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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycoprotein IIb/IIIa receptor antagonists are effective in decreasing cardiac events in patients with acute coronary syndromes. Abciximab reduces cardiac morbidity in patients receiving coronary stents. We sought to evaluate the use of tirofiban infusion in patients receiving intracoronary stents. We created a prospective registry of 50 consecutive patients in a single catheterization lab receiving a single vial of tirofiban (12.5 mg) and stenting. Successful stent deployment with a 30-day follow-up occurred in all patients. Clinical endpoints included death (0%), procedural infarct (4%), urgent revascularization (0%), stroke (0%), bleeding complication (4%), and vascular injury (0%). Tirofiban appeared to be a safe adjunctive therapy to coronary stenting.
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PMID:Tirofiban and intracoronary stenting: evaluation of a new pharmacologic regimen. 1074 71

Inhibition of platelet aggregation with aspirin and anticoagulation with unfractionated heparin can be considered the gold standard treatment of patients with acute coronary syndromes. Replacement of unfractionated heparins by low-molecular weight heparins seem to further improve the cardiovascular risk. Additional treatment with glycoprotein IIb/IIIa receptor blockers led to a further reduction of the clinical event rate, especially in patients undergoing coronary interventions during an acute coronary syndrome (more than 30% relative risk reduction). However, the latter substances did only lead to marginal improvements in the setting of a conservative stabilization of patients with acute coronary syndrome (7% relative risk reduction). On the contrary, the initial treatment with clopidogrel in addition to aspirin and anticoagulation led to a 20% relative risk reduction for an endpoint of death, myocardial infarction and stroke in the CURE trial. The treatment with aspirin, clopidogrel (including loading-dose) for a treatment period of 3-12 months and anticoagulation for 2 days can be considered the new standard of treatment in patients with acute coronary syndromes (unstable angina, non-ST-segment elevation, myocardial infarction). Glycoprotein IIb/IIIa receptor blockers should be used especially during coronary interventions. Antianginal treatment should include nitrates and betablockers. A treatment with statins and ACE-inhibitors should be initiated in the early course of acute coronary syndrome for plaque stabilization.
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PMID:[Modern therapy in acute coronary syndrome]. 1197 80

Platelets play an important role in the pathophysiology of acute myocardial infarction, unstable angina, and ischemic stroke. The expression of the glycoprotein IIb/IIIa (alphaIIb/beta3 integrin) receptor on the surface of activated platelets constitutes the common pathway for platelet aggregation. Glycoprotein IIb/IIIa has low affinity for its soluble ligands (fibrinogen and von Willebrand factor) in resting platelets. In the setting of vascular injury, platelet activation occurs after binding of the glycoprotein Ib-IX-V receptor to von Willebrand factor in the extracellular matrix (at high shear rate) and binding of soluble agonists to specific platelet membrane receptors. The ensuing inside-out signaling increases several-fold the affinity and avidity of alphaIIb/beta3 for its ligands. High affinity ligand binding to alphaIIb/beta3 triggers outside-in signaling, causing microskeletal contraction and platelet retraction. The signaling pathways for inside-out and outside-in signaling are incompletely understood. Glycoprotein IIb/IIIa antagonists were developed under the premise that these agents would abrogate platelet aggregation while preserving platelet monolayer deposition at sites of injury. A number of parenteral and oral agents have been developed and evaluated in clinical trials. Three of them are approved in the United States and other countries: abciximab (ReoPro; the Fab fragment of a chimeric human-mouse antibody), eptifibatide (Integrelin; a cyclic heptapeptide), and tirofiban (Aggrastat; a tyrosine-derived nonpeptide molecule). The greatest clinical impact of these parenteral agents (used in conjunction with aspirin and heparin) has been in the prevention of ischemic complications after percutaneous coronary intervention. In contrast, oral agents have yielded disappointing results in the secondary prevention of acute coronary syndromes, and none of them are approved at present. Eptifibatide and tirofiban are specific for alphaIIb/beta3, whereas abciximab also exhibits cross-reactivity with the alphavbeta3 and alphaMbeta2 integrins. Although alphaIIb/beta3 is unique to platelets and megakaryocytes, alphavbeta3 is more widely distributed and mediates several functions, including endothelial cell migration, monocyte adhesion, angiogenesis, and inhibition of apoptosis. alphaMbeta2 mediates leukocyte-platelet interactions. In the percutaneous coronary intervention trials, abciximab has been more efficacious than the other parenteral agents, perhaps because of cross-reactivity with these other integrins, the pharmacodynamic profile of abciximab, or other effects. Other documented effects of abciximab include acute dethrombosis, reduction of thrombin generation, and improved flow in the coronary microcirculation after percutaneous coronary intervention. Abciximab is presently under evaluation in the treatment of acute ischemic stroke. Promising data have been obtained in experimental models of tumor angiogenesis and sickle cell anemia.
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PMID:Platelet glycoprotein IIb/IIIa antagonists: lessons learned from clinical trials and future directions. 1200 56

Early complications may hamper efforts to hasten discharge after primary percutaneous coronary intervention (PCI) for myocardial infarction (MI). Glycoprotein IIb/IIIa inhibitors, by reducing early recurrent ischemia, may aid in these efforts. We examined whether adjunctive abciximab could accelerate discharge and reduce costs within a trial of primary PCI after acute MI. The CADILLAC trial randomized 2,082 patients with MI to 1 of 4 reperfusion strategies in a 2 x 2 factorial design: angioplasty, angioplasty with abciximab, stent implantation, or stenting with abciximab. Patients randomized to abciximab had postprocedural heparin withheld, and discharge scheduled for days 1.5 to 2 (low-risk patients) or days 2 to 3 (high-risk patients) after MI if they were stable. Other patients were discharged at the physician's discretion. Abciximab treatment was associated with significant reductions in the primary end points of in-hospital death, reinfarction, ischemic target vessel revascularization (TVR), or disabling stroke (5.6% vs 2.7%, p = 0.003)--largely reflecting reduced ischemic TVR (3.8% vs 1.4%, p = 0.002)--and in early subacute thrombosis (1.3% vs 0.2%, p = 0.01). Hospitalization was significantly shorter in abciximab-treated patients (median 3.1 vs 3.5 days, p <0.001), but total in-hospital costs did not differ significantly (13,413 +/- 5,309 US dollars vs 13,000 +/- 6,006 US dollars, p = 0.13). Rates of the composite end point did not differ significantly during the week after discharge (0.8% vs 0.2%, p = 0.10), nor did component event rates. Abciximab during primary PCI is associated with fewer early adverse outcomes, likely contributing to offset its cost. Hospitalizations after primary PCI are so short, however, that efforts to accelerate discharge with abciximab appear unfeasible, and overall costs remain unchanged.
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PMID:Feasibility and implications of an early discharge strategy after percutaneous intervention with abciximab in acute myocardial infarction (the CADILLAC Trial). 1451 75

Haemostasis is a finely balanced and complex process ideally initiated only in response to disruption of the vascular endothelium as a means of preventing loss of blood from an injured vessel. Deviations from the ideal can lead to serious disease. Firstly, thrombosis, which arises as a consequence of inappropriate platelet-platelet interactions at a region of vessel damaged by atherosclerosis, can lead to occlusion of the affected vessel as in myocardial infarction or stroke. Secondly, loss of the ability of platelets to form aggregates leads to Glanzmann's thrombasthenia (GT) with a tendency to bleed for prolonged periods following injury. Glycoprotein IIb/IIIa (GPIIb/IIIa) plays a major role in the regulation of platelet adhesion and aggregation during haemostasis. Upon platelet activation by an agonist a signalling process is initiated, termed "inside-out" signalling, which gives rise to conformational changes within GPIIb/IIIa. These conformational changes increase the affinity of the receptor for its primary ligand, fibrinogen. Bound fibrinogen then acts as a bridging molecule facilitating the interaction of adjacent platelets. Upon fibrinogen binding GPIIb/IIIa undergoes further conformational changes and through a process termed "outside-in" signalling the receptor signals in to the platelet ultimately resulting in acceleration of the aggregation process. Qualitative or quantitative abnormalities in GPIIb/IIIa give rise to GT, a recessive bleeding disorder, and analysis of affected individuals has provided invaluable insights into the structure/function relationship of this receptor. Due to its critical role in mediating platelet aggregate formation GPIIb/IIIa has become a primary target for the development of antithrombotic agents.
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PMID:The role of the platelet glycoprotein IIb/IIIa in thrombosis and haemostasis. 1513 55

Platelet activation and aggregation have become increasingly recognized as the primary processes involved in the cascade that leads to thrombus formation in atherosclerotic vascular disease. Glycoprotein IIb/IIIa receptor inhibitors (GPI) favorably impact thrombus formation and distal embolization by inhibiting the final common pathway of platelet aggregation. Glycoprotein IIb/IIIa inhibitors have been used effectively in a wide variety of clinical scenarios including unstable angina, non-ST segment elevation myocardial infarction, ST segment elevation myocardial infarction, and low and high risk percutaneous coronary interventions with and without intracoronary stenting, however there is limited data regarding the use of these potent antiplatelet agents in the setting of extracardiac vascular disease. This article will review the non-cardiac applications of glycoprotein IIb/IIIa inhibitors in the setting of acute ischemic stroke, carotid and vertebral angioplasty and stenting, acute critical limb ischemia, and percutaneous interventions in peripheral arterial occlusive disease.
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PMID:Noncardiac applications of glycoprotein IIb/IIIa inhibitors. 1527 67

Although elevated systemic blood pressure (BP) results in high intravascular pressure, the main complications of hypertension are related to thrombosis rather than haemorrhage. It therefore seemed plausible that use of antithrombotic therapy may be useful in preventing thrombosis-related complications of elevated BP. The objectives were to conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with BP, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment. A systematic review of randomised studies in patients with elevated BP was performed. Studies were included if they were >3 months in duration and compared antithrombotic therapy with control or other active treatment. One meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated BP reported an absolute reduction in vascular events of 4.1% as compared to placebo. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated BP and no prior cardiovascular disease. Based on one large trial, ASA taken for 5 years reduced myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), increased major haemorrhage (ARI, 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In two small trials, warfarin alone or in combination with ASA did not reduce stroke or coronary events. Glycoprotein IIb/IIIa inhibitors as well as ticlopidine and clopidogrel have not been sufficiently evaluated in patients with elevated BP. To conclude for primary prevention in patients with elevated BP, antiplatelet therapy with ASA cannot be recommended since the magnitude of benefit, a reduction in myocardial infarction, is negated by a harm of similar magnitude, an increase in major haemorrhage. For secondary prevention in patients with elevated BP, antiplatelet therapy is recommended because the magnitude of the absolute benefit is many times greater. Warfarin therapy alone or in combination with aspirin in patients with elevated BP cannot be recommended because of lack of demonstrated benefit. Further trials of antithrombotic therapy are required in patients with elevated BP.
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PMID:Antithrombotic therapy in hypertension: a Cochrane Systematic review. 1638 20

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death. We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting. A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%). Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes. The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.
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PMID:An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards. 1717 71

Despite aspirin's established role in the treatment of atherosclerotic vascular disease, considerable controversy exists regarding its most effective dosing strategy. In a retrospective observational study, we examined the relation between prescribed aspirin dose (<162 mg vs > or =162 mg/day aspirin) and clinical outcome in 4,589 placebo-treated patients enrolled in the Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial over a median follow-up of 366 days. Standard Cox regression analysis was employed because propensity analysis was not feasible. Compared with lower aspirin doses, higher doses were associated with lower unadjusted all-cause mortality (2.9 vs 1.6%, respectively; log rank chi-square 8.6, p = 0.0034). Higher aspirin dose remained independently predictive of lower all-cause mortality in a multivariable Cox proportional hazards model (hazard ratio 0.64, 95% confidence interval 0.42 to 0.97, p = 0.037). However, there was no significant difference in the incidence of the composite endpoint death, nonfatal myocardial infarction, or nonfatal stroke (6.1% vs 6.2%, p = 0.74). Higher aspirin dose was a significant independent predictor of any (hazard ratio 1.32, 95% confidence interval 1.12 to 1.55, p = 0.001) but not serious bleeding. In conclusion, our findings suggest that aspirin doses of > or =162 mg/day may be more beneficial than those <162 mg/day at preventing death.
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PMID:Relation between aspirin dose, all-cause mortality, and bleeding in patients with recent cerebrovascular or coronary ischemic events (from the BRAVO Trial). 1899 42

Acute ischemic stroke (AIS) is a common cause of morbidity and mortality worldwide. Thrombolytic therapy with tissue plasminogen activator, the only approved treatment for AIS, is received by less than 2% of patients. Moreover, there is a slight increase in hemorrhagic complications with thrombolysis. Therefore, there is a need for newer therapeutic modalities in AIS, which could be used in window periods beyond 3-6 h after stroke onset with fewer hemorrhagic complications. Glycoprotein IIb/IIIa inhibitors (GPI), after their initial success in patients with acute coronary syndromes, promised much in patients with AIS over the past decade or so. However, their exact role in patients with AIS, including the window periods and type of strokes, and the risk of symptomatic or asymptomatic hemorrhage are unclear at the moment. The current review focuses on the literature concerning the use of GPI in AIS and looks at the available evidence regarding their use. Abciximab thought to be safe and effective in initial case series and early trials, has not been shown to improve outcomes in AIS, and is associated with higher rates of hemorrhage. Tirofiban appears to be safe and effective in initial trials and there is a need to conduct further trials to establish its role in AIS.
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PMID:Platelet glycoprotein IIb/IIIa inhibitors in acute ischemic stroke. 1912 33


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