UMLS:C0151744 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formation of platelet-rich thrombus superimposed on ruptured atherosclerotic plaque has been implicated in the development of myocardial ischemia and its clinical manifestations. The platelet glycoprotein (GP) IIb-IIIa receptor is the final common pathway leading to platelet aggregation and thrombus formation. GP IIb-IIIa is therefore a logical therapeutic target for management of acute ischemic coronary syndromes and prevention of the ischemic complications of percutaneous coronary procedures. Of the pharmaceutical agents under development, the chimeric monoclonal antibody abciximab (ReoPro) and the cyclic peptide eptifibatide (INTEGRILIN) are the most studied. IMPACT II (Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis), the phase III evaluation of eptifibatide in patients undergoing percutaneous coronary intervention, demonstrated the effectiveness and safety of this GP IIb-IIIa receptor inhibitor in reducing the acute adverse outcomes of invasive management of ischemic heart disease. GP IIb-IIIa receptor blockade provides an effective strategy for prevention of ischemic complications related to angioplasty in patients with coronary artery disease.
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PMID:Impact of eptifibatide on early ischemic events in acute ischemic coronary syndromes: a review of the IMPACT II trial. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis. 929 Dec 42

The mechanisms of action of currently available and newer antiplatelet agents and evidence of the efficacy of antiplatelet agents for primary and secondary prevention of coronary artery disease are reviewed. Available data do not support the widespread use of aspirin for primary prevention of cardiovascular disease. Patients over the age of 50 years with at least one additional risk factor for coronary artery disease may benefit, although possibly at an increased risk of hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular disease in patients with stable or unstable angina, clinical or laboratory evidence of coronary artery disease, history of myocardial infarction, or history of stroke or transient ischemic attack. There are no data supporting a role for dipyridamole for primary or secondary prevention of ischemic heart disease. Abciximab has been shown to reduce the risk of cardiovascular complications at 30 days after percutaneous transluminal coronary angioplasty in patients with refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded promising results. Ticlopidine may be used for secondary prevention of cardiovascular disease in patients with unstable angina who are allergic to or intolerant of aspirin. Clopidogrel has been shown to be safe and effective for secondary prevention of vascular events. Aspirin has a role in secondary prevention of coronary artery disease; among patients who are allergic to or intolerant of aspirin, ticlopidine has a role in patients with unstable angina and clopidogrel has a potential role in patients with ischemic heart or vascular disease.
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PMID:Antiplatelet therapy in coronary artery disease: review and update of efficacy studies. 978 97

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.
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PMID:The effects of antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia in rats. 1037 Apr

Large clinical studies have demonstrated an unequivocal clinical benefit of antithrombotic therapy with inhibitors of the platelet surface-membrane glycoprotein (GP) IIb-IIIa receptor in a broad range of patients with ischemic heart disease. Potent antiplatelet effects of these agents, however, may increase the risk of bleeding complications, as occurred in the first large evaluation of this therapy, the Evaluation of c7E3 for Prevention of Ischemic Complications (EPIC) trial with abciximab (c7E3 Fab; ReoPro((R)); Centocor, Malvern, Pa). Although the incidence of bleeding events in subsequent studies has been reduced through the use of a low-dose, weight-adjusted heparin regimen and early removal of vascular sheaths in patients who have undergone percutaneous coronary interventions, hemorrhage continues to be the most common complication of GP IIb-IIIa inhibitor therapy. This review summarizes current experience related to bleeding complications with various GP IIb-IIIa inhibitors and suggests strategies for improved management of bleeding in patients receiving these agents.
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PMID:Bleeding complications of glycoprotein IIb-IIIa receptor inhibitors. 1050 34

Platelet-mediated coronary thrombosis is the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute ischemic complications of percutaneous coronary intervention (PCI). The final common pathway of platelet aggregation that leads to thrombotic occlusion of coronary arteries involves cross-linking of receptor glycoprotein (GP) IIb-IIIa on adjacent platelets by adhesive plasma proteins, primarily fibrinogen. Clinical trials of several GP IIb-IIIa inhibitors have demonstrated an unequivocal clinical benefit of this potent antithrombotic therapy in patients with ACS as well as in those undergoing PCI. Nevertheless, a significant number of patients with ischemic heart disease may still be expected to require elective or emergency coronary artery bypass graft (CABG) after treatment with GP IIb-IIIa inhibitors. In the emergency CABG setting, complications and platelet blockade with GP IIb-IIIa inhibitors may further enhance the already heightened risk of bleeding as compared with elective procedures. This issue became apparent in the first large clinical trial of the GP IIb-IIIa inhibitor abciximab (c7E3 Fab, ReoPro((R)); Centocor, Malvern, Pa, and Eli Lilly and Co, Indianapolis, Ind) in patients undergoing high-risk PCI. In this study, mortality rates and bleeding complications were increased among patients undergoing emergency CABG after treatment with a bolus plus infusion of abciximab. Subsequent clinical experience also suggests that the potential for bleeding complications related to emergency CABG may be increased in patients treated with abciximab, particularly if the drug is discontinued within 6 hours of the operation. Higher bleeding risk with abciximab is a result of its prolonged antiplatelet effect, which is in contrast to the readily reversible platelet blockade provided by more recently developed small-molecule GP IIb-IIIa inhibitors such as the peptide eptifibatide (Integrilin((R)); COR Therapeutics, South San Francisco, Calif, and Key Pharmaceuticals, Kenilworth, NJ) and the nonpeptide tirofiban HCl (MK-383, Aggrastat((R)); Merck & Co, Whitehouse Station, NJ). Therefore, among patients requiring CABG after treatment with GP IIb-IIIa inhibitors, eptifibatide and tirofiban may be associated with fewer bleeding episodes than is abciximab. With recent approval of eptifibatide for patients with ACS and those scheduled for PCI and of tirofiban for patients with ACS, the number of patients receiving GP IIb-IIIa inhibitor therapy who subsequently undergo CABG is expected to increase significantly. Strategies for improved management of bleeding complications in these patients, including the choice of a GP IIb-IIIa inhibitor, are clearly needed and are discussed in detail.
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PMID:Safety of glycoprotein IIb-IIIa inhibitors: A heart surgeon's perspective. 1050 36

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as myocardial injury, due in large part to endothelial dysfunction, upregulation of cell adhesion molecules and subsequent neutrophil induced cardiac injury. We studied the effects of abciximab (ReoPro), an anti-IIb/IIIa antibody, which has been shown to attenuate platelet interactions, in a neutrophil-platelet mediated isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of abciximab (6.5 micrograms/kg) 10 min prior to the perfusion of the PMN + platelet perfused I/R heart improved post-reperfusion coronary flow and preserved post-reperfusion left ventricular developed pressure (LVDP) and +dP/dt max as indices of cardiac contractile function. Abciximab-treated hearts reperfused in the presence of PMNs and platelets preserved all indices of cardiac contractile function. I/R heart perfused with PMNs and platelets produced a profound injury to the hearts which was attenuated with the treatment of abciximab. In addition, abciximab significantly reduced PMN accumulation in the ischemic myocardium from 38 +/- 1 PMNs/mm2 in untreated hearts to 7 +/- 1 in rats given abciximab. Similar results were obtained with PMN perfused I/R rat hearts without platelets. These results provide evidence that abciximab is a potent and effective cardioprotective agent that inhibits leukocyte-endothelial cell interactions as well as platelet-endothelial cell interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion. Therefore, IIb/IIIa may be important in attenuating both platelet and neutrophil-mediated myocardial dysfunction.
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PMID:Cardioprotective effects of abciximab (ReoPro) in an isolated perfused rat heart model of ischemia and reperfusion. 1059 51

During the last 10 years a new group of drugs was developed--platelet glycoprotein IIb/IIIa blockers that is nowadays largely and efficiently used as for the prevention of percutaneous coronary intervention complications as well as in the treatment of acute coronary syndromes. In the period February-June 2000--19 patients (18 males, 1 female, of average age 53.3 years) were administered Abciximab in the bolus dose of 10 mg immediately before the intervention and afterwards 10 mg by 12-hour infusion. All patients received aspirin and ticlopidine hydrochloride if the stent was introduced and heparin by the standard protocol. Elective intervention was done in 17 patients (non-Q infarction in 3 patients, unstable angina pectoris in 5 patients, postinfarction angina pectoris in 2 patients, acute myocardial infarction at least 1 month before the intervention in 6 patients and 1 patient with myocardiopathy) and in 2 patients the intervention was performed during the myocardial infarction. In 15 patients (79%) intracoronary stent was introduced and in 5 patients (21%) the intervention was performed on 2 arteries. Maximal immediate effect of the dilatation was achieved in 18 patients (94.7%). In the first 60 days of the follow-up 1 patient (5%) died of some other disease, and in no patients symptomatic myocardial ischemia was found. No adverse effects were observed.
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PMID:[Clinical study of administration of abciximab--a monoclonal antibody to platelet glycoprotein IIb/IIIa in percutaneous intracoronary interventions]. 1176 14

First Russian glycoprotein (GP) IIb-IIIa antagonist, preparation Monafram, is the F(ab')2 fragment of anti-GP IIb-IIIa monoclonal antibody FRaMon. In in vitro experiments it was shown that Monafram blocked platelet aggregation induced by ADP and thrombin; reduced secretion from platelet granules; and due to simultaneous interaction with two GP IIb-IIIa molecules almost irreversibly bound to platelet surface. Monafram clinical trials were performed in healthy volunteers (n = 10) and in patients with ischemic heart disease undergoing high risk coronary angioplasty (n = 153). Monafram intravenous bolus administration at 0.25 mg/kg decreased ADP-induced platelet aggregation by more than 90, 80, 60 and 30% at 1, 12, 24 and 72 h after injection, respectively. No significant differences were detected between antiaggregatory effects of Monafram and ReoPro introduced at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min. Durable inhibition of aggregation after Monafram administration was mediated by platelet-bound preparation--free Monafram was cleared from plasma within 12 h, while platelet-bound preparation occupied more than 90, 70-80 and 40-50% of GP IIb-IIIa at 1, 12-24 and 72 h after injection, respectively. Major bleedings and allergic reactions were detected in none of patients, deep thrombocytopenia--in one patient and antibodies against Monafram--in 5% of patients. Within one month after coronary angioplasty Monafram decreased the number of end points (fatal and nonfatal myocardial infarction and angina recurrence) from 11.4 to 3.3%.
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PMID:[Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram]. 1534 Oct 84

Large clinical trials have demonstrated the clinical effectiveness of therapy with inhibitors of the platelet surface-membrane glycoprotein IIb-IIIa receptor in a broad range of patients with ischemic heart disease. Abciximab, a platelet glycoprotein IIb-IIIa receptor blocker, is associated with improved long-term prognosis in patients who require angioplasty and stent placement. Severe bleeding from abciximab use is an uncommon event. We describe a patient with severe pulmonary hemorrhage after treatment with abciximab, and discuss predisposing factors and protamine infusion in this potentially fatal complication.
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PMID:[Pulmonary hemorrhage after abciximab. Risk factors and the role of protamine]. 1584 42

Despite improvements in the safety and efficacy of percutaneous transluminal coronary angioplasty (PTCA), ischaemic procedural complications continue to occur in up to 10 to 20% of patients. As the pivotal role of platelets in the formation of arterial thrombosis following coronary intervention was elucidated, it became apparent that an inhibitor of platelet aggregation might reduce the rate of acute ischaemic complications and restenosis following PTCA. Attention has focused on the platelet glycoprotein (GP) IIb/IIIa integrin, a receptor that mediates the final common pathway of platelet aggregation. A murine monoclonal antibody that binds to and blocks the IIb/IIIa receptor inhibits the binding of fibrinogen to platelets and thus inhibits platelet aggregation. To minimise the potential for human anti-murine antibody responses, this antibody was modified to a chimaeric antibody fragment, abciximab (c7E3 Fab), composed of an antigen-binding fragment with human constant regions and mouse variable regions. Abciximab was recently approved by the US Food and Drug Administration for clinical use. The efficacy and safety of abciximab have been demonstrated in 3 recently completed phase III clinical trials which enrolled a total of 6156 patients undergoing coronary angioplasty. The study results have unequivocally demonstrated that platelet GP IIb/IIIa receptor inhibition with abciximab during coronary intervention markedly reduces the incidence of postprocedural ischaemic events. In the EPIC trial, a dose-related effect of abciximab in the prevention of ischaemic complications was observed, with a significant 35% reduction in the incidence of the composite end-point among the patients receiving the abciximab bolus and 12-hour infusion compared with the double-placebo group. In the EPILOG trial, patients treated with abciximab bolus and 12-hour infusion with low-dose heparin had a significant 56% reduction in the incidence of the composite end-point at 30 days. In the CAPTURE study, the primary end-point was reduced at 30 days by 29% with abciximab therapy. The treatment effect observed at 30 days for reduction in acute ischaemic complication was maintained throughout the 6-month follow-up period. Although abciximab therapy may carry an increased risk of bleeding complications, such excess haemorrhagic risk can be eliminated by strategies such as reduction of adjunctive heparin dosage, early sheath removal, and conservative management of the vascular access site. The role of platelet glycoprotein IIb/IIIa receptor inhibition in the acute coronary syndromes of unstable angina and acute myocardial infarction treated by percutaneous intervention or with thrombolytic therapy is an exciting new frontier in ischaemic heart disease and is currently under investigation. The complementarity of these agents with new devices for coronary revascularisation, such as stents, is also the subject of important new trials. Finally, future studies will also focus on the role of long term GP IIb/IIIa inhibition with the new generation of orally active agents.
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PMID:Clinical experience with abciximab during coronary revascularisation: an overview. 1802 May 84

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