischemic stroke as compared to standard dose of IV tPA. [ABSTRACT FROM AUTHOR]

Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI). However, the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied. The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of randomized trials comparing intracoronary with intravenous abciximab bolus administration. A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included. Diabetes was present in 578 patients (19%). The primary outcome was mortality after a median follow-up period of 375 days. Secondary end points were reinfarction and stent thrombosis. In patients without diabetes, IRA occlusion versus no occlusion was not associated with increased rates of mortality (4.3% vs 2.7%, p = 0.051) and reinfarction (3.3% vs 2.5%, p = 0.33). Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality (10.6% vs 4.6%, p = 0.01) and reinfarction (5.6% vs 2.1%, p = 0.03). Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic (2.1% vs 1.0%, p = 0.04) and diabetic (3.2% vs 0.8%, p = 0.05) cohorts. Interaction analysis demonstrated that the risk for death and reinfarction was significantly increased when diabetes and IRA occlusion occurred concomitantly. In conclusion, patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfarction. Preprocedural IRA occlusion increased the risk for stent thrombosis, irrespective of diabetic status. [ABSTRACT FROM AUTHOR]

Background and objective Reducing bleeding events is a priority in patients diagnosed with acute coronary syndromes (ACS). The effectiveness of optimization measures for reducing abciximab-related bleeding was evaluated through the implementation of a pilot program developed by the Pharmacy and the Cardiology Departments at a tertiary-care hospital. Main outcome measure Percentage of bleeding events. Results Intervention was effective in reducing the incidence of the three factors associated with an increased risk of bleeding between the pre-intervention phase (n = 86) and the post-intervention phase (n = 73): unknown body weight (24.4 vs. 1.4 %, p = 0.0001), overdosing (31.4 vs. 0 %, p < 0.0001) and combination with bivalirudin (12.8 vs. 1.4 %, p = 0.016). Bleeding events associated with these factors were numerically reduced in all three cases but these differences were not statistically significant between both periods. Conclusion The implementation of a multidisciplinary prevention program can reduce situations associated with an increased risk of bleeding in patients treated with abciximab. Larger scale trials are needed to confirm whether such programs can also reduce the incidence of bleeding at a statistically significant level. [ABSTRACT FROM AUTHOR]

Introduction of antiplatelet agents has contributed substantially to improve the outcome of patients with acute coronary syndromes. Meta-analysis of the studies on abciximab administration during primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI) has clearly confirmed the mortality benefit associated with intravenous bolus and infusion of abciximab compared to placebo. Recently, introduction of new oral P2Y12 inhibitors (prasugrel, ticagrelor), with a faster and more pronounced antiplatelet effect, have decreased the use of abciximab even in patients with STEMI. However, recent studies have shown a delayed onset of antiplatelet effect of new oral antiplatelet drugs in the setting of STEMI, especially in patients with hemodynamic compromise. Thus, the use of abciximab as an intravenous agent should be strongly considered when oral P2Y12 inhibitors might fail or cannot be given before primary PCI for STEMI. An additional benefit of abciximab administration was reported when abciximab was given early, before primary PCI, compared to typical periprocedural use. To the contrary, no clear clinical benefit was confirmed for intracoronary administration of abciximab compared with intravenous administration. Future studies should focus on the role of abciximab given on top of new oral P2Y12 inhibitor (prasugrel, ticagrelor) or used as an alternative to an intravenous P2Y12 inhibitor (cangrelor). Undoubtedly, the results of these studies will change everyday practice of STEMI treatment. [ABSTRACT FROM AUTHOR]

Prasugrel is more potent than clopidogrel, but it is not known whether this translates into clinical benefit in patients undergoing primary percutaneous coronary intervention (PCI) with bivalirudin for ST elevation myocardial infarction. In the Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction trial, 452 patients with anterior STEMI undergoing primary PCI with bivalirudin were randomized to intralesional abciximab or placebo and to thrombus aspiration or no aspiration. Clopidogrel or prasugrel were administered at physician discretion. The primary end point was infarct size at 30 days by cardiac magnetic resonance imaging. Clinical events at 30 days and 1 year were independently adjudicated. Propensity score was used to adjust for nonrandom allocation of the drugs. Prasugrel and clopidogrel were administered to 155 patients (34.3%) and 297 patients (65.7%), respectively. Patients receiving prasugrel were younger with higher left ventricular ejection fraction and greater use of drug-eluting stents. Prasugrel-treated patients had higher rates of procedural success (94% vs 89%, p [ 0.03), Thrombolysis In Myocardial Infarction (TIMI) 3 flow (95% vs 90%, p [ 0.06), and lower corrected TIMI frame counts (21 ± 6 vs 23 ± 11, p [ 0.008). At 30 days, infarct size was marginally lower in the prasugrel group (median [interquartile range][16.4% [6.5 to 20.0] vs 17.6% [8.1 to 25.7], p [ 0.06). At 1 year, prasugrel group had significantly fewer deaths (1.3% vs 8.3%, p [ 0.004) and fewer episodes of severe heart failure (2.0% vs 7.7%, p [ 0.02). These findings persisted after propensity score adjustment. There were no significant differences in major bleeding. Stent thrombosis was 0% versus 2.5%, respectively, p [ 0.054. We conclude that prasugrel was associated with improved efficacy and similar safety compared with clopidogrel in patients undergoing primary PCI with bivalirudin. [ABSTRACT FROM AUTHOR]

Objectives To study an alternative strategy for the treatment of radial artery occlusion (RAO) using balloon angioplasty and intrathrombus administration of abciximab. Background RAO is a well-described complication of transradial procedures. The optimal method to restore the patency of the radial artery following its occlusion remains unclear. Spontaneous recanalization can occur in some patients and systemic anticoagulation can be recommended but is often unsuccessful. Methods A retrospective review of all patients in our database from 2009 to 2013 with RAO who underwent treatment with balloon angioplasty and intra-arterial abciximab administered directly at the site of occlusion. Results Four patients with symptomatic RAO following transradial catheterization were treated with balloon angioplasty and a 90-second intrathrombus infusion of abciximab. All procedures were successful and patency was documented the following day with duplex sonography and again at follow-up (mean 189 days). The patients also remained free of symptoms at follow-up. The fifth patient was treated with balloon angioplasty alone. This patient suffered symptomatic reocclusion of the radial artery. Conclusions Balloon angioplasty and intrathrombus administration of abciximab via a catheter appears to be a safe, effective, and durable technique for reestablishing the patency of an occluded radial artery following transradial catheterization. Larger studies are needed to confirm our findings and establish the role for this technique in an algorithm for treatment of RAO. (J Interven Cardiol 2014;27:217-222) [ABSTRACT FROM AUTHOR]

Objective--To determine effects of the glycoprotein IIb/IIa receptor antagonists abciximab and eptifibatide on in vitro inhibition of cat platelets. Sample--Venous blood samples from 10 healthy cats. Procedures--Blood samples were anticoagulated with hirudin. Aliquots of whole blood from each cat were allocated to 5 treatments (baseline, 50 µg of abciximab/mL, abciximab volumetric control treatment, 4µM eptifibatide, and eptifibatide volumetric control treatment). Impedance platelet aggregometry was performed with 6.5µM ADP or 32µLM thrombin receptor activator peptide (TRAP). Magnitude of platelet aggregation was determined by measuring the area under the curve 15 minutes after addition of ADP or TRAP. Results--Eptifibatide caused a significant reduction in platelet aggregation, compared with baseline values, for aggregometry with both ADP (median, 50.0; range, 8 to 122 [baseline median, 306.0; baseline range, 130 to 664]) and TRAP (median, 75.5; range, 3 to 148 [baseline median, 219.0; baseline range, 97 to 578]). There was no significant difference in platelet aggregation with abciximab, the abciximab volumetric control treatment, or the eptifibatide volumetric control treatment for aggregometry with ADP or TRAP. Conclusions and Clinical Relevance--Eptifibatide caused a significant reduction in platelet aggregation in vitro, but there was no identifiable antiplatelet effect for abciximab. Eptifibatide and abciximab have different binding and inhibitory actions; therefore, it can be hypothesized that abciximab would be ineffective in cats because of a lack of receptor binding, reduced binding kinetics, or lack of downstream signaling. Eptifibatide may be useful in identifying hyperreactive platelets in cats in an in vitro platelet inhibitory assay. [ABSTRACT FROM AUTHOR]

A murine monoclonal antibody (mAb) 3C7 against integrin αIIbβ3 was previously obtained as a potential antithrombotic agent in our laboratory. The epitope of 3C7 is a specific conformation of the αIIbβ3 complex, but not either of the two subunits, which makes it different from abciximab, a supplementary antibody drug used in percutaneous coronary intervention which has a cross-reaction with other integrins sharing the β3 subunit. To reduce the human anti-mouse antibody reactions of 3C7, the variable regions of this antibody were cloned and fused with the constant counterparts of human IgG1. Two vectors of light and heavy chains were constructed and co-transfected into CHO- dhfr cells. The chimeric antibody c3C7 was purified and the properties of c3C7 were compared with 3C7. Identical to its parent antibody 3C7, c3C7 binds to the αIIbβ3 complex, but not to either of the subunits. The K value of c3C7 was in the same order of magnitude as 3C7 (1.570 ± 0.326 vs 0.780 ± 0.182 nmol/L). Human platelet aggregation induced by adenosine diphosphate was effectively inhibited by c3C7 in a dose-dependent manner. In conclusion, after the modification, c3C7 retained the properties of its parent mAb with no loss of its biological activity. Therefore, c3C7 has the potential to become a novel agent for the treatment of thrombosis. [ABSTRACT FROM AUTHOR]

Objective To systematically examine the evidence on nontraditional uses of viscoelastic coagulation monitoring in veterinary species. Design Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Setting Academic and referral veterinary medical centers. Results Databases searched included Medline, CAB abstracts, and Google Scholar. Conclusions Nontraditional assays identified included thrombelastography (TEG)-PlateletMapping (PM), functional fibrinogen assessment, and rapid-TEG (r-TEG). Direct veterinary evidence was found for only the ADP-activated PM, which appears to generate valid data in dogs but not cats or horses. Arachidonic acid activated PM shows high variability and requires further assessment and validation in veterinary species. Functional fibrinogen assays may be performed in veterinary species but may require modification due to species differences in response to abciximab. While tissue factor (TF)-activated TEG has been well described in the veterinary literature, the specific r-TEG assay has not been assessed, but presumably would be effective for generating TEG tracings and values for maximum amplitude and angle in shorter periods of time than some traditional assays. [ABSTRACT FROM AUTHOR]

Although it has been shown that elevated white blood cell count (WBCc) on presentation is associated with an increased risk of cardiac mortality in patients with ST-segment elevation myocardial infarction (STEMI), the responsible mechanisms are unknown. We therefore sought to investigate whether elevated WBCc is associated with increased infarct size measured with cardiac magnetic resonance imaging 30 days after primary percutaneous coronary intervention in the Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction trial. INFUSE AMI randomized patients with STEMI and proximal or mideleft anterior descending coronary artery occlusion to bolus intracoronary abciximab versus no abciximab and to manual aspiration versus no aspiration. WBCc at hospital admission was available in 407 of 452 randomized patients. Patients were stratified according to tertiles of WBCc. At 30 days, a significant stepwise increase in infarct size (percentage of total left ventricular mass) was apparent across tertiles of increasing WBCc (median [interquartile range] for tertiles I vs II vs III = 11.2% [3.8% to 19.6%] vs 17.5% [0.5% to 22.9%] vs 19.1% [13.7 to 26.0], respectively, p <0.0001). Absolute infarct mass in grams and abnormal wall motion score were also significantly increased across tertiles of WBC. By multivariate linear regression analysis, WBCc was an independent predictor of infarct size along with intracoronary abciximab randomization, age, time from symptom onset to first device, proximal left anterior descending location, and baseline TIMI flow of 0/1. In conclusion, in patients with anterior wall STEMI, an elevated admission WBCc is a powerful independent predictor of infarct size measured with cardiac magnetic resonance imaging 30 days after primary percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Introduction In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI. Methods Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator' s discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end-point of this analysis was the 30-day incidence of ISAR-REACT-4 major bleeding. Results A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR- REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end-points or net clinical outcome (Pint > 0.56). Conclusions In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used. [ABSTRACT FROM AUTHOR]

We evaluated the effects of myocardial perfusion after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) on gender-based mortality rates. Research has demonstrated a gender-specific response of cardiomyocytes to ischemia and a potential increase in myocardial salvage in women compared with men. Myocardial blush grade (MBG), an angiographic surrogate of myocardial perfusion, is an independent predictor of early and late survival after AMI. Whether the incidence and prognosis of myocardial perfusion differs according to gender among patients with AMI undergoing PCI is unknown. MBG and short- and long-term mortality were evaluated in 1,301 patients (male = 935; female = 366) with AMI randomized to primary angioplasty ± abciximab versus stent ± abciximab. Following PCI, >96% of patients achieved final Thrombolysis In Myocardial Infarction 3 flow, of which MBG 2/3 was present in 58.3% of women versus 51.1% of men (p=0.02).Worse MBG was an independent predictor of mortality in women at 30 days (7.4% for MBG 0/1 vs 2.4% for MBG 2/3, p = 0.04) and at 1-year (11.0% for MBG 0/1 vs 3.4% for MBG 2/3, p = 0.01); however, MBG was not associated with differences in mortality for men. In conclusion, impaired myocardial perfusion following PCI for AMI, indicated by worse MBG, is an independent predictor of early and late mortality in women but not in men. These findings imply an enhanced survival benefit from restoring myocardial perfusion for women compared with men during primary angioplasty and may have clinical implications for interventional strategies in women. [ABSTRACT FROM AUTHOR]

Background--Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA. Methods and Results--We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60-0.80; P<0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63-0.81; P<0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70-2.59, P=0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results. Conclusions--For patients with acute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world. [ABSTRACT FROM AUTHOR]

There has been a tremendous boom in the arena of anticoagulant therapy recently. Although the indications for these agents reside in the noncritical care environment, over time, the impact of these agents have infiltrated the critical care environment particularly due to devastating complications with associated use. With so many newer agents on the market or coming down the pipeline, it is easy to become overwhelmed. It is important that the critical care practitioner does not ignore these agents but becomes familiar with them to better prepare for the management of patients on one or more anticoagulant agents in the intensive care unit. To equip the critical care practitioners with the knowledge about commonly used anticoagulants, we provide an extensive review of the pharmacology, indications, and adverse effects related to these agents as well as suggestions on preventing or managing complications. [ABSTRACT FROM AUTHOR]

Abstract: Background: Successful reperfusion of epicardial coronary arteries does not necessarily result in actual myocardial perfusion. Local intracoronary (IC) delivery of GP IIb/IIIa inhibitors (GPI) has been proposed to achieve further clinical efficacy when compared to standard intravenous (IV) administration. However clinical trials have shown conflicting results. The aim of the present study was to compare IC with IV abciximab administration on mortality and MACEs in patients with ACS undergoing PCI. Methods: We performed a meta-analysis of all available clinical trials comparing intracoronary versus intravenous abciximab administration. Results: At short-term analysis, incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.56; 95% CI 0.35–0.89; p=0.015). Interestingly, subgroup analysis showed that most benefit was coming from those studies with a main baseline LVEF<50% (OR=0.33 95% CI 0.18–0.59). Similarly, long-term incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.47; 95% CI 0.31–0.71; p<0.001), with most benefit coming from those studies enrolling patients with a main baseline EF<50% (OR=0.38 95% CI 0.23–0.63 p<0.001). In addition, long-term incidence of death was also lower in the IC group than in the IV group (OR=0.42; 95% CI 0.20–0.86; p=0.009). Conclusions: Our meta-analysis provides evidence of a net clinical benefit for intracoronary versus intravenous abciximab administration, with the highest benefit observed in high-risk ACS patients, such as those with reduced baseline LVEF. [Copyright &y& Elsevier]

Background: Administration of glycoprotein IIb/IIIa inhibitors is an effective adjunctive treatment strategy during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). Recent data suggest that an intracoronary administration of these drugs can increase the efficacy of PPCI. This study was done to find any potential difference in terms of efficacy of administering intracoronary Abciximab vs. intravenous Eptifibatide in primary PPCI. Methods: A total of 40 STEMI patients who underwent PPCI within 12 hours of symptom onset were randomized to either an intracoronary Abciximab (0.25 μg/kg) bolus or two boluses of intravenous Eptifibatide (0.180 μg/kg) each 10 minutes. The primary end points were enzymatic infarct size, myocardial reperfusion measured as ST-segment resolution (STR), and post-procedural thrombolysis in myocardial infarction (TIMI) grade flow of the infarct-related artery. The secondary end points were intra-procedural adverse effect (arrhythmia) and no-reflow phenomenon, in-hospital mortality, reinfarction, hemorrhage, and post-procedural global systolic function. Results: Post-procedural TIMI grade 3 flow was achieved in 95% and 90% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.61). The infarct size, as assessed by the area under the curve of creatine phosphokinase-MB in the first 48 hours after PPCI (μmol/L/hr ), was similar between the intracoronary Abciximab and intravenous Eptifibatide groups: 6591 (interquartile range [IQR], 3006.0 to 11112.0) versus 7,294 (IQR, 3795.5 to 11803.5); p value = 0.59. Complete STR was achieved in 55% and 45% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.87). No deaths, urgent revascularizations, reinfarctions, or TIMI major bleeding events were observed in either group. Conclusion: The intracoronary administration of Abciximab was not superior to the intravenous administration of Eptifibatide in the STEMI patients who underwent primary PCI. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to carry out a “real world” comparison of bivalirudin plus unfractionated heparin (UFH) versus abciximab plus UFH in patients undergoing primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). Methods: We included patients who had abciximab or bivalirudin during their PPCI in our unit between Sept 2009 and Nov 2011. Results: The study included 516 and 484 patients in the bivalirudin and abciximab group respectively. There were more women in the bivalirudin group (29% vs 20%, p 0.001), while cardiogenic shock (6.4% vs 10.1%, p 0.04) and thrombectomy device use (76.6% vs 82%, p 0.04) were lower in the bivalirudin group. The primary composite end point of 30-day mortality, 30-day definite stent thrombosis or non-CABG major bleeding was similar between the bivalirudin and abciximab groups (7.8% vs 9.5%, OR 0.8, 95% CI 0.5 to 1.2, p 0.4). There was also no difference in in-hospital mortality (4.1% vs 4.3%, p 0.9), 30-day mortality (5.2% vs 6.4%, p 0.5), 1-year mortality (9.1% vs 9.9%, p 0.7), 30-day stent thrombosis (1% vs 0.4%, p 0.5) and non-CABG bleeding (2.7 vs 3.7%, p 0.4) between the bivalirudin and abciximab group respectively. On Cox proportional hazard analysis after adjusting for all the co-variates, the use of bivalirudin was not a predictor of 30-day mortality (HR 1.13, 95% CI 0.7–1.9, p 0.7). Conclusion: In this “real-world” observational study, there was no significant difference in the clinical outcome of PPCI for patients who had abciximab or bivalirudin after initial pre-treatment with UFH. [Copyright &y& Elsevier]