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The antiphosholipid syndrome (APS) is an autoimmune disorder, characterized by the presence of vascular thrombosis and/or pregnancy morbidity in a patient with positive laboratory tests for antiphospholipid antibodies. The patients with APS are in the high risk of rethrombosis. We report the case of 43-year-old female presenting with recurrent acute myocardial infarction with ST-segment elevation because of recurrent coronary thrombosis in coronary left anterior descending artery (LAD) and circumflex coronary artery (Cx) resulting in four percutaneous coronary interventions (PCI), associated with the presence of plasma antiphospholipid antibodies. Patient received seven stents to LAD and the aspiration of thrombus from Cx artery was performed. Pharmacotherapy included full antithrombotic treatment consisted with antiplatelet drugs such as: aspirin, clopidogrel followed by prasugrel, glycoprotein IIb/IIIa receptor antagonists and anticoagulants such as heparin followed by warfarin as well as steroids. At 1-year follow-up, controlled coronary angiography confirmed the good effect of PCI without any signs of stenosis or rethrombosis and highlighted the important role of antithrombotic treatment in patients with APS.
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Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation.
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Subjects (2732: 2062 whites; 670 blacks) hospitalized with acute myocardial infarction enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of whites (79%) and blacks (64.4%) were discharged on clopidogrel. Among whites, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mortality (adjusted hazards ratio [HR]: 1.70; confidence interval [CI]: 1.01-2.86; P=0.046) and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI: 0.95-4.63; P=0.066). Among blacks, increased 1-year mortality was associated with the gain-of-function CYP2C19*17 allele (adjusted HR for *1/*17 versus *1/*1: 2.02; CI: 0.92-4.44; *17/*17 versus *1/*1: 8.97; CI: 3.34-24.10; P<0.0001) and the CYP1A2*1C allele (adjusted HR for *1/*1C versus *1/*1: 1.89; CI: 0.85-4.22; *1C/*1C versus *1/*1: 4.96; CI: 1.69-14.56; P=0.014). Bleeding events were significantly more common among black carriers of CYP2C19*17 or CYP1A2*1C.
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Stent thrombosis (ST) remains a major adverse outcome of percutaneous coronary intervention (PCI). We examined potential associations between high on treatment platelet reactivity and the risk of ST and assessed the effects of increased antiplatelet dosage on platelet inhibition.
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The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation remains controversial. The primary aim of our study was to evaluate the impact of optimal DAPT duration on bleeding events between 6 and 12 months after biodegradable polymer-coated DES implantation. The secondary aim is to determine the predictors and prognostic implications of bleeding.
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This Practice Point commentary discusses Dember et al.'s randomized, double-blind, placebo-controlled trial of clopidogrel treatment after the creation of an arteriovenous fistula for dialysis. In total, 877 patients were treated with either placebo or clopidogrel (300 mg loading dose followed by 75 mg daily) for 6 weeks after fistula creation. Treatment with clopidogrel was associated with a significantly lower rate of fistula thrombosis than was placebo (12.2% vs 19.5%; P = 0.018). This reduction did not, however, lead to any changes in the secondary end point of attaining a useable access for dialysis; therefore, routine treatment with clopidogrel after fistula creation was not of clinical benefit in this well-conducted trial.
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All patients (n = 172) received aspirin (loading dose 300 mg and maintenance dose 100 mg/d) and clopidogrel (loading dose 600 mg and maintenance dose 75 mg/d) during the therapy. They were randomized to receive omeprazole (20 mg/d) or placebo for 30 days. Residual platelet activities in the adenosine 5'-diphosphate (ADP) pathway were detected on the fifth day after PCI with thrombelastography (TEG)-mapping. The clinical events were recorded after one month.
Unsedated t-EGD was attempted in 89 patients, performed in 52 (5 failures, 28 contraindications) and the procedure was converted under sedation for 2 patients. Based on ASA classification, clinical (blood pressure, hemodynamical failure) and biological variables (hemoglobin, platelets, creatinine), these patients were less severe than in the other groups. Pre-endoscopic Rockall and Blatchford scores were significantly lower in this group. More patients in this group presented significant cardiovascular co-morbidity (47.2%), taking aspirin, clopidogrel and/or anticoagulant.
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In patients with ACS, ticagrelor pharmacokinetics is influenced by three genetic loci (SLCO1B1, UGT2B7, and CYP3A4). However, the modest genetic effects on ticagrelor plasma levels did not translate into any detectable effect on efficacy or safety during ticagrelor treatment.
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The choice of antiplatelet therapy among Asian populations for the treatment of acute coronary syndrome (ACS) is complicated owing to the high prevalence of cytochrome P450 2C19 (CYP2C19) genetic polymorphism that has been associated with reduced efficacy of clopidogrel. Ticagrelor is a potent but more expensive alternative antiplatelet agent that is not affected by CYP2C19 polymorphism. This study aimed to evaluate the cost-effectiveness, from the Hong Kong health-care provider's perspective, of CYP2C19*2 genotype-guided selection of antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among ACS patients who undergo percutaneous coronary intervention (PCI). In the present study, a two-part model consisting of a 1-year decision tree and a lifetime Markov model was built to simulate the progress of a typical cohort of 60-year-old Chinese patients until age 85 years and compare three treatment strategies: (i) generic clopidogrel or ticagrelor based on CYP2C19*2 genotype, (ii) universal use of generic clopidogrel or (iii) universal use of ticagrelor for all patients. Incremental cost-effectiveness ratios (ICERs) of <1 gross domestic product per capita locally (US dollar (USD)42 423/quality-adjusted life year (QALY)) were considered cost-effective. Base-case results showed universal ticagrelor use was cost-effective compared with universal clopidogrel, but was dominated by genotype-guided treatment. Genotype-guided treatment was cost-effective compared with universal clopidogrel use (ICER of USD2560/QALY). Sensitivity analysis demonstrated that with the cost of genotype testing up to USD400, CYP2C19*2 genotype-guided antiplatelet treatment remained a cost-effective strategy compared with either universal use of generic clopidogrel or ticagrelor in post-PCI ACS patients in Hong Kong.The Pharmacogenomics Journal advance online publication, 24 January 2017; doi:10.1038/tpj.2016.94.