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

Stroke is a major public health problem in the United States and the development of novel therapeutic strategies is an important research priority. Advances in this field are proceeding on several fronts, including the use of next-generation plasminogen activators and glycoprotein IIb/ IIIa inhibitors, refined patient selection with advanced magnetic resonance imaging sequences, endovascular approaches to thrombolysis and thrombectomy, and adjuvant use of ultrasound. There remains no proven therapy for intracerebral hemorrhage, but early results with recombinant activated factor VII look very promising. It is hoped that in the near future, physicians managing patients with acute neurological events will have a robust armamentarium of therapies to bring to bear on both ischemic and hemorrhagic vascular disease.
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PMID:Emerging therapies for acute ischemic stroke. 1751 6

Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than with either aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox) were carried out in Europe and North America. Considering potential inter-racial differences in drug response, we conducted a small randomized study in healthy Japanese volunteers to compare antiplatelet regimens with regard to the changes in the platelet biomarkers. Thirty healthy volunteers (18-40 years old, 15 male and 15 female) of Japanese descent were randomized to Aggrenox (n = 17) or aspirin 81 mg (n = 13 volunteers) for 30 days. Platelet function was assessed at baseline, and on days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer. Both Aggrenox and aspirin provided sustained platelet inhibition at Day 15 and Day 30. Therapy with Aggrenox, however, was associated with more prominent and significant inhibition of collagen-induced aggregation (p = 0.08, Day 15), as well as prolongation of the closure time (p = 0.001, Day 30); diminished expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.02, Day 30), glycoprotein IIb (GPIIb) antigen (p = 0.001 and 0.024 for Day 15 and Day 30), and GPIIb/IIIa activity by PAC-1 antibody (p = 0.014 and 0.03), CD62 (P-selectin) (p = 0.03 for Day 15 and Day 30), as well as inhibition of protease activated receptors (PAR-1) associated with intact WEDE-15 (p = 0.002 and 0.003) and SPAN-12 (p = 0.002 and 0.04) thrombin receptors when compared with aspirin. The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. A larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.
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PMID:Magnitude and time course of platelet inhibition with extended release dipyridamole with or without aspirin in healthy Japanese volunteers. The AGgrenox versus Aspirin Therapy Evaluation (AGATE-Japan). 1821 42

Drugs that inhibit platelet function are widely used to decrease the risk of occlusive arterial events in patients with atherosclerosis. There are three families of anti-platelet agents with proven clinical efficacy: (1) cyclo-oxygenase inhibitors, such as aspirin; (2) adenosine diphosphate receptor antagonists, such as the thienopyridine compounds ticlopidine and clopidogrel; and (3) glycoprotein IIb/IIIa antagonists. All these drugs are used during coronary interventions and in the medical management of acute coronary syndromes, while only aspirin and thienopyridine compounds are used in the long-term prevention of cardiovascular and cerebrovascular events in patients at risk. Despite the good risk-to-benefit ratio of anti-platelet agents, the risk of severe bleeding complications, including cerebral haemorrhage, is slightly increased, albeit to a much lesser extent than that associated with the use of other antithrombotic drugs, such as anticoagulants or thromobolytic agents. In addition, it must be noted that the increased incidence of haemorrhagic stroke is usually outweighed by a significant decrease in the incidence of ischaemic strokes. The combination of aspirin and vitamin K antagonists may be associated with the heightened risk of cerebral haemorrhage, compared to treatment with either drug alone.
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PMID:Haemorrhagic stroke during anti-platelet therapy. 1828 11

Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses.
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PMID:Genetic polymorphisms for the study of multifactorial stroke. 1842 1

Rapid arterial rethrombosis is associated with high-grade residual stenosis and usually occurs at the site of the initial occlusion, resulting in reocclusion of the recanalized artery. Platelets may play an active role in such rethrombosis after thrombolytic-induced clot lysis. Given that glycoprotein IIb/IIIa receptor blockers, like tirofiban, prevent thrombus formation by inhibiting the final common pathway of platelet aggregation, they may be helpful for treating rethrombosis after thrombolysis. A 64-year-old man presented with an acute ischemic stroke due to internal carotid artery (ICA) occlusion. The ICA was recanalized by intravenous thrombolysis but reoccluded shortly after recanalization. The reoccluded ICA was successfully recanalized using intra-arterial tirofiban. A carotid stent was subsequently inserted to relieve severe stenosis and to prevent recurrent stroke. Here, we report a case of rescue treatment of a successfully recanalized ICA by intra- arterial tirofiban. We suggest that rescue use of intra-arterial tirofiban may be effective and safe, especially in hemorrhage prone situations, due to the relatively lower dose of tirofiban compared with intravenous doses.
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PMID:Rescue treatment with intra-arterial tirofiban infusion and emergent carotid stenting. 1897 9

The incidence of thrombocytopenia after hospital admission, patient and treatment characteristics, and outcomes in patients enrolled in the prospective multinational GRACE were examined. Heparin (unfractionated or low molecular weight) and glycoprotein IIb/IIIa-inhibition can be associated with immune-mediated thrombocytopenia of clinical importance. The prevalence of thrombocytopenia in patients with acute coronary syndromes (ACSs) in general and specifically related to these therapies and associated outcomes have been studied little outside of clinical trials. Patients with an ACS were stratified into 4 groups of those with heparin-induced thrombocytopenia (HIT), those with glycoprotein IIb/IIIa-associated thrombocytopenia (GAT), those with other thrombocytopenia (not diagnosed as HIT or associated with glycoprotein inhibitors), and those with no thrombocytopenia. From June 2000 to September 2007, a total of 52,647 patients with an ACS and information for platelet count were enrolled in GRACE. Of these, 152 (0.3%) were reported to develop HIT, 324 (0.6%) developed GAT, and 368 (0.7%) developed other thrombocytopenia. Patients with HIT, GAT, or other thrombocytopenia were significantly more likely to die in the hospital versus those without these diseases (adjusted odds ratio [OR] 1.94, 95% confidence interval [CI] 1.07 to 3.53; adjusted OR 3.45, 95% CI 2.35 to 5.05; and adjusted OR 2.83, 95% CI 1.97 to 4.06, respectively). They were also more likely to experience major bleeding, (re)infarction, or stroke. In conclusion, in this large multinational registry, 1.6% of patients with ACS were reported to develop thrombocytopenia, with only 0.3% being HIT. Regardless of whether patients had clinically recognized HIT, GAT, or other thrombocytopenia, all 3 groups had significantly higher rates of major bleeding, recurrent infarction, stroke, and death.
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PMID:Thrombocytopenia in patients with an acute coronary syndrome (from the Global Registry of Acute Coronary Events [GRACE]). 1912 32

We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes and the CT when blood was perfused through cartridges coated with collagen plus ADP (CADP-CT). The ASA non-responsive cohort had significantly increased whole blood platelet counts (p = 0.03) and plasma von Willebrand Factor antigen levels (p < 0.001), which likely contributes to resistance to the inhibitory effects of ASA in the PFA-100.
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PMID:Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease. 1913 98

Recent studies have documented that use of "facilitated" percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) may be harmful. In-hospital outcomes in 1,553 consecutive patients with STEMI without cardiogenic shock who underwent PCI at a single tertiary center within 6 hours of presentation were analyzed. The study group included 767 patients who underwent primary PCI who initially presented to the tertiary center and were triaged for emergent PCI and 786 patients who underwent facilitated PCI who were pretreated at a community hospital with a glycoprotein IIb/IIIa platelet inhibitor and/or intravenous thrombolytic therapy before transfer for catheter-based therapy. Compared with patients who underwent primary PCI, the facilitated PCI group had longer door-to-balloon times (162 +/- 57 vs 113 +/- 61 minutes), higher baseline infarct-vessel TIMI 3 flow rates (52.8% vs 25.4%; p <0.001), and no increase in major adverse in-hospital outcomes. In patients treated with door-to-balloon times >90 and < or =150 minutes, patients who underwent facilitated PCI had fewer composite major adverse clinical events (combined mortality, recurrent myocardial infarction, emergent repeated PCI, hemorrhagic and nonhemorrhagic stroke, and nonintracranial TIMI major bleeding) compared with patients who underwent primary PCI (relative risk 0.50, 95% confidence interval 0.26 to 0.96, p = 0.034). In conclusion, facilitated PCI can be safely used to increase pharmacologic reperfusion before catheter-based therapy in patients with STEMI without an increase in clinical hazard and with fewer major adverse clinical events in patients treated with door-to-balloon times >90 and < or =150 minutes.
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PMID:Comparison of outcomes and safety of "facilitated" versus primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. 1916 82

Bivalirudin has been associated with decreased bleeding, with similar rates of ischemia in patients with stable angina, unstable angina, non-ST elevation myocardial infarction and elective percutaneous coronary intervention (PCI). The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial tested whether with primary PCI, bivalirudin--compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor--reduced bleeding and net clinical benefit (bleeding, death, reinfarction, target-vessel revascularization for ischemia or stroke). Bivalirudin reduced major bleeding by 40% (4.9 vs 8.3%; risk ratio [RR]: 0.60; 95% confidence interval [CI]: 0.46-0.77; p < 0.0001) as compared with unfractionated heparin and a IIb/IIIa antagonist. Net adverse clinical events were reduced (9.2 vs 12.1%; RR: 0.76: 95% CI: 0.63-0.92; p = 0.005). Cardiac death and total death at 30 days were reduced with bivalirudin (1.8 vs 2.9%; p = 0.03) and (2.1 vs 3.1%; p = 0.047), and at 12 months (2.1 vs 3.8%; p < 0.005) and (3.4 vs 4.8%; p = 0.029), respectively. Bivalirudin reduced bleeding and net adverse clinical events as well as mortality compared with unfractionated heparin and a glycoprotein IIb/IIIa inhibitor. Bivalirudin is an attractive antithrombotic choice in patients undergoing primary PCI.
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PMID:HORIZONS trial: a step forward for primary percutaneous coronary intervention. 1921 Feb 8

Several clinical trials have shown that antagonists of the glycoprotein IIb/IIIa receptor decreased the incidence of death, nonfatal myocardial infarction, and the need for urgent revascularization when administered immediately before or during the 24- to 48-hour period after percutaneous coronary intervention (PCI). However, these agents increased the risk of thrombocytopenia and periprocedural bleeding complications. Therefore, the relation between periprocedural bleeding complications during PCI and long-term outcome was assessed in 6,995 patients in the EXCITE trial. Periprocedural bleeding was classified as none, mild, moderate, and severe. Measured outcomes included the incidence of all-cause mortality or the composite end point (cardiovascular disease) of death, myocardial infarction, or stroke. Subjects were followed up for a median of 210 days (7 months). Mean patient age was 59.1 years, and 21.8% were women. Periprocedural bleeding complications occurred in 1,869 patients (26.7%), and blood transfusion was administered to 189 patients (2.7%). In multivariate analysis, periprocedural bleeding complications were significantly associated with increased risk of the composite outcome for mild (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.64 to 0.97), moderate (HR 2.38, 95% CI 1.78 to 3.20), and severe bleeding complications (HR 3.55, 95% CI 2.20 to 5.73) during follow-up. Also, the necessity of blood transfusion was an important predictor of the composite end point (HR 2.61, 95% CI 1.96 to 3.60). Patients in the United States were more likely to be administered a blood transfusion than non-US patients independently of cardiovascular risk factors. In conclusion, moderate and severe periprocedural bleeding complications increased the risk of mortality and incident cardiovascular events after PCI.
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PMID:Relation of periprocedural bleeding complications and long-term outcome in patients undergoing percutaneous coronary revascularization (from the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events [EXCITE] Trial). 1932 16


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