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Vorapaxar

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https://www.readbyqxmd.com/read/27810296/safety-and-efficacy-of-vorapaxar-in-secondary-prevention-of-atherosclerotic-disease-a-meta-analysis-of-randomized-control-trials
#1
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...
October 29, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27765313/appropriate-use-of-vorapaxar-in-patients-with-peripheral-artery-disease
#2
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
#3
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
#4
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 GC-MS identified alcohols and hydroxylated carboxylic acids as metabolites...
August 19, 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
#5
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
#6
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
#7
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
#8
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 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
#9
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
#10
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
#11
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
#12
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 the normal homeostasis...
June 17, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27304196/effect-of-vorapaxar-alone-and-in-combination-with-aspirin-on-bleeding-time-and-platelet-aggregation-in-healthy-adult-subjects
#13
W K Kraft, J H Gilmartin, D L Chappell, F Gheyas, B M Walker, S Nagalla, U P Naik, J C Horrow, R E Wrishko, S Zhang, M S Anderson
The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed...
August 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27281329/antiplatelet-treatment-in-peripheral-arterial-disease-the-role-of-novel-antiplatelet-agents
#14
Chris Klonaris, Nikolaos Patelis, Anja Drebes, Sean Matheiken, Theodoros Liakakos
BACKGROUND: Acetylsalicylic acid and clopidogrel are two antiplatelet agents currently used in the therapy of peripheral arterial disease. Cilostazol also inhibits platelet aggegration. These agents present limitations that novel antiplatelet agents may overcome. OBJECTIVE: The aim of this manuscript is to review current data on the use of novel antiplatelet agents in peripheral arterial disease. METHOD: An extensive search in the English medical literature has yielded a number of publications on a number of novel antiplatelet agents; atopaxar, vorapaxar, cangrelor, ticagrelor, elinogrel, and prasugrel...
June 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27262432/a-state-transition-model-for-health-outcomes-associated-with-vorapaxar-treatment-as-an-add-on-to-standard-care-antiplatelet-therapy-in-the-prevention-of-thrombotic-events-for-patients-with-a-recent-myocardial-infarction
#15
John D Whalen, Glenn Davies, Mark Du, Mustafa Oguz, Lori D Bash, Ipek Ozer-Stillman
BACKGROUND: The TRA 2°P-TIMI 50 trial showed the addition of vorapaxar to standard care (SC) antiplatelet therapy reduced the combined risk of death, myocardial infarction (MI), and stroke, while exhibiting an increase in moderate, but not other bleeding events. OBJECTIVE: Our objective was to estimate the long-term health benefits and risks of vorapaxar as an add-on to SC treatment (lifetime aspirin and up to 12 months of clopidogrel) for patients with a prior MI and without a history of cerebrovascular disease...
August 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/27261371/upregulation-of-thrombin-matrix-metalloproteinase-1-protease-activated-receptor-1-chain-in-proliferative-diabetic-retinopathy
#16
Ahmed M Abu El-Asrar, Kaiser Alam, Mohd Imtiaz Nawaz, Ghulam Mohammad, Kathleen Van den Eynde, Mohammad Mairaj Siddiquei, Ahmed Mousa, Gert De Hertogh, Ghislain Opdenakker
PURPOSE: Selective proteolytic activation of protease-activated receptor-1 (PAR1) by thrombin and matrix metalloproteinase-1 (MMP-1) plays a central role in enhancing angiogenesis. We investigated the expression levels of thrombin, MMP-1, and PAR1 and correlated these levels with vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of PAR1 and thrombin in the retinas of diabetic rats and PAR1 in human retinal microvascular endothelial cells (HRMEC) following exposure to high-glucose, the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the hypoxia mimetic agent cobalt chloride (CoCl2)...
June 3, 2016: Current Eye Research
https://www.readbyqxmd.com/read/27162212/lack-of-concordance-between-local-investigators-angiographic-core-laboratory-and-clinical-event-committee-in-the-assessment-of-stent-thrombosis-results-from-the-tracer-angiographic-substudy
#17
Christopher J Popma, Shi Sheng, Serge Korjian, Yazan Daaboul, Gerald Chi, Pierluigi Tricoci, Zhen Huang, David J Moliterno, Harvey D White, Frans Van de Werf, Robert A Harrington, Lars Wallentin, Claes Held, Paul W Armstrong, Philip E Aylward, John Strony, Kenneth W Mahaffey, C Michael Gibson
BACKGROUND: Stent thrombosis (ST) is an important end point in cardiovascular clinical trials. Adjudication is traditionally based on clinical event committee (CEC) review of case report forms and source documentation rather than angiograms. However, the degree to which this method of adjudication is concordant with the review of independent angiographic core laboratories (ACLs) has not been studied. This report represents the first assessment of variability between local investigators (LIs), a CEC, and an ACL...
May 2016: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/27151345/validation-of-barc-bleeding-criteria-in-patients-with-acute-coronary-syndromes-the-tracer-trial
#18
Pascal Vranckx, Harvey D White, Zhen Huang, Kenneth W Mahaffey, Paul W Armstrong, Frans Van de Werf, David J Moliterno, Lars Wallentin, Claes Held, Philip E Aylward, Jan H Cornel, Christoph Bode, Kurt Huber, José C Nicolau, Witold Ruzyllo, Robert A Harrington, Pierluigi Tricoci
BACKGROUND: The Bleeding Academic Research Consortium (BARC) scale has been proposed to standardize bleeding endpoint definitions and reporting in cardiovascular trials. Validation in large cohorts of patients is needed. OBJECTIVES: This study sought to investigate the relationship between BARC-classified bleeding and mortality and compared its prognostic value against 2 validated bleeding scales: TIMI (Thrombolysis In Myocardial Infarction) and GUSTO (Global Use of Strategies to Open Occluded Arteries)...
May 10, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27134460/vorapaxar-a-novel-agent-to-be-considered-in-the-secondary-prevention-of-myocardial-infarction
#19
REVIEW
Obamiro Kehinde, Rotimi Kunle
Patients receiving therapy for the secondary prevention of myocardial infarction (MI) are still at high risk of a major cardiovascular event or death despite the use of currently available treatment strategy. Vorapaxar, an oral protease-activated receptor antagonist, is a novel antiplatelet drug that has been recently approved to provide further risk reduction. The results of two Phase III trials (thrombin receptor antagonists for clinical event reduction and the TRA 2°P-TIMI 50) have showed that vorapaxar, in addition to standard of care therapy, has the potential to provide further risk reduction in patients with prior MI...
April 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/27131284/expression-of-pro-inflammatory-genes-in-human-endothelial-cells-comparison-of-rivaroxaban-and-dabigatran
#20
Peter Ellinghaus, Elisabeth Perzborn, Peter Hauenschild, Christoph Gerdes, Stefan Heitmeier, Mayken Visser, Holger Summer, Volker Laux
INTRODUCTION: In addition to its central role in coagulation, thrombin is involved in non-hemostatic activities such as inflammation. Direct inhibition of thrombin activity (e.g. with dabigatran) or reducing its generation by inhibition of Factor Xa (e.g. with rivaroxaban) may therefore have anti-inflammatory effects. MATERIALS AND METHODS: Microarray experiments were performed to identify transcriptome-wide changes in mRNA expression levels induced by thrombin in the presence and absence of the PAR-1 antagonist vorapaxar in primary human umbilical vein endothelial cells (HUVECs)...
June 2016: Thrombosis Research
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