Personalized approach for direct oral anticoagulant prescription: from theory to practice


Cite item

Full Text

Abstract

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

About the authors

A I Skripka

Sechenov First Moscow State Medical University (Sechenov University)

аспирант каф. факультетской терапии №1 Института клинической медицины ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет) Moscow, Russia

V V Kogay

Sechenov First Moscow State Medical University (Sechenov University)

студентка VI курса Международной школы «Медицина будущего» научно-технологического парка биомедицины ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет) Moscow, Russia

A I Listratov

Sechenov First Moscow State Medical University (Sechenov University)

студент VI курса Международной школы «Медицина будущего» научно-технологического парка биомедицины ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет) Moscow, Russia

A A Sokolova

Sechenov First Moscow State Medical University (Sechenov University)

к.м.н., ассистент каф. факультетской терапии № 1 Института клинической медицины ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет) Moscow, Russia

D A Napalkov

Sechenov First Moscow State Medical University (Sechenov University)

Email: dminap@mail.ru
д.м.н., проф. каф. факультетской терапии № 1 Института клинической медицины ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет) Moscow, Russia

V V Fomin

Sechenov First Moscow State Medical University (Sechenov University)

д.м.н., проф., член-корр. РАН, зав. каф. факультетской терапии №1 Института клинической медицины ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет) Moscow, Russia

References

  1. Сычев Д.А., Игнатьев И.В., Емельянов Н.В., Савельева М.И., Дмитриев В.А., Кукес В.Г., Герасимова К.В. Фармакогенетическое тестирование: первые шаги в реальной клинической практике и проблемы стандартизации. Проблемы стандартизации в здравоохранении. 2009;1:43-55.
  2. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener H.C, Heidbuchel H, Hendriks J, Hindricks G, Manolis A.S, Oldgren J, Popescu B.A, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro J.M, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser S.H, Kolh P, Lip G.Y, Manolis A, Mc Murray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo J.L, Taylor C.J, Van Gelder I.C, Voors A.A, Windecker S, Zamorano J.L, Zeppenfeld K. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016;18(11):2893-962. doi: 10.1093/europace/euw295
  3. Инструкция по применению лекарственного препарата Прадакса. Государственный реестр лекарственных средств. Доступно по: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=e4817690-bf14-4e4e-9562-256d415636c7&t=. Ссылка активна на 25.10.2018.
  4. Reilly P.A, Lehr T, Haertter S, Connolly S.J, Yusuf S, Eikelboom J.W, Ezekowitz M.D, Nehmiz G, Wang S, Wallentin L. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014 Feb 4;63(4):321-8. doi: 10.1016/j.jacc.2013.07.104
  5. Ezekowitz M.D, Connolly S, Parekh A, Reilly P.A, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S. Rationale and design of RE-LY: randomized evaluation of long - term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J. 2009 May;157(5):805-10.e1-2. doi: 10.1016/j.ahj.2009.02.005
  6. Paré G, Eriksson N, Lehr T, Connolly S, Eikelboom J, Ezekowitz M.D, Axelsson T, Haertter S, Oldgren J, Reilly P, Siegbahn A, Syvanen A.C, Wadelius C, Wadelius M, Zimdahl-Gelling H, Yusuf S, Wallentin L. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013 Apr 2;127(13):1404-12. doi: 10.1161/CIR CULATIONAHA.112.001233
  7. Testa S, Tripodi A, Legnani C, Pengo V, Abbate R, Dellanoce C, Carraro P, Salomone L, Paniccia R, Paoletti O, Poli D, Palareti G. Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics. Thromb Res. 2016 Jan;137:178-83. doi: 10.1016/j.thromres.2015.12.001
  8. Pharm GKB. Available at: https://www.pharmgkb.org/chemical/PA1651 10351/clinicalAnnotation. Accessed October 24, 2018.
  9. Merali Z, Ross S, Paré G. The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect. Drug Metabol Drug Interact. 2014;29(3):143-51. doi: 10.1515/dmdi-2014-0009
  10. Dimatteo C, D'Andrea G, Vecchione G, Paoletti O, Cappucci F, Tiscia G.L, Buono M, Grandone E, Testa S, Margaglione M. Pharmacogenetics of dabigatran etexilate interindividual variability. Thromb Res. 2016 Aug; 144:1-5. doi: 10.1016/j.thromres.2016.05.025
  11. Мещеряков Ю.В., Чертовских Я.В., Сычёв Д.А. Фармакогенетика нового орального антикоагулянта дабигатрана - роль полиморфизма rs2244613 CES1 в развитии нежелательных побочных реакций. Фармакогенетика и фармакогеномика. 2017;2:18-9.
  12. Сычев Д.А., Казаков Р.Е., Отделенов В.А., Прокофьев А.Б. Прикладные аспекты применения фармакогенетического тестирования для персонализации применения пероральных антикоагулянтов в российских условиях. Рациональная фармакотерапия в кардиологии. 2013;9(5):525-31. doi: 10.20996/1819-6446-2013-9-5-525-531
  13. Kreutz R. Pharmacodynamic and pharmacokinetic basics of rivaroxaban. Fundam Clin Pharmacol. 2011;26(1):27-32. doi: 10.1111/j.1472-8206. 2011.00981.x
  14. Kubitza D, Becka M, Roth A, Mueck W. The Influence of Age and Gender on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban-An Oral, Direct Factor Xa Inhibitor. J Clin Pharmacol. 2013;53(3):249-55. doi: 10.1002/jcph.5
  15. Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Body Weight Has Limited Influence on the Safety, Tolerability, Pharmacokinetics, or Pharmacodynamics of Rivaroxaban (BAY 59-7939) in Healthy Subjects. J Clini Pharmacol. 2007;47(2):218-26. doi: 10.1177/009127000626058
  16. Инструкция по применению лекарственного препарата Ксарелто. Государственный реестр лекарственных средств. Доступно по: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=732bced6-0374-4deb-a882-c6745d527c8d&t=. Ссылка активна на 24.10.2018.
  17. Kubitza D, Roth A, Becka M, Alatrach A, Halabi A, Hinrichsen H, Mueck W. Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2013;76(1):89-98. doi: 10.1111/bcp.12054
  18. Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Rivaroxaban (BAY 59-7939) an oral, direct Factor Xa inhibitor has no clinically relevant interaction with naproxen. Br J Clin Pharmacol. 2007;63(4):469-76. doi: 10.1111/j.1365-2125.2006.02776.x
  19. Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Rivaroxaban-an Oral, Direct Factor Xa Inhibitor-Are Not Affected by Aspirin. J Clin Pharmacol. 2006;46(9):981-90. doi: 10.1177/0091270006292127
  20. Kubitza D, Becka M, Mück W, Schwers S. Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study. Pharmaceuticals. 2012;5(3):279-96. doi: 10.3390/ph5030279
  21. Kubitza D, Becka M, Schwers S, Voith B. Investigation of Pharmacodynamic and Pharmacokinetic Interactions Between Rivaroxaban and Enoxaparin in Healthy Male Subjects. Clin Pharmacol Drug Dev. 2013;2(3):270-7. doi: 10.1002/cpdd.26
  22. Kubitza D, Becka M, Mück W, Krätzschmar J. Pharmacodynamics and pharmacokinetics during the transition from warfarin to rivaroxaban: a randomized study in healthy subjects. Br J Clin Pharmacol. 2014;78(2):353-63. doi: 10.1111/bcp.12349
  23. Kubitza D, Becka M, Roth A, Mueck W. Absence of Clinically Relevant Interactions between Rivaroxaban - an Oral, Direct Factor Xa Inhibitor - and Digoxin or Atorvastatin in Healthy Subjects. J International Med Research. 2012;40(5):1688-707. doi: 10.1177/03000 6051204000508
  24. Mueck W, Kubitza D, Becka M. Co - administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455-66. doi: 10.1111/ bcp.12075
  25. Maier C, Duncan A, Hill C. Pharmacogenetics in Oral Antithrombotic Therapy. Clin Lab Med. 2016;36(3):461-72. doi: 10.1016/j.cll.2016.05. 002
  26. Sychev D.A, Vardanyan A, Rozhkov A, Hachatryan E, Badanyan A, Smirnov V, Ananichuk A, Denisenko N. CYP3A Activity and Rivaroxaban Serum Concentrations in Russian Patients with Deep Vein Thrombosis. Genet Test Mol Biomarkers. 2018 Jan;22(1):51-4. doi: 10.1089/gtmb.2017.0152
  27. Gouin-Thibault I, Delavenne X, Blanchard A, Siguret V, Salem J.E, Narjoz C, Gaussem P, Beaune P, Funck-Brentano C, Azizi M, Mismetti P, Loriot M.A. Interindividual variability in dabigatran and rivaroxaban exposure: contribution of ABCB1 genetic polymorphisms and interaction with clarithromycin. J Thrombosis and Haemostasis. 2017;15(2):273-83. doi: 10.1111/jth.1357
  28. Крюков А.В., Сычев Д.А., Терещенко О.В. Фармакогенетические аспекты применения новых оральных антикоагулянтов. Рациональная фармакотерапия в кардиологии. 2017;13(3):416-21. doi: 10.20996/1819-6446-2017-13-3-416-421
  29. Ing Lorenzini K, Daali Y, Fontana P, Desmeules J, Samer C. Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect. Front Pharmacol. 2016;7. doi: 10.3389/fphar.2016.00494
  30. Dideriksen D, Damkier P, Nybo M. Rivaroxaban non - responders: do plasma measurements have a place? Clinical Chemistry and Laboratory Medicine (CCLM). 2017;56(1). doi: 10.1515/cclm-2017-0473
  31. Ameyaw M.M, Regateiro F, Li T, Liu X, Tariq M, Mobarek A, Thornton N, Folayan G.O, Githang'a J, Indalo A, Ofori-Adjei D, Price-Evans D.A, Mc Leod H.L. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics. 2001;11(3):217-21. doi: 10.1097/00008571-2001040 00-00005
  32. Инструкция по применению лекарственного препарата Леветирацетам. Государственный реестр лекарственных средств. Доступно по https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routing Guid= 7277294a-54eb-4b9f-9ebd-9bed37cccfee&t= Ссылка активна на 24.10.2018.
  33. Stöllberger C, Finsterer J. Interactions between non - vitamin K oral anticoagulants and antiepileptic drugs. Epilepsy Res. 2016;126:98-101. doi: 10.1016/j.eplepsyres.2016.06.003
  34. Gnoth M, Buetehorn U, Muenster U, Schwarz T, Sandmann S. In Vitro and In Vivo P-Glycoprotein Transport Characteristics of Rivaroxaban. J Pharmacology and Experimental Therapeutics. 2011;338(1):372-80. doi: 10.1124/jpet.111.180240
  35. Cusatis G, Gregorc V, Li J, Spreafico A, Ingersoll R.G, Verweij J, Ludovini V, Villa E, Hidalgo M, Sparreboom A, Baker S.D. Pharmacogenetics of ABCG2 and Adverse Reactions to Gefitinib. JNCI: J National Cancer Institute. 2006;98(23):1739-42. doi: 10.1093/jnci/ djj469
  36. Gong I, Mansell S, Kim R. Absence of both MDR1 (ABCB1) and Breast Cancer Resistance Protein (ABCG2) Transporters Significantly Alters Rivaroxaban Disposition and Central Nervous System Entry. Basic Clin Pharmacol Toxicol. 2012;112(3):164-70. doi: 10.1111/bcpt.12005
  37. Sim S, Ingelman-Sundberg M. The Human Cytochrome P450 (CYP) Allele Nomenclature website: a peer - reviewed database of CYP variants and their associated effects. Hum Genomics. 2010;4(4):278. doi: 10.1186/1479-7364-4-4-278
  38. O’Connor C, Kiernan T, Yan B. The genetic basis of antiplatelet and anticoagulant therapy: A pharmacogenetic review of newer antiplatelets (clopidogrel, prasugrel and ticagrelor) and anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban). Expert Opin Drug Metab Toxicol. 2017;13(7):725-39. doi: 10.1080/17425255.2017.1338274
  39. Инструкция по применению лекарственного препарата Эликвис. Государственный реестр лекарственных средств. Доступно по: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=b0cb1df0-3494-4405-88fd-78b9995872fd&t= Ссылка активна на 24.10.2018.
  40. Granger C.B, Alexander J.H, Mc Murray J.J, Lopes R.D, Hylek E.M, Hanna M, Al-Khalidi H.R, Ansell J, Atar D, Avezum A, Bahit M.C, Diaz R, Easton J.D, Ezekowitz J.A, Flaker G, Garcia D, Geraldes M, Gersh B.J, Golitsyn S, Goto S, Hermosillo A.G, Hohnloser S.H, Horowitz J, Mohan P, Jansky P, Lewis B.S, Lopez-Sendon J.L, Pais P, Parkhomenko A, Verheugt F.W, Zhu J, Wallentin L. ARISTOTLE Committees and Investigators. Committees and Investigators: apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2011 Sep;365:981-92. doi: 10.1056/NEJMoa1107039
  41. Connolly S.J, Eikelboom J, Joyner C, Diener H.C, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser S.H, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan R.S, Sim K.H, Lewis B.S, Van Mieghem W, Lip G.Y, Kim J.H, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans A.L, Munawar M, O'Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban in Patients with Atrial Fibrillation. N Engl J Med. 2011;364:806-17. doi: 10.1056/NEJMoa1007432
  42. Frost C.E, Song Y, Shenker A, Wang J, Barrett Y.C, Schuster A, Harris S.I, La Creta F. Effects of age and sex on the single - dose pharmacokinetics and pharmacodynamics of apixaban. Clin Pharmacokinet. 2015 Jun;54(6):651-62. doi: 10.1007/s40262-014-0228-0
  43. Chang M, Yu Z, Shenker A. Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. J Clin Pharmacol. 2016 May;56(5):637-45. doi: 10.1002/jcph.633
  44. Mavrakanas T.A, Samer C.F, Nessim S.J. Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients. J Am Soc Nephrol. 2017 Jul;28(7):2241-8. doi: 10.1681/ASN.2016090980
  45. Di Minno A, Frigerio B, Spadarella G. Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Blood Rev. 2017 Jul;31(4):193-203. doi: 10.1016/j.blre.2017.02.001
  46. Kryukov A.V, Sychev D.A, Andreev D.A, Ryabova A.V, Denisenko N.P, Loskutnikov M.A, Vinogradov O.I, Domashenko M.A. The pharmacokinetics of apixaban in patients with cardioembolic stroke in acute phase. Ration Pharmacother Cardiol. 2016;12(3):253-9. doi: 10.20996/1819-6446-2016-12-3-253-259
  47. Wang L, Zhang D, Raghavan N, Yao M, Ma L, Frost C.E, Maxwell B.D, Chen S.Y, He K, Goosen T.C, Humphreys W.G, Grossman S.J. In Vitro Assessment of Metabolic Drug-Drug Interaction Potential of Apixaban through Cytochrome P450 Phenotyping, Inhibition, and Induction Studies. Drug Metab Dispos. 2010;38:448-58. doi: 10.1124/dmd.109. 029694
  48. Kryukov A.V, Sychev D.A, Andreev D.A, Ryzhikova K.A, Grishina E.A, Ryabova A.V, Loskutnikov M.A, Smirnov V.V, Konova O.D, Matsneva I.A, Bochkov P.O. Influence of ABCB1 and CYP3A5 gene polymorphisms on pharmacokinetics of apixaban in patients with atrial fibrillation and acute stroke. Pharmgenomics Pers Med. 2018 Mar 22;11:43-9. doi: 10.2147/ PGPM.S157111
  49. Zhang D, He K, Herbst J.J, Kolb J, Shou W, Wang L, Balimane P.V, Han Y.H, Gan J, Frost C.E, Humphreys W.G. Characterization of Efflux Transporters Involved in Distribution and Disposition of Apixaban. Drug Metab Dispos. 2013 Apr;41:827-35. doi: 10.1124/dmd.112.050260
  50. Dimatteo C, D'Andrea G, Vecchione G. ABCB1 SNP rs4148738 modulation of apixaban interindividual variability. Thromb Res. 2016 Sep;145:24-6. doi: 10.1016/j.thromres.2016.07.005
  51. Ueshima S, Hirab D, Fujii R. Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation. Pharmacogenet Genomics. 2017 Sep;27(9):329-36. doi: 10.1097/FPC.0000000000000294
  52. Weitz J.I, Connolly S.J, Patel I, Salazar D, Rohatagi S, Mendell J, Kastrissios H, Jin J, Kunitada S. Randomised, parallel - group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost. 2010;104:633-41. doi: 10.1160/TH10-01-0066
  53. Giugliano R.P, Ruff C.T, Braunwald E, Murphy S.A, Wiviott S.D, Halperin J.L, Waldo A.L, Ezekowitz M.D, Weitz J.I, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip L.T, Patel S.P, Patel I, Hanyok J.J, Mercuri M, Antman E.M; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2013;369:2093-104. doi: 10.1056/NEJMoa1310907
  54. Mendell J, Johnson L, Chen S. An open - label, phase 1 study to evaluate the effects of hepatic impairment on edoxaban pharmacokinetics and pharmacodynamics. J Clin Pharmacol. 2015 Dec;55(12):1395-405. doi: 10.1002/jcph.550
  55. Parasrampuria D.A, Truitt K.E. Pharmacokinetics and pharmacodynamics of edoxaban, a non - vitamin K antagonist oral anticoagulant that inhibits clotting factor Xa. Clin Pharmacokinet. 2016 Jun;55(6):641-55. doi: 10.1007/s40262-015-0342-7
  56. Koretsune Y, Yamashita T, Kimura T, Fukuzawa M, Abe K, Yasaka M. Short-Term Safety and Plasma Concentrations of Edoxaban in Japanese Patients With Non-Valvular Atrial Fibrillation and Severe Renal Impairment. Circ J. 2015;79(7):1486-95. doi: 10.1253/circj.CJ-14-0942
  57. Mendell J, Zahir H, Matsushima N, Noveck R, Lee F, Chen S, Zhang G, Shi M. Drug - drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor. Am J Cardiovasc Drugs. 2013 Oct;13(5):331-42. doi: 10.1007/s40256-013-0029-0
  58. Mega J.L, Walker J.R, Ruff C.T, Vandell A.G, Nordio F, Deenadayalu N, Murphy S.A, Lee J, Mercuri M.F, Giugliano R.P, Antman E.M, Braunwald E, Sabatine M.S. Genetics and the clinical response to warfarin and edoxaban: findings from the randomised, double - blind ENGAGE AF-TIMI 48 trial. Lancet. 2015 Jun 6;385(9984):2280-7. doi: 10.1016/S0140-6736(14)61994-2
  59. Vandell A.G, Walker J, Brown K.S, Zhang G, Lin M, Grosso M.A, Mercuri M.F. Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism. Heart. 2017 Nov;103(22):1800-5. doi: 10.1136/heartjnl-2016-310901
  60. Vandell A.G, Lee J, Shi M, Rubets I, Brown K.S, Walker J.R. An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure. Pharmacogenomics J. 2018 Jan;18(1):153-9. doi: 10.1038/tpj.2016.82
  61. Savaysa (edoxaban) tablets [prescribing information]. Parisippany, NJ: Daiichi Sankyo, Inc; 2015. Available at: https://savaysahcp.com/nvaf-safety-and-efficacy. Accessed October 24, 2018.
  62. Сайт для расчета дозировки варфарина [Электронный ресурс] Доступно по: http://warfarindosing.org/Source/Home.aspx. Ссылка активна на 10.06.2019.

Copyright (c) 2019 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies