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Vorapaxar

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https://www.readbyqxmd.com/read/28277861/state-transition-model-vorapaxar-added-to-standard-antiplatelet-therapy-to-prevent-thrombosis-post-myocardial-infarction-or-peripheral-artery-disease
#1
Mark Du, Monica Chase, Mustafa Oguz, Glenn Davies
OBJECTIVE: To evaluate long-term health benefits and risks of adding vorapaxar (VOR) to the standard care antiplatelet therapy (SC) of aspirin and/or clopidogrel, among a population with a recent myocardial infarction (MI) and/or peripheral artery disease (PAD). RESEARCH DESIGN AND METHODS: In a state-transition model, patients transition between health states (event-free, recurrent MI, stroke, death), while at risk of experiencing non-transition-related revascularization and non-fatal bleeding events...
March 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28267691/vorapaxar-and-amyotrophic-lateral-sclerosis-coincidence-or-adverse-association
#2
REVIEW
Victor L Serebruany, Seth D Fortmann, Daniel F Hanley, Moo Hyun Kim
BACKGROUND: Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, is currently approved for post myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The vorapaxar safety profile was acceptable. However, aside from heightened bleeding risks, excesses of solid cancers and diplopia, there were more amyotrophic lateral sclerosis (ALS) diagnoses after vorapaxar. STUDY QUESTION: To assess the Food and Drug Administration (FDA) reviews on the potential association of vorapaxar with ALS...
March 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28267389/molecular-requirements-involving-the-human-platelet-protease-activated-receptor-4-mechanism-of-activation-by-peptide-analogues-of-its-tethered-ligand
#3
I C Moschonas, T F Kellici, T Mavromoustakos, P Stathopoulos, V Tsikaris, V Magafa, A G Tzakos, A D Tselepis
Thrombin is the most potent agonist of human platelets and its effects are primarily mediated through the protease-activated receptors (PARs)-1 and -4. Although PAR-1 has higher affinity for thrombin than PAR-4, both receptors contribute to thrombin-mediated actions on platelets. Recently, a potent and selective PAR-1 antagonist (vorapaxar) was approved for clinical use in selected patients. In contrast, despite the fact that several PAR-4 antagonists have been developed, few of them have been tested in clinical trials...
March 7, 2017: Platelets
https://www.readbyqxmd.com/read/28230176/antithrombotic-therapy-for-patients-with-stemi-undergoing-primary-pci
#4
REVIEW
Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo
Antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Intravenous anticoagulant drugs available for PPCI include the indirect thrombin inhibitors unfractionated heparin and low-molecular-weight heparin, and the direct thrombin inhibitor bivalirudin. Intravenous antiplatelet drugs mainly include glycoprotein IIb/IIIa inhibitors and the P2Y12-receptor inhibitor cangrelor...
February 23, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28148395/tissue-factor-factor-viia-complex-triggers-protease-activated-receptor-2-dependent-growth-factor-release-and-migration-in-ovarian-cancer
#5
Alice Chanakira, Pamela R Westmark, Irene M Ong, John P Sheehan
OBJECTIVE: Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. METHODS: TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines...
April 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28135897/pharmacokinetic-drug-evaluation-of-vorapaxar-for-secondary-prevention-after-acute-coronary-syndrome
#6
REVIEW
Jose-Angel Perez-Rivera, Jairo Monedero-Campo, Clara Cieza-Borrella, Pablo Ruiz-Perez
Vorapaxar is the first protease-activated receptor-1 inhibitor approved for clinical use. Its main indication is the reduction in thrombotic cardiovascular events in patients with previous myocardial infarction or symptomatic peripheral artery disease. Areas covered: This article reviews the pharmacokinetics of vorapaxar and its potential use in secondary prevention after an acute coronary syndrome. Expert opinion: Vorapaxar inhibits platelet aggregation mediated by thrombin. This effect is carried out without affecting to coagulation parameters and bleeding times...
March 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28063023/vorapaxar-the-current-role-and-future-directions-of-a-novel-protease-activated-receptor-antagonist-for-risk-reduction-in-atherosclerotic-disease
#7
REVIEW
Rebecca J Gryka, Leo F Buckley, Sarah M Anderson
INTRODUCTION: Despite the current standard of care, patients with cardiovascular disease remain at a high risk for recurrent events. Inhibition of thrombin-mediated platelet activation through protease-activated receptor-1 antagonism may provide reductions in atherosclerotic disease beyond those achievable with the current standard of care. OBJECTIVE: Our primary objective is to evaluate the clinical literature regarding the role of vorapaxar (Zontivity™) in the reduction of cardiovascular events in patients with a history of myocardial infarction and peripheral artery disease...
March 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28062625/high-sensitivity-troponin-i-in-stable-patients-with-atherosclerotic-disease-in-the-tra-2%C3%A2-p-timi-50-trial
#8
Alon Eisen, Marc P Bonaca, Petr Jarolim, Benjamin M Scirica, Harvey D White, Michal Tendera, Mikael Dellborg, Jose C Nicolau, Joao Morais, Keith A A Fox, Erin A Bohula, Sabina A Murphy, Eugene Braunwald, David A Morrow
BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined. METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days)...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/27810296/safety-and-efficacy-of-vorapaxar-in-secondary-prevention-of-atherosclerotic-disease-a-meta-analysis-of-randomized-control-trials
#9
Abhishek Sharma, Gérard Helft, Aakash Garg, Sahil Agrawal, Saurav Chatterjee, Carl J Lavie, Sunny Goel, Debabrata Mukherjee, Jonathan D Marmur
OBJECTIVE: To study the cumulative evidence for vorapaxar use in patients with atherosclerotic cardiovascular disease. METHODS: A systematic review of randomized control trials in MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases comparing vorapaxar with placebo was performed. Pre-specified efficacy endpoints were all-cause mortality, CV mortality, myocardial infarction (MI), ischemic stroke and repeat revascularization. The pre-specified safety endpoint was intracranial hemorrhage (ICH) and a composite of TIMI major and minor bleeding...
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27765313/appropriate-use-of-vorapaxar-in-patients-with-peripheral-artery-disease
#10
Robert D Safian
No abstract text is available yet for this article.
October 24, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/27765312/peripheral-revascularization-in-patients-with%C3%A2-peripheral-artery-disease-with%C3%A2-vorapaxar-insights-from-the-tra-2%C3%A2-p-timi-50-trial
#11
Marc P Bonaca, Mark A Creager, Jeffrey Olin, Benjamin M Scirica, Ian C Gilchrist, Sabina A Murphy, Erica L Goodrich, Eugene Braunwald, David A Morrow
OBJECTIVES: The aim of this study was to determine whether the reduction in peripheral revascularization with vorapaxar in patients with peripheral artery disease (PAD) is directionally consistent across indications, including acute limb ischemia, progressively disabling symptoms, or both. BACKGROUND: The protease-activated receptor-1 antagonist vorapaxar reduces peripheral revascularization in patients with PAD. METHODS: The TRA 2°P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50) trial randomized 26,449 patients with histories of myocardial infarction, stroke, or symptomatic PAD to vorapaxar or placebo on a background of standard therapy...
October 24, 2016: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/27541932/biotransformation-of-fluorophenyl-pyridine-carboxylic-acids-by-the-model-fungus-cunninghamella-elegans
#12
William Palmer-Brown, Brian Dunne, Yannick Ortin, Mark A Fox, Graham Sandford, Cormac D Murphy
1. Fluorine plays a key role in the design of new drugs and recent FDA approvals included two fluorinated drugs, tedizolid phosphate and vorapaxar, both of which contain the fluorophenyl pyridyl moiety. 2. To investigate the likely phase-I (oxidative) metabolic fate of this group, various fluorinated phenyl pyridine carboxylic acids were incubated with the fungus Cunninghamella elegans, which is an established model of mammalian drug metabolism. 3. (19)F NMR spectroscopy established the degree of biotransformation, which varied depending on the position of fluorine substitution, and gas chromatography-mass spectrometry (GC-MS) identified alcohols and hydroxylated carboxylic acids as metabolites...
September 15, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27502866/effect-of-age-on-efficacy-and-safety-of-vorapaxar-in-patients-with-non-st-segment-elevation-acute-coronary-syndrome-insights-from-the-thrombin-receptor-antagonist-for-clinical-event-reduction-in-acute-coronary-syndrome-tracer-trial
#13
Luciana V Armaganijan, Karen P Alexander, Zhen Huang, Pierluigi Tricoci, Claes Held, Frans Van de Werf, Paul W Armstrong, Philip E Aylward, Harvey D White, David J Moliterno, Lars Wallentin, Edmond Chen, Robert A Harrington, John Strony, Kenneth W Mahaffey, Renato D Lopes
BACKGROUND: Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. METHODS: Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial...
August 2016: American Heart Journal
https://www.readbyqxmd.com/read/27489245/increased-benefit-with-vorapaxar-use-in-patients-with-a-history-of-myocardial-infarction-and-diabetes-mellitus-what-the-data-show-us
#14
Iraklis C Moschonas, Alexandros D Tselepis
Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial metabolic disease mainly characterized by hyperglycemia and insulin resistance. Abnormal platelet reactivity associated with an increased risk of cardiovascular disease (CVD) is also a feature characteristic of patients with T2DM. Dual antiplatelet therapy consisting of aspirin and an adenosine diphosphate platelet P2Y12 receptor antagonist, such as clopidogrel, represents the standard antithrombotic regimen for the secondary prevention of CVD risk in T2DM...
August 3, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27440003/atherothrombotic-risk-stratification-and-the-efficacy-and-safety-of-vorapaxar-in-patients-with-stable-ischemic-heart-disease-and-previous-myocardial-infarction
#15
RANDOMIZED CONTROLLED TRIAL
Erin A Bohula, Marc P Bonaca, Eugene Braunwald, Philip E Aylward, Ramon Corbalan, Gaetano M De Ferrari, Ping He, Basil S Lewis, Piera A Merlini, Sabina A Murphy, Marc S Sabatine, Benjamin M Scirica, David A Morrow
BACKGROUND: Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. METHODS: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2...
July 26, 2016: Circulation
https://www.readbyqxmd.com/read/27431644/universal-classification-system-type-of-incident-myocardial-infarction-in-patients-with-stable-atherosclerosis-observations-from-thrombin-receptor-antagonist-in-secondary-prevention-of-atherothrombotic-ischemic-events-tra-2%C3%A2-p-timi-50
#16
Stephen K Kidd, Marc P Bonaca, Eugene Braunwald, Gaetano M De Ferrari, Basil S Lewis, Piera A Merlini, Sabina A Murphy, Benjamin M Scirica, Harvey D White, David A Morrow
BACKGROUND: Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first-in-class platelet protease-activated receptor -1 antagonist, on new or recurrent MI. METHODS AND RESULTS: We analyzed data from TRA 2°P-TIMI 50, a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar...
July 18, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27398626/vorapaxar-emerging-evidence-and-clinical-questions-in-a-new-era-of-par-1-inhibition
#17
REVIEW
Leo Ungar, Fatima Rodriguez, Kenneth W Mahaffey
Despite the use of therapies recommended in practice guidelines for secondary prevention in patients with atherosclerotic coronary artery disease, the residual risk for cardiovascular events remains high. Some of the residual risk is believed to result from incomplete platelet inhibition with current therapy. Vorapaxar is a first-in-class, novel antiplatelet agent that acts by antagonizing the PAR-1 receptor, inhibiting thrombin-mediated platelet activation. Vorapaxar was recently approved by the Food and Drug Administration for secondary prevention of cardiovascular events in patients with a history of myocardial infarction or peripheral artery disease who do not have a history of transient ischemic attack or stroke...
November 2016: Coronary Artery Disease
https://www.readbyqxmd.com/read/27366081/impact-of-selective-platelet-inhibition-in-reducing-cardiovascular-risk-role-of-vorapaxar
#18
REVIEW
Judy Wm Cheng
This article reviews the pharmacology, clinical efficacy, and safety of vorapaxar in reducing cardiovascular risk. Vorapaxar is a tricyclic himbacine-derived reversible inhibitor of platelet surface protease activator receptor-1, which prevents thrombin from activating platelets. Two Phase III clinical trials and multiple subanalyses from the two trials with vorapaxar have been published. In patients with recent acute coronary syndrome, vorapaxar, when added to standard therapy, did not reduce the composite cardiovascular end point...
2016: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/27354285/elevated-angiopoietin-2-level-in-patients-with-continuous-flow-left-ventricular-assist-devices-leads-to-altered-angiogenesis-and-is-associated-with-higher-nonsurgical-bleeding
#19
Corey E Tabit, Phetcharat Chen, Gene H Kim, Savitri E Fedson, Gabriel Sayer, Mitchell J Coplan, Valluvan Jeevanandam, Nir Uriel, James K Liao
BACKGROUND: Nonsurgical bleeding is the most common adverse event in patients with continuous-flow left ventricular assist devices (LVADs) and is caused by arteriovenous malformations. We hypothesized that deregulation of an angiogenic factor, angiopoietin-2 (Ang-2), in patients with LVADs leads to increased angiogenesis and higher nonsurgical bleeding. METHODS: Ang-2 and thrombin levels were measured by ELISA and Western blotting, respectively, in blood samples from 101 patients with heart failure, LVAD, or orthotopic heart transplantation...
July 12, 2016: Circulation
https://www.readbyqxmd.com/read/27319946/novel-anti-platelets-in-stable-coronary-artery-disease
#20
Nikolaos Papageorgiou, Effimia Zacharia, Adam Ioannou, Onkar Rehal, Konstantinos Zacharias, Gerasimos Siasos, Dimitris Tousoulis
BACKGROUND: Apart from the acute thrombotic complications that lead to acute coronary syndromes (ACS), platelet activation also plays an important role in the initiation and progression of atherosclerosis. In addition, it is speculated that anti-platelet therapy can be beneficial for patients with stable coronary artery disease (CAD). Of note, patients on optimal anti-platelet treatment still experience thrombotic events, whereas complications, such as bleeding, cannot be ignored. In this light, novel antiplatelet regimens have been used to minimize the residual platelet activation without compromising normal haemostasis...
2016: Current Pharmaceutical Design
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