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Antithrombotic therapy for prevention of thrombosis

Lai Heng Lee
The group of new oral anticoagulants or NOACs, now termed direct oral anticoagulants or DOACs, with their favourable results from large scale phase III clinical trials, represent a major advancement and expanded armamentarium in antithrombotic therapy. Dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Usage of the DOACs is expected to increase as clinicians gain more experience and reassurance with data from the real world studies which are generally consistent with that from clinical trials...
2016: Thrombosis Journal
Qing-Song Yin, Lin Chen, Rui-Hua Mi, Hao Ai, Jun-Jie Yin, Xiao-Juan Liu, Xu-Dong Wei
BACKGROUND Currently available antithrombotic prophylaxis is not perfectly reliable in elderly patients. The aim of this retrospective study was to evaluate the efficacy and safety of Compound Danshen Tablet (CDT) in preventing thromboembolism in multiple myeloma (MM) patients treated with thalidomide-based regimens. MATERIAL AND METHODS MM patients treated with thalidomide-based regimens were retrospectively reviewed between January 2008 and March 2015. Patients were categorized into 3 cohorts based on thromboembolic prophylaxis used: CDT, Warfarin Tablet, and no prophylaxis...
October 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Willem M Lijfering, Joseph S Biedermann, Marieke J H A Kruip, Frank W G Leebeek, Frits R Rosendaal, Suzanne C Cannegieter
Statins may be causally associated with a decreased risk of venous thrombosis. If so, this could be a substantive breakthrough since statins do not increase the risk of bleeding and could therefore be used as a safer antithrombotic drug. However, scepticism exists on the observed reduction of venous thrombosis by statins, as it may have been confounded by healthy user effects or other biases. Areas covered: The main focus of this review will be the biases that may have arisen in clinical studies that investigated the relationship between statin use and risk of venous thrombosis...
October 19, 2016: Expert Review of Hematology
Riccardo Cappato, Robert Welsh
The vast clinical research programme for the direct, oral factor Xa inhibitor rivaroxaban has generated a wealth of data since the first rivaroxaban approval in 2008 for the prevention of venous thromboembolism (VTE) in patients undergoing elective hip or knee replacement surgery. While rivaroxaban is widely used across a spectrum of seven indications, there is continuous commitment to investigating its wider benefits in new indications and attempts to refine current evidence. Key data from recently completed randomised controlled trials (RCTs) have shown that rivaroxaban is a feasible anticoagulation option for patients with non-valvular atrial fibrillation (NVAF) undergoing cardioversion or catheter ablation...
September 28, 2016: Thrombosis and Haemostasis
Christopher P Cannon, Savion Gropper, Deepak L Bhatt, Stephen G Ellis, Takeshi Kimura, Gregory Y H Lip, Ph Gabriel Steg, Jurriën M Ten Berg, Jenny Manassie, Jörg Kreuzer, Jon Blatchford, Joseph M Massaro, Martina Brueckmann, Ernesto Ferreiros Ripoll, Jonas Oldgren, Stefan H Hohnloser
Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking...
August 26, 2016: Clinical Cardiology
Haoming Zhang, D Adam Lauver, Hui Wang, Duxin Sun, Paul F Hollenberg, Y Eugene Chen, Yoichi Osawa, Daniel T Eitzman
Clopidogrel is a prodrug that requires bioactivation by cytochrome P450 (P450) enzymes to a pharmacologically active metabolite for antiplatelet action. The clinical limitations of clopidogrel are in large part due to its poor pharmacokinetics resulting from inefficient bioactivation by P450s. In this study, we determined the pharmacokinetics and pharmacodynamics of a novel conjugate of clopidogrel, referred to as ClopNPT, in animal models and we evaluated its potential to overcome the limitations of clopidogrel...
October 2016: Journal of Pharmacology and Experimental Therapeutics
Tingting Han, Guangping Zhang, Dong Yan, Hong Yang, Tonghui Ma, Zuguang Ye
Plasminogen activator inhibitor-1 (PAI-1) is a key negative regulator of the fibrinolytic system. Elevated levels of PAI-1 are associated with thrombosis and cardiovascular and metabolic diseases. Inhibition of PAI-1 activity represents a new strategy for antithrombotic and antifibrinolysis therapies. In this study, we systematically investigated the inhibitory effect of shikonin on PAI-1 activity. In the chromogenic substrate-based urokinase (uPA)/PAI-1 assay, we found that shikonin inhibited human PAI-1 activity with IC50 values of 30...
September 2016: Fitoterapia
Mauro Li Calzi, Angelo Placci, Daniela Lina, Francesca Grassi, Giorgia Paoli, Michele Bianconcini, Maria Alberta Cattabiani, Alberto Menozzi
We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed...
June 2016: Giornale Italiano di Cardiologia
Robert F Storey, Akanksha Sinha
INTRODUCTION: Despite advances in antiplatelet therapy, the optimum antithrombotic regimen during percutaneous coronary intervention (PCI) remains to be determined. Cangrelor is an intravenous, reversibly-binding platelet P2Y12 receptor antagonist with ultra-rapid onset and offset of action that is approved in Europe and United States for use in patients undergoing PCI. This article describes the background for the development of cangrelor, the biology, pharmacology and clinical evidence supporting its use, and its likely position in the future...
September 2016: Expert Review of Cardiovascular Therapy
Zbigniew Krasiński, Beata Krasińska, Łukasz Dzieciuchowicz, Tomasz Urbanek, Marcin Gabriel
A close causal relationship between cancer and venous thrombosis gives rise to questions about the effect of treatment modalities, in particular of the administered drugs, in patients with cancer-related venous thrombosis. An increased risk of chemotherapy-associated venous thromboembolism (VTE) has been well documented, while the effect of heparins used in VTE treatment on the disease course and prognosis in cancer patients has not been fully elucidated. This paper discusses the outcomes of the studies conducted so far investigating the role of heparins, in particular, low-molecular-weight heparins (LMWHs), in the prevention of thrombosis in cancer patients...
June 23, 2016: Polskie Archiwum Medycyny Wewnętrznej
John M Kittelson, Philippe Gabriel Steg, Jonathan L Halperin, Neil A Goldenberg, Sam Schulman, Alex C Spyropoulos, Craig M Kessler, Alexander G G Turpie, Neal R Cutler, William R Hiatt
Clinical trials of antithrombotic therapy require a cohesive assessment of benefit and risk. A new graphical method to represent the bivariate relation of benefit and risk in trials of antithrombotic drugs is described and illustrated using published data from the four major registration clinical trials of non-vitamin K oral anticoagulants (NOACs) totalling 71,683 patients for prevention of thromboembolic events (TE) in patients with atrial fibrillation (RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI48). A curve representing a null hypothesis defines a region of benefit on a two-dimensional plane...
August 30, 2016: Thrombosis and Haemostasis
Theodoros A Zografos, Demosthenes G Katritsis
BACKGROUND: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy has been shown to effectively prevent stent thrombosis and other ischemic cardiovascular event. The frequent occurrence of atrial fibrillation (AF) and concomitant CAD in the same individuals, suggests that clinicians will encounter many patients treated with PCI who will require anticoagulant treatment for the prevention of the thromboembolic complications of AF...
June 22, 2016: Current Pharmaceutical Design
T Thériault, M Touchette, V Goupil, D Echenberg, L Lanthier
RATIONALE: Venous thromboembolic disease is a source of significant morbidity in hospitalized patients. The American College of Chest Physicians published the ninth edition of antithrombotic therapy and prevention guidelines (AT9) in 2012, addressing thromboprophylaxis in hospitalized patients. A notable difference from previous guidelines was utilization of risk assessment models for thrombosis and bleeding to classify patients into risk categories. AIM: This study's objective was to evaluate thromboprophylaxis adherence to AT9 guidelines in a population of patients at the Centre intégré universitaire de santé et de service sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke...
June 5, 2016: Journal of Evaluation in Clinical Practice
R De Vecchis, C Baldi, S Cantatrione
This article covers the main unsolved issues regarding the potential role that the patent foramen ovale (PFO) plays in the genesis of so-called cryptogenic stroke. Some brief notions of the anatomy and epidemiology of the PFO are outlined. Subsequently, the results of the three trials on secondary prevention (medical therapy vs. transcatheter closure) in patients with PFO and a history of cryptogenic stroke are presented. The conflicting results of numerous meta-analyses derived from the three randomized controlled trials are discussed...
June 2, 2016: Herz
Hazem Elewa, Dina Ahmed, Geoffrey D Barnes
Patients with atrial fibrillation (AF) who are treated with oral anticoagulants often have concurrent coronary artery disease. Triple oral antithrombotic therapy (TOAT) is often necessity to prevent stent thrombosis or myocardial infarction associated with percutaneous coronary intervention or acute coronary syndrome in patients with comorbid coronary artery disease and AF. Although the use of TOAT (aspirin, clopidogrel, and warfarin) has excellent efficacy against thrombotic complications, this comes on the expense of increased bleeding risk...
September 2016: Seminars in Thrombosis and Hemostasis
Amr F Barakat, Ayman A Hussein, Walid I Saliba, Mohammed Bassiouny, Khaldoun Tarakji, Mohamed Kanj, Wael Jaber, L Leonardo Rodriguez, Richard Grimm, M Shazam Hussain, Andrew Russman, Ken Uchino, Dolora Wisco, Peter Rasmussen, Mark Bain, John Vargo, Gregory Zuccaro, David Gottesman, Bruce D Lindsay, Oussama M Wazni
BACKGROUND: The implantation of left atrial appendage closure device (WATCHMAN, Boston Scientific, Natick, MA) is an alternative option to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation. Patients require short-term OAC after implantation to avoid device thrombosis. The 2 clinical trials that assessed this device excluded patients thought not to be candidates for OAC. As such, little is known about the safety of this strategy in patients with previous major bleeding events...
June 2016: Circulation. Arrhythmia and Electrophysiology
Huajie Zheng, Zeliang Wei, Guang Xin, Chengjie Ji, Li Wen, Qing Xia, Hai Niu, Wen Huang
Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregation in vitro. In the present study, we investigated the in vivo efficacy and safety of compound 5 using the ferric chloride (FeCl3)-induced arterial and venous thrombosis models in rats as well as its toxicity in mice...
July 15, 2016: Bioorganic & Medicinal Chemistry Letters
E V Roitman, I M Kolesnikova, I L Davydkin, N S Kozlova, S A Roumiantsev
INTRODUCTION: In today's antithrombotic prevention we forget that hemorheologic abnormalities are part of Virchow's triad. Isn't this one of reasons that venous thromboembolism (VTE) including catheter-related thrombosis (CRT) retain high frequency despite of modern antithrombotic therapy? AIM: The aim was to investigate rheological behavior of blood in patients with some myeloproliferative neoplasms. MATERIALS AND METHODS: The study included 16 adults with Polycythemia Vera (PV), 42 young with acute lymphoblastic leukemia (ALL), and 67 healthy donors as control group...
April 2016: Thrombosis Research
Travis Sexton, Eric L Wallace, Susan S Smyth
HMG CoA reductase inhibitors, or statins, are standard of care for preventing cardiovascular disease in at-risk populations. Statins are a well-established therapy proven to reduce long-term cardiovascular mortality and morbidity for prevention of secondary cardiovascular events and have become guideline-recommended therapy following acute myocardial infarction. Emerging data from clinical trials over the last decade indicates that statin therapy may provide broad beneficial effects beyond their primary lipid lowering mechanisms...
May 3, 2016: Current Cardiology Reviews
Álvaro Danza, Diego Graña, Mabel Goñi, Andrea Vargas, Guillermo Ruiz-Irastorza
Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile...
February 2016: Revista Médica de Chile
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