Read by QxMD icon Read


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...
January 29, 2017: Gynecologic Oncology
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...
January 30, 2017: Expert Opinion on Drug Metabolism & Toxicology
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...
January 6, 2017: Drugs in R&D
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
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
Robert D Safian
No abstract text is available yet for this article.
October 24, 2016: JACC. Cardiovascular Interventions
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
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
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
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
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
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
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
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
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
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
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
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...
2016: Current Pharmaceutical Design
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
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)...
December 2016: Current Eye Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"