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https://www.readbyqxmd.com/read/28198201/clinical-implications-of-reversal-agents-for-direct-oral-anticoagulants
#1
Sarah Monagle, John W Eikelboom, Kuan H Ng, Vinai C Bhagirath
Direct oral anticoagulants (DOACs) are effective in preventing and treating venous thromboembolism, and preventing stroke in atrial fibrillation. Until recently, there has been no specific reversal agent for DOACs. Now, a specific antidote for the direct thrombin inhibitor, dabigatran has been approved for use, and antidotes for factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are being developed. We review the evidence for currently used and emerging reversal strategies, and discuss possible clinical implications, including increased prescription of DOACs, use of DOACs in clinical situations previously felt to pose too great a risk of bleeding, and use of reversal agents beyond currently approved indications...
March 2017: Future Cardiology
https://www.readbyqxmd.com/read/28196633/old-and-new-oral-anticoagulants-food-herbal-medicines-and-drug-interactions
#2
REVIEW
Alessandro Di Minno, Beatrice Frigerio, Gaia Spadarella, Alessio Ravani, Daniela Sansaro, Mauro Amato, Joseph P Kitzmiller, Mauro Pepi, Elena Tremoli, Damiano Baldassarre
The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs...
February 5, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28191610/italian-intersociety-consensus-on-doac-use-in-internal-medicine
#3
Domenico Prisco, Walter Ageno, Cecilia Becattini, Armando D'Angelo, Giovanni Davì, Raimondo De Cristofaro, Francesco Dentali, Giovanni Di Minno, Anna Falanga, Gualberto Gussoni, Luca Masotti, Gualtiero Palareti, Pasquale Pignatelli, Roberto M Santi, Francesca Santilli, Mauro Silingardi, Antonella Tufano, Francesco Violi
The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events...
February 13, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28185082/dabigatran-etexilate-a-review-in-nonvalvular-atrial-fibrillation
#4
Hannah A Blair, Gillian M Keating
Dabigatran etexilate (Pradaxa(®)) is approved in the EU for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) and one or more risk factors. Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. In patients with NVAF in the phase III RE-LY trial, dabigatran etexilate dosages of 110 and 150 mg twice daily were noninferior to warfarin with regard to the risk of stroke or systemic embolism (primary efficacy endpoint). The higher dosage was associated with a significantly lower risk of stroke or systemic embolism than warfarin, with no significant between-group difference in the risk of major bleeding (primary safety endpoint)...
February 9, 2017: Drugs
https://www.readbyqxmd.com/read/28169097/evaluation-of-the-efficacy-and-safety-of-direct-oral-anticoagulants-in-japanese-patients-analysis-of-pharmaceuticals-and-medical-devices-agency-data
#5
Yasuo Terayama
BACKGROUND: Two forms of direct oral anticoagulant (DOAC) have recently been introduced: direct thrombin inhibitors (DTI; e.g., dabigatran) and factor Xa inhibitors (FXa; e.g., rivaroxaban and apixaban). Despite the advantages of DOACs over warfarin with regard to cerebrovascular complications, those associated with DOACs have been reported with the increasing use of DOACs. Nevertheless, little is known about real-world comparative efficacy and safety of DOACs. METHODS: Cerebrovascular adverse events collected by the Pharmaceutical and Medical Devices Agency (PMDA) during 2014 were analyzed to describe and compare efficacy and safety among patients prescribed DTI and FXa...
February 3, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28043992/direct-oral-anticoagulants-and-heparins-laboratory-values-and-pitfalls-in-bridging-therapy
#6
Thomas Eller, Tobias Flieder, Vanessa Fox, Tatjana Gripp, Marcus Dittrich, Joachim Kuhn, Susanne Alban, Cornelius Knabbe, Ingvild Birschmann
OBJECTIVES: The three direct oral anticoagulants (DOACs) dabigatran, apixaban and rivaroxaban are now widely used in clinical practice. For patients requiring perioperative interruption of DOACs, heparin bridging is still under discussion. Here we show, for the first time, the influence of concomitantly used DOACs and heparins on laboratory assays. METHODS: For spiking experiments, 10 healthy donors and nine patients treated with DOACs were investigated. The measurement of DOACs and heparins was performed with routine methods on the ACL TOP [HEMOCLOT(®) direct thrombin inhibitor (CoaChrom Diagnostica, Austria), COAMATIC(®) Heparin (Chromogenix, USA) calibrated with rivaroxaban, apixaban, unfractionated heparin (UFH) and low molecular weight heparin (LMWH), additionally PT reagent RecombiPlasTin 2G and aPTT reagent SynthASil (Instrumentation Laboratory, Germany)] and the DOACs were additionally quantified with liquid chromatography-mass spectrometry...
January 2, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28042443/differences-between-warfarin-and-new-oral-anticoagulants-in-dental-clinical-practice
#7
REVIEW
M Miranda, L S Martinez, R Franco, V Forte, A Barlattani, P Bollero
The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant - dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) - have been approved for use in europe...
July 2016: Oral & Implantology
https://www.readbyqxmd.com/read/28029411/atrial-fibrillation-and-heart-failure-factors-influencing-the-choice-of-oral-anticoagulant
#8
REVIEW
Louise A E Brown, Christopher J Boos
Atrial fibrillation (AF) and heart failure (HF) frequently coexist. AF is identified in approximately one third of patients with HF and is linked to increased morbidity and mortality than from either condition alone. AF is relatively more common in HF with preserved ejection fraction (HFpEF) than with reduced ejection fraction (HFrEF). Nevertheless, the risk of stroke and systemic embolism (SSE) is significantly increased with both HF types and the absolute risk is heavily influenced by the presence and severity of associated additional stroke risk factors...
September 30, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28011314/idarucizumab-praxbind%C3%A2-the-first-reversal-agent-for-a-direct-oral-anticoagulant
#9
EDITORIAL
Shannon W Finks, Kelly C Rogers
Idarucizumab is a humanized monoclonal antibody fragment engineered to specifically neutralize the effects of the oral direct thrombin inhibitor dabigatran in order to restore hemostasis. FDA approval for idarucizumab, under the brand name Praxbind®, was granted in October 2015 for the reversal of dabigatran in settings of emergent life-threatening bleeding episodes or in the case when an emergent surgery or urgent procedure is needed to reverse its anticoagulant effects.(1) This article summarizes pertinent and clinical information regarding idarucizumab and other reversal agents currently under investigation...
December 20, 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/28000559/in-models-of-intracerebral-hemorrhage-rivaroxaban-is-superior-to-warfarin-to-limit-blood-brain-barrier-disruption-and-hematoma-expansion
#10
Shigenobu Sawada, Yoko Ono, Yusuke Egashira, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Intracerebral hemorrhage (ICH) during oral anticoagulation therapy with an oral vitamin K epoxidase reductase such as warfarin is a life-threatening complication. However, whether direct oral anticoagulants (DOACs) are associated with larger hematoma volume and higher mortality rates remains controversial. We evaluated the hematoma volume and pathophysiology of ICH during anticoagulation with warfarin or rivaroxaban, an orally active direct factor Xa inhibitor. Mice were orally pretreated with rivaroxaban (10 or 30 mg/kg), warfarin (4 mg/kg), or vehicle...
December 16, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27993122/in-models-of-intracerebral-hemorrhage-rivaroxaban-is-superior-to-warfarin-to-limit-blood-brain-barrier-disruption-and-hematoma-expansion
#11
Shigenobu Sawada, Yoko Ono, Yusuke Egashira, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Intracerebral hemorrhage (ICH) during oral anticoagulation therapy with an oral vitamin K epoxidase reductase such as warfarin is a life-threatening complication. However, whether direct oral anticoagulants (DOACs) are associated with larger hematoma volume and higher mortality rates remains controversial. We evaluated the hematoma volume and pathophysiology of ICH during anticoagulation with warfarin or rivaroxaban, an orally active direct factor Xa inhibitor. Mice were orally pretreated with rivaroxaban (10 or 30 mg/kg), warfarin (4 mg/kg), or vehicle...
December 16, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27992120/dabigatran-enhances-platelet-reactivity-and-platelet-thrombin-receptor-expression-in-patients-with-atrial-fibrillation
#12
A Achilles, A Mohring, L Dannenberg, M Grandoch, T Hohlfeld, J W Fischer, B Levkau, M Kelm, T Zeus, A Polzin
: Essentials Whether or not dabigatran enhances the risk of myocardial infarction is under discussion. We measured platelet reactivity and thrombin receptor expression in dabigatran patients. Platelet reactivity and thrombin receptor expression is enhanced during dabigatran treatment. This should be considered when choosing the optimal direct oral anticoagulant for individuals. SUMMARY: Background The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor...
December 19, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27929577/a-practical-approach-to-the-new-oral-anticoagulants-used-for-stroke-prevention-in-patients-with-atrial-fibrillation
#13
S Bashir, A Al-Mohammed, S Gupta
This review evaluates the research undertaken in the last six years on the use of new oral anticoagulants for stroke prevention in atrial fibrillation and provides evidence-based answers to common clinical questions. Two types of new oral anticoagulants - direct thrombin (IIa) inhibitors, and Xa inhibitors - are currently available. These drugs have similar pharmacokinetics and pharmacodynamics. They are more predictable than, though in many respects comparable to, warfarin. They do not require frequent laboratory tests, nor do they have a narrow therapeutic window...
June 2016: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/27917715/antiplatelet-agents-and-anticoagulants-in-patients-with-chronic-kidney-disease-from-pathophysiology-to-clinical-practice
#14
Jens Lutz, Kerstin Jurk
Progressive impairment of renal function can lead to uremia, which is associated with thus increasing the risk of bleeding as well as thrombosis. Furthermore, many patients with chronic kidney disease (CKD) have an indication for an anticoagulation or antiplatelet therapy due to atrial fibrillation, coronary artery disease, thromboembolic disease, or peripheral artery disease. The treatment usually includes vitamin-K antagonists (VKAs) and/or platelet aggregation inhibitors. The direct oral anticoagulants (DOACs) inhibiting factor Xa or thrombin activity represent an alternative for heparins and VKAs...
December 5, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#15
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910004/dabigatran-overdose-a-case-report-of-acute-hepatitis-extracorporeal-treatment
#16
Mariagrazia Porru, Antonella Mameli, Maria E Cianchetti, Mario Musu, Paola Schirru, Maria F Ruberto, Doris Barcellona, Francesco Marongiu
Dabigatran is an oral, direct thrombin inhibitor approved by international regulatory agencies for stroke prevention in patients with paroxysmal or persistent non-rheumatic atrial fibrillation (AF). The benefits of dabigatran are widely described, but its use in the geriatric population is not without risk. Chronic kidney disease is a common comorbidity with AF, and thus frequent checks of renal function in elderly patients are recommended. We report a case of dabigatran intoxication in an elderly man affected by heart failure and worsening renal function, who developed acute hepatitis and coma, which was successfully treated with continuous veno-venous hemodiafiltration...
December 1, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27909544/reducing-the-risk-of-stroke-in-patients-with-nonvalvular-atrial-fibrillation-with-direct-oral-anticoagulants-is-one-of-these-not-like-the-others
#17
REVIEW
Paul P Dobesh Pharm D, John Fanikos Mba R Ph
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases risk of stroke by nearly 5-fold. While warfarin has been employed successfully to reduce the risk of stroke in these patients, there are a number of challenges with therapy. These include the need for therapeutic monitoring due to variability in patient response, frequent dose adjustments, numerous drug-drug, drug-food, and drug-disease interactions, and a heightened risk of thrombosis and bleeding due to these issues. Current guidelines recommend that the vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27901390/effects-of-various-antiplatelet-drugs-on-ex-vivo-platelet-activation-induced-by-equine-herpesvirus-type-1
#18
RANDOMIZED CONTROLLED TRIAL
Daniela Hernandez, Wee Ming Yeo, Marjory B Brooks, Sally L Ness, Thomas J Divers, Tracy Stokol
OBJECTIVE To evaluate the effects of treatment of horses with standard platelet inhibitors on ex vivo inhibition of platelet activation by equine herpesvirus type I (EHV-I). ANIMALS II healthy adult horses. PROCEDURES In a double-blinded, placebo-controlled crossover study, horses were treated orally for 5 days with theophylline (5 mg/kg, q 12 h), pentoxifylline (10 mg/kg, q 12 h), clopidogrel bisulfate (4 mg/kg, q 24 h), acetylsalicylic acid (20 mg/kg, q 24 h), or placebo. Horses received all treatments, each separated by a 3-week washout period...
December 2016: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/27900867/-new-direct-oral-anticoagulants-actual-review
#19
Jana Michalcová, Miroslav Penka, Alena Buliková, Jiřina Zavřelová, Andrea Štěpařová
In recent years the options of anticoagulant/antithrombotic therapy have extended with new - direct oral anticoagulants, comprising direct thrombin inhibitors (dabigatran etexilate) and direct factor Xa inhibitors (rivaroxaban, apixaban). These agents represent another progress towards "the ideal antithrombotic drug", and thus towards a safe and effective antithrombotic therapy. The following article provides actual review and recommendations for clinical practice, including laboratory assessment and management of emergency situations...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27896543/vitamin-k-antagonists-relative-strengths-and-weaknesses-vs-direct-oral-anticoagulants-for-stroke-prevention-in-patients-with-atrial-fibrillation
#20
REVIEW
Andreas Zirlik, Christoph Bode
Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for more than 50 years. VKAs are mainly used for the prevention of stroke in patients with atrial fibrillation (AF) and the treatment and secondary prevention of venous thromboembolism. In the past 5 years, four new agents-the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or non-VKA oral anticoagulants]-have been approved for these and other indications...
November 28, 2016: Journal of Thrombosis and Thrombolysis
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