2015


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2015/№6

Клинико-фармакологические аспекты применения новых оральных антикоагулянтов у пациентов с фибрилляцией предсердий

Сычев Д. А., Крюков А. В., Савельева М. И., Рябова А. В., Цомая И. В.
ГБОУ ДПО «РМАПО» МЗ РФ, 123995, Москва, ул. Баррикадная, д. 2 / 1

Ключевые слова: антикоагулянты, ривароксабан, дабигатран, апиксабан, эдоксабан, фармакокинетика, фармакодинамика, клинические исследования, комплаентность

DOI: 10.18087/rhj.2015.6.2139

В обзоре обсуждаются особенности фармакокинетики новых оральных антикоагулянтов (НОАК) – дабигатрана, ривароксабана, апиксабана и эдоксабана, принципы выбора режимов дозирования этих препаратов для клинических исследований III фазы у больных с фибрилляцией предсердий (ФП), практические аспекты применения, коррекции дозы препаратов в зависимости от профиля пациента, подходы к персонализированному выбору антикоагулянтов. Показано, что кратность применения НОАК может быть обусловлена необходимым уровнем антикоагуляции, длительностью действия, взаимосвязью между минимальной и максимальной равновесными концентрациями и эффективностью и безопасностью. Применение некоторых антикоагулянтов один раз в сутки может обеспечить не только лучшую приверженность к лечению, но и снижение риска развития кровотечений. Результаты исследований НОАК в реальной клинической практике демонстрируют высокий уровень комплаентности при однократном режиме дозирования. Учитывая тот факт, что количество кровотечений в реальной практике не превышает показатели клинических исследований, вполне правомерно обратить особое внимание на важность приверженности пациентов к лечению для безопасности антикоагулянтной терапии.
  1. Stewart S, Hart CL, Hole DJ, McMurray JJ. Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew / Paisley study. Heart. 2001 Nov;86 (5):516–21.
  2. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285 (18):2370–5.
  3. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006 Jul 11;114 (2):119–25.
  4. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricer BH et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006 Apr;27 (8):949–53.
  5. Naccarelli GV, Varker H, Lin J, Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol. 2009 Dec 1;104 (11):1534–9.
  6. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS et al. Life­time risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004 Aug 31;110 (9):1042–6.
  7. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991 Aug;22 (8):983–8.
  8. Сулимов В. А., Напалков Д. А., Соколова А. А. Сравнительная эффективность и безопасность новых пероральных антикоагулянтов. Рациональная фармакотерапия в кардиологии. 2013;9 (4):433–8.
  9. Heidbuchel H, Verhamme P, Alings M, Antz M, Hack W, Oldgren J et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013 May;15 (5):625–51.
  10. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361 (12):1139–51.
  11. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365 (10):883–91.
  12. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365 (11):981–92.
  13. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3;364 (9):806–17.
  14. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369 (22):2093–104.
  15. Renda G, De Caterina R. The new oral anticoagulants in atrial fibrillation: once daily or twice daily? Vascul Pharmacol. 2013 Sep-Oct;59 (3-4):53–62.
  16. Eriksson BI, Dahl OE, Buller HR, Hettiarachchi R, Rosencher N, Bravo ML et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005 Jan;3 (1):103–11.
  17. Buxton I. The dynamics of drug absorption, distribution, action, and elimination. Goodman & Gilman's The pharmacological basis of therapeutics, 11 ed. – McGraw Hill, 2006. – P 1–39. (издание имеет ISBN)
  18. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141 (2 Suppl): e419S-94S.
  19. Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59–7939, an oral, direct Factor Xa inhibitor. Clin Pharmacol Ther. 2005 Oct;78 (4):412–21.
  20. Eriksson BI, Dahl OE, Ahnfelt L, Kalebo P, Stangier J, Nehmiz G et al. Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost. 2004 Sep;2 (9):1573–80.
  21. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikeboom JW et al. 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. J Am Coll Cardiol. 2014 Feb 4;63 (4):321–8.
  22. Cohen D. Dabigatran: how the drug company withheld important analyses. BMJ. 2014 Jul 23;349: g4670.
  23. Mueck W, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK et al. Population pharmacokinetics and pharmacodynamics of once and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Haemost. 2008 Sep;100 (3):453–61.
  24. Buller HR, Lensing AW, Prins MH, Agnelli G, Cohen A, Gallus AS et al. A dose-ranging study evaluating once-daily oral administration of the Factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT dose-ranging study. Blood. 2008 Sep 15;112 (6):2242–7.
  25. Mueck W, Lensing AW, Agnelli G, Decousus H, Prandoni P, Misselwitz F. Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet. 2011 Oct;50 (10):675–86.
  26. Agnelli G, Gallus A, Goldhaber SZ, Haas S, Huisman MV, Hull RD et al. Treatment of proximal deep-vein thrombosis with the oral direct Factor Xa inhibitor rivaroxaban (BAY 59–7939): the ODIXa-DVT (oral direct Factor Xa inhibitor BAY 59–7939 in patients with acute symptomatic deep-vein thrombosis) study. Circulation. 2007 Jul 10;116 (2):180–7.
  27. Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D. The efficacy and safety of apixaban, an oral, direct Factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost. 2007 Dec;5 (12):2368–75.
  28. Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD et al. Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010 Mar;159 (3):331–9.
  29. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363 (26): 2487–98.
  30. Weitz JI, Connolly SJ, Patel I, Salazar D, Rohatagi S, Mendell J et al. 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 Sep;104 (3):633–41.
  31. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012 focused update of the ESC guidelines for the mana­gement of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012 Nov;33 (21):2719–47.
  32. Gong IY, Kim RB. Importance of pharmacokinetic profile and variability as determinants of dose and response to dabigatran, rivaroxa­ban, and apixaban. Can J Cardiol. 2013 Jul;29 (7 Suppl): S24–33.
  33. Savelieva I, Camm AJ. Practical considerations for using novel oral anticoagulants in patients with atrial fibrillation. Clin Cardiol. 2014 Jan;37 (1):32–47.
  34. Kneeland PP, Fang MC. Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism. Patient Prefer Adherence. 2010 Mar 24;4:51–60.
  35. Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Ouellette VL. How often is medication taken as prescribed? A novel assessment technique. JAMA. 1989 Jun 9;261 (22):3273–7.
  36. Coleman CI, Roberts MS, Sobieraj DM, Lee S, Alam T, Kaur R. Effect of dosing frequency on chronic cardiovascular disease medication adherence. Curr Med Res Opin. 2012 May;28 (5):669–80.
  37. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001 Aug;23 (8):1296–310.
  38. Laliberte F, NelsonWW, Lefebvre P, Schein JR, Rondeau-Leclaire J, Duh MS. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther. 2012 Aug;29 (8):675–90.
  39. Beyer-Westendorf J, Förster K, Pannach S, Ebertz F, Gelbricht V, Thieme C, Michalski F, Köhler C, Werth S, Sahin K, Tittl L, Hänsel U, Weiss N. Rates, management, and outcome of rivaroxaban blee­ding in daily care: results from the Dresden NOAC registry. Blood. 2014 Aug 7;124 (6):955–62.
  40. Beyer-Westendorf J, Ebertz F, Förster K, Gelbricht V, Michalski F, Kohler C et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost. 2015 Jun;113 (6):1247–57.
  41. Nelson WW, Song X, Coleman CI, Thomson E, Smith DM, Damaraju CV, Schein JR. Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation. Curr Med Res Opin. 2014 Dec;30 (12):2461–9.
  42. Beyer-Westendorf J, Förster K, Ebertz F, Gelbricht V, Schreier T, Gobelt M et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace. 2015 Apr;17 (4):530–8.
Сычев Д. А., Крюков А. В., Савельева М. И., Рябова А. В., Цомая И. В. Клинико-фармакологические аспекты применения новых оральных антикоагулянтов у пациентов с фибрилляцией предсердий. Сердце: журнал для практикующих врачей. 2015;14 (6):402–410

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