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https://www.readbyqxmd.com/read/29138609/non-valvular-atrial-fibrillation-impact-of-apixaban-on-patient-outcomes
#1
REVIEW
Adam Ioannou, Irene Tsappa, Sofia Metaxa, Constantinos G Missouris
Atrial fibrillation is the most common arrhythmia worldwide, and carries a significantly increased risk of thromboembolic stroke. Initially, vitamin K antagonists were used as stroke prophylaxis; but more recently, a group of drugs known as novel oral anticoagulants have been developed. Apixaban belongs to this group of drugs, and is a factor Xa inhibitor that has emerged as a popular pharmacological agent worldwide. In this review, we will provide an overview of the pivotal trials in the development of apixaban, while also critically evaluating the new emerging real-world data, and discussing the effectiveness, safety, economic viability and future prospects of apixaban and how it impacts on patient outcomes in those with non-valvular atrial fibrillation...
2017: Patient related Outcome Measures
https://www.readbyqxmd.com/read/29132879/rivaroxaban-with-or-without-aspirin-in-patients-with-stable-coronary-artery-disease-an-international-randomised-double-blind-placebo-controlled-trial
#2
Stuart J Connolly, John W Eikelboom, Jackie Bosch, Gilles Dagenais, Leanne Dyal, Fernando Lanas, Kaj Metsarinne, Martin O'Donnell, Anthony L Dans, Jong-Won Ha, Alexandr N Parkhomenko, Alvaro A Avezum, Eva Lonn, Liu Lisheng, Christian Torp-Pedersen, Petr Widimsky, Aldo P Maggioni, Camilo Felix, Katalin Keltai, Masatsugu Hori, Khalid Yusoff, Tomasz J Guzik, Deepak L Bhatt, Kelley R H Branch, Nancy Cook Bruns, Scott D Berkowitz, Sonia S Anand, John D Varigos, Keith A A Fox, Salim Yusuf
BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries...
November 10, 2017: Lancet
https://www.readbyqxmd.com/read/29131074/tranexamic-acid-failed-to-reverse-the-anticoagulant-effect-and-bleeding-by-an-oral-direct-factor-xa-inhibitor-edoxaban
#3
Yuko Honda, Taketoshi Furugohri, Yoshiyuki Morishima
BACKGROUND/AIMS: Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. METHODS: A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously...
November 3, 2017: Pharmacology
https://www.readbyqxmd.com/read/29126301/coagulation-testing-in-the-core-laboratory
#4
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29120909/rivaroxaban-induced-hepatotoxicity-review-of-the-literature-and-report-of-new-cases
#5
Anna Licata, Fania Puccia, Vania Lombardo, Antonietta Serruto, Maria G Minissale, Ilaria Morreale, Lydia Giannitrapani, Maurizio Soresi, Giuseppe Montalto, Piero L Almasio
AIM/OBJECTIVE/BACKGROUND: Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2008-2016 was carried out...
November 8, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29119147/betrixaban-a-direct-oral-inhibitor-of-activated-factor-x-for-the-prophylaxis-of-venous-thromboembolism-in-patients-hospitalized-for-acute-medical-illness
#6
G Escolar, M Díaz-Ricart, E Arellano-Rodrigo
Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a serious clinical and public health concern. Hospitalization is a major risk factor for developing VTE. Hospital-associated events account for more than 50% of all cases of VTE. Heparins have demonstrated to be efficacious in the prevention of VTE in medically ill patients. Despite the demonstrated efficacy and safety of the available direct oral anticoagulants in the prevention and treatment of different thromboembolic conditions, their net benefit in the prevention of VTE in hospitalized medically ill patients has not been fully confirmed...
August 2017: Drugs of Today
https://www.readbyqxmd.com/read/29117741/%C3%AE-thromboglobulin-may-not-reflect-platelet-activation-during-haemodialysis-with-the-hepran-membrane
#7
Solbjørg Sagedal, Leiv Sandvik, Olav Klingenberg, Per Morten Sandset
BACKGROUND: When blood passes through the extracorporeal circuit during haemodialysis (HD) undesirable effects including platelet degranulation and coagulation activation take place. β-thromboglobulin (β-TG) is a sensitive marker of platelet activation. The aim of this study was to investigate platelet degranulation and coagulation activation during HD with the heparin-coated dialysis membrane HeprAN. METHODS: Four HD sessions were evaluated in each of 12 chronic HD patients...
November 9, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29117605/-new-oral-anticoagulants-noac-in-stroke-treatment
#8
Clemens Küpper, Lars Kellert, Steffen Tiedt, Frank Arne Wollenweber
Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only...
November 8, 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/29111325/inhibition-of-tissue-factor-signaling-in-breast-tumour-xenografts-induces-widespread-changes-in-the-microrna-expression-profile
#9
Esterina D'Asti, G Mark Anderson, Janusz Rak
Tissue factor (TF) is a transmembrane receptor for coagulation factor VII/VIIa that is frequently overexpressed by cancer cells. The TF/VIIa complex acts as the main initiator of the clotting cascade in blood and a trigger of intracellular signaling that changes gene expression and the cellular phenotype. However, pathways mediating these changes are still poorly characterized and especially the impact of TF signals on regulatory microRNA (miR) networks in cancer remains unknown. We show that the monoclonal antibody that selectively neutralises the signaling (but not coagulant) function of human TF (CNTO 2559) inhibits progression of MDA-MB-231 breast cancer xenografts in mice and prolongs animal survival...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29106076/rivaroxaban-reversal-with-prothrombin-complex-concentrate-or-tranexamic-acid-in-healthy-volunteers
#10
J H Levy, K T Moore, M D Neal, D Schneider, V S Marcsisin, J Ariyawansa, J I Weitz
BACKGROUND: Oral factor Xa inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although 4-factor-prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F-PCC partially reverses the prolonged prothrombin time (PT), and fully restores endogenous thrombin potential (ETP). The effect of TXA has not been evaluated...
November 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29105666/-low-or-reduced-semantics-of-the-doses-of-new-oral-anticoagulants
#11
Andrea Rubboli
The four new oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban and edoxaban are marketed in two doses each for the prevention of stroke and/or systemic thromboembolism in non-valvular atrial fibrillation (NVAF). The meaning and indications for use of the lower dose compared with the higher dose are, however, different between the thrombin-inhibitor dabigatran on the one hand and the activated factor X (Xa) inhibitors on the other. These differences stem from the different design of the registration studies where NOACs were compared with warfarin for the prevention of stroke and/or systemic thromboembolism in patients with NVAF...
September 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/29105079/direct-oral-anticoagulants-versus-warfarin-for-preventing-stroke-and-systemic-embolic-events-among-atrial-fibrillation-patients-with-chronic-kidney-disease
#12
REVIEW
Miho Kimachi, Toshi A Furukawa, Kimihiko Kimachi, Yoshihito Goto, Shingo Fukuma, Shunichi Fukuhara
BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin...
November 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29102371/are-factor-xa-inhibitors-effective-thromboprophylaxis-following-hip-fracture-surgery-a-large-national-database-study
#13
Sean T Campbell, Abiram Bala, Sam Y Jiang, Michael J Gardner, Julius A Bishop
INTRODUCTION: The purpose of this study was to evaluate the effectiveness of Factor Xa inhibitors (XaI) for thromboprophylaxis following hip fracture surgery in a large cohort of patients, and compare XaI against warfarin and enoxaparin. METHODS: Patients undergoing hip fracture surgery from 2007 to 2015 were identified in a large claims database. Patients prescribed warfarin, XaI, or enoxaparin within 2 weeks of surgery were identified and grouped into cohorts...
October 31, 2017: Injury
https://www.readbyqxmd.com/read/29100817/edoxaban-improves-acute-venous-thromboembolism-while-preserving-protein-c-and-protein-s-levels
#14
Hiromu Yamazaki, Shusuke Yagi, Yuta Torii, Rie Amano, Yasuyuki Oomichi, Teruaki Sangawa, Daiju Fukuda, Muneyuki Kadota, Takayuki Ise, Rie Ueno, Tomoya Hara, Kenya Kusunose, Tomomi Matsuura, Takeshi Tobiume, Koji Yamaguchi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masashi Akaike, Masataka Sata
BACKGROUND: It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. METHODS AND RESULTS: We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n=37) or warfarin (n=20) in a clinical setting...
October 31, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29097174/medical-management-of-acute-superficial-vein-thrombosis-of-the-saphenous-vein
#15
REVIEW
Sherry D Scovell, Emel A Ergul, Mark F Conrad
OBJECTIVE: Acute superficial vein thrombosis (SVT) of the axial veins, such as the great saphenous vein (GSV), is a common clinical condition that carries with it significant risk of propagation of thrombus, recurrence, and, most concerning, subsequent venous thromboembolism (VTE). Conservative therapy with nonsteroidal anti-inflammatory medication and heat does not prevent extension of thrombus or protect against recurrent or future VTE in patients with extensive SVT (thrombotic segment of at least 5 cm in length)...
October 30, 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/29082360/minor-plasma-lipids-modulate-clotting-factor-activities-and-may-affect-thrombosis-risk
#16
Hiroshi Deguchi, Darlene J Elias, John H Griffin
Different minor abundance plasma lipids significantly influence thrombin generation in vitro and significant differences in such lipids are linked to risk for venous thrombosis. Some plasma sphingolipids including glucosylceramide, lyso-sulfatide and sphingosine have anticoagulant properties whereas, conversely, some plasma phospholipid derivatives, including certain lyso-phospholipids and ethanolamides, have procoagulant properties. Plasma metabolite profiling of venous thrombosis patients showed association of venous thrombosis with decreased plasma long-chain acylcarntines, leading to discovery of their anticoagulant activity as inhibitors of factor Xa...
July 2017: Res Pract Thromb Haemost
https://www.readbyqxmd.com/read/29076814/effects-of-rivaroxaban-on-intimal-hyperplasia-and-smooth-muscle-cell-proliferation-at-the-carotid-artery-anastomosis-site-in-rabbits
#17
Gökmen Akkaya, Çağatay Bilen, Tuğra Gençpınar, Pınar Akokay, Baran Uğurlu
OBJECTIVE: This study aimed to assess the effect of new generation oral, direct factor Xa inhibitor rivaroxaban on intimal hyperplasia and smooth muscle cell proliferation at the carotid artery anastomosis site of rabbits. METHODS: In total, 14 New Zealand male rabbits weighing 3-3.5 kg were randomized into two groups. Group A (7 rabbits) served as the control group and received no medication. Rivaroxaban was perorally administered to group B (7 rabbits) mg/kg/day for 28 days...
October 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29076739/can-system-truncation-speed-up-ligand-binding-calculations-with-periodic-free-energy-simulations
#18
Francesco Manzoni, Jon Uranga, Samuel Genheden, Ulf Ryde
We have investigated whether alchemical free-energy perturbation calculations of relative binding energies can be sped up by simulating a truncated protein. Previous studies with spherical non-periodic systems showed that the number of simulated atoms could be reduced by a factor of 26 without affecting the calculated binding free energies by more than 0.5 kJ/mol on average (Genheden, S. & Ryde, U., J. Chem. Theory Comput., 2012, 8, 1449), leading to 63-fold decrease in the time consumption. However, such simulations are rather slow, owing to the need of a large cut-off radius for the non-bonded interactions...
October 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29072911/the-design-of-small-molecule-active-site-inhibitors-of-the-s1a-family-proteases-as-procoagulant-and-anticoagulant-drugs
#19
Peter M Fischer
Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant management in venous thrombosis. While efficacious, they are difficult to use due to interpatient dose-response variability and the risks of bleeding. The approval of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation for the development of direct oral anticoagulants (DOAC), and currently such inhibitors of thrombin and fXa are in clinical use. These agents can be used without regular coagulation monitoring but the inherent risk of bleeding complications associated with blocking the common coagulation pathway remains...
October 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29071333/association-of-anti-factor-xa-guided-dosing-of-enoxaparin-with-venous-thromboembolism-after-trauma
#20
Charles A Karcutskie, Arjuna Dharmaraja, Jaimin Patel, Sarah A Eidelson, Anish B Padiadpu, Arch G Martin, Gabriel Lama, Edward B Lineen, Nicholas Namias, Carl I Schulman, Kenneth G Proctor
Importance: The efficacy of anti-factor Xa (anti-Xa)-guided dosing of thromboprophylaxis after trauma remains controversial. Objective: To assess whether dosing of enoxaparin sodium based on peak anti-Xa levels is associated with the venous thromboembolism (VTE) rate after trauma. Design, Setting, and Participants: Retrospective review of 950 consecutive adults admitted to a single level I trauma intensive care unit for more than 48 hours from December 1, 2014, through March 31, 2017...
October 25, 2017: JAMA Surgery
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