Genetic determinants of response to warfarin during initial anticoagulation.
Ute I. Schwarz,Marylyn D. Ritchie,Yuki Bradford,Chun Li,Scott M. Dudek,Amy Frye-Anderson,Richard B. Kim,Dan M. Roden,C. Michael Stein +8 more
TL;DR: Initial variability in the INR response to warfarin was more strongly associated with genetic variability inThe pharmacologic target of warfarIn, VKORC1, than with CYP2C9, and both of these genotypes had a significant influence on the required warfarins after the first 2 weeks of therapy.
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Abstract: Background Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses, but the role of these variants during initial anticoagulation is not clear. Methods In 297 patients starting warfarin therapy, we assessed CYP2C9 genotypes (CYP2C9 *1, *2, and *3), VKORC1 haplotypes (designated A and non-A), clinical characteristics, response to therapy (as determined by the international normalized ratio [INR]), and bleeding events. The study outcomes were the time to the first INR within the therapeutic range, the time to the first INR of more than 4, the time above the therapeutic INR range, the INR response over time, and the warfarin dose requirement. Results As compared with patients with the non-A/non-A haplotype, patients with the A/A haplotype of VKORC1 had a decreased time to the first INR within the therapeutic range (P=0...
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO)
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Paulus Kirchhof,Stefano Benussi,Dipak Kotecha,Anders Ahlsson,Dan Atar,Barbara Casadei,Manuel Castellá,Hans-Christoph Diener,Hein Heidbuchel,Jeroen M.L. Hendriks,Gerhard Hindricks,Antonis S. Manolis,Jonas Oldgren,Bogdan A. Popescu,Ulrich Schotten,Bart P. Van Putte,Panagiotis Vardas,Stefan Agewall,John Camm,Gonzalo Barón Esquivias,Werner Budts,Scipione Carerj,Filip Casselman,Antonio Coca,Raffaele De Caterina,Spiridon Deftereos,Dobromir Dobrev,José M. Ferro,Gerasimos Filippatos,Donna Fitzsimons,Bulent Gorenek,Maxine Guenoun,Stefan H. Hohnloser,Philippe Kolh,Gregory Y.H. Lip,Athanasios J. Manolis,John J.V. McMurray,Piotr Ponikowski,Raphael Rosenhek,Frank Ruschitzka,Irina Savelieva,Sanjay Sharma,Piotr Suwalski,Juan Tamargo,Clare J Taylor,Isabelle C. Van Gelder,Adriaan A. Voors,Stephan Windecker,José Luis Zamorano,Katja Zeppenfeld +49 more
TL;DR: The Task Force for the management of atrial fibrillation of the European Society of Cardiology has been endorsed by the European Stroke Organisation (ESO).
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESCEndorsed by the European Stroke Organisation (ESO)
Paulus Kirchhof,Stefano Benussi,Dipak Kotecha,Anders Ahlsson,Dan Atar,Barbara Casadei,Manuel Castellá,Hans-Christoph Diener,Hein Heidbuchel,Jeroen M.L. Hendriks,Gerhard Hindricks,Antonis S. Manolis,Jonas Oldgren,Bogdan A. Popescu,Ulrich Schotten,Bart P. van Putte,Panagiotis Vardas +16 more
TL;DR: Authors/Task Force Members: Paulus Kirchhof* (Chairperson) (UK/Germany), Stefano Benussi* (Co-Chair person) (Switzerland), Dipak Kotecha (UK), Anders Ahlsson (Sweden), Dan Atar (Norway), Barbara Casadei (UK)
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The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: Proposal for a new dosing regimen
Elizabeth Sconce,Tayyaba Khan,Tayyaba Khan,Hilary Wynne,Hilary Wynne,Peter Avery,Peter Avery,Louise Monkhouse,Louise Monkhouse,Barry P. King,Barry P. King,Peter Wood,Peter Wood,Patrick Kesteven,Patrick Kesteven,Ann K. Daly,Ann K. Daly,Farhad Kamali,Farhad Kamali +18 more
TL;DR: The multivariate regression model including the variables of age, CYP2C9 and VKORC1 genotype, and height produced the best model for estimating warfarin dose (R2 = 55%).
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Comparison of Low-Intensity Warfarin Therapy with Conventional-Intensity Warfarin Therapy for Long-Term Prevention of Recurrent Venous Thromboembolism
Clive Kearon,Jeffrey S. Ginsberg,Michael J. Kovacs,David R. Anderson,Philip S. Wells,Jim A. Julian,Betsy MacKinnon,Jeffrey I. Weitz,Mark Crowther,Sean Dolan,Alexander G.G. Turpie,William H. Geerts,Susan Solymoss,Paul Van Nguyen,Christine Demers,Susan R. Kahn,Jeannine Kassis,Marc A. Rodger,Julie Hambleton,Michael Gent +19 more
TL;DR: Conventional- intensity warfarin therapy is more effective than low-intensity warFarin therapy for the long-term prevention of recurrent venous thromboembolism and the low- intensity regimen does not reduce the risk of clinically important bleeding.
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A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin.
Giovanna D'Andrea,Rosa Lucia D'Ambrosio,Rosa Lucia D'Ambrosio,Pasquale Di Perna,Pasquale Di Perna,Massimiliano Chetta,Massimiliano Chetta,Rosa Santacroce,Rosa Santacroce,Vincenzo Brancaccio,Vincenzo Brancaccio,Elvira Grandone,Elvira Grandone,Maurizio Margaglione,Maurizio Margaglione +14 more
TL;DR: Genetic variants of the VKORC1 gene locus modulate the mean daily dose of drug prescribed to acquire the target anticoagulation intensity and accounted for about a third of the interindividual variability in the present setting.
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A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. A randomized, controlled trial.
TL;DR: In this paper, a multicomponent comprehensive program of warfarin management reduced the frequency of major bleeding in older patients, including patient education, training to increase patient participation, self-monitoring of prothrombin time, and guideline-based management of dosing.
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Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin.
Brian F. Gage,Charles S. Eby,Paul E. Milligan,Gerald A. Banet,Jill R. Duncan,Howard L. McLeod +5 more
TL;DR: The maintenance warfarin dose can be estimated from demographic, clinical, and pharmacogenetic factors that can be obtained at the time ofwarfarin initiation, and has potential to prevent patients from being overdosed.
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