rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2012-8-6-819-825rpcardio-643Research ArticlePOINT OF VIEWТОЧКА ЗРЕНИЯHOW TO USE DABIGATRAN IN PATIENTS WITH ATRIAL FIBRILLATIONКОГДА И КАК ПРИМЕНЯТЬ ДАБИГАТРАН ПРИ ФИБРИЛЛЯЦИИ ПРЕДСЕРДИЙМоисеевС. В.MoiseevS. V.

д.м.н., профессор кафедры терапии и профболезней медико-профилактического факультета Первого МГМУ им. И. М. Сеченова; профессор кафедры внутренних болезней МГУ им. М.В. Ломоносова

clinpharm@mtu-net.ruПервый Московский медицинский университет им. И.М. Сеченова Московский государственный университет им. М.В. ЛомоносоваРоссияI.M. Sechenov First Moscow State Medial University Lomonosov Moscow State UniversityRussian Federation20120901201686819825Copyright © Moiseev S.V., 20152015Моисеев С.В.Moiseev S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/643

Dabigatran is the new oral anticoagulant that directly inhibits thrombin (factor IIa). In RE-LY clinical trial dabigatran 150 mg b.i.d was more effective than warfarin in prevention of ischemic stroke and systemic embolic events in more than 18000 patients with nonvalvular atrial fibrillation. At that time dabigatran and warfarin showed similar safety. Practical issues of dabigatran treatment, e.g. therapeutic indications, choice of dosage etc. are discussed.

Дабигатрана этексилат (в тексте также именуемый как дабигатран) — это новый пероральный антикоагулянт , оказывающий прямое ингибирующее действие на тромбин (фактор IIa). В исследовании RE-LY более чем у 18000 пациентов с неклапанной фибрилляцией предсердий (ФП) дабигатран в дозе 150 мг два раза в сутки превосходил варфарин по эффективности в профилактике инсульта и системных тромбоэмболий и не уступал ему по безопасности. Обсуждаются практические аспекты применения дабигатрана при ФП, в том числе показания к назначению, выбор дозы и т.д.

фибрилляция предсердийишемический инсультпрофилактикадабигатранatrial fibrillationischemic strokepreventiondabigatranReferencesHart R., Pearce L., Aguilar M. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857–67.Hart R., Pearce L., Aguilar M. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857–67.Mant J., Hobbs F., Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493–503.Mant J., Hobbs F., Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493–503.Connolly S. Pogue J., Hart R. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903–12.Connolly S. Pogue J., Hart R. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903–12.Connolly S., Ezekowitz M., Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–1151.Connolly S., Ezekowitz M., Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–1151.Roskell N., Lip G., Noack H. et al. Treatments for stroke prevention in atrial fibrillation: A network meta-analyses and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2011; 102: Thromb Haemost 2010;104(6):1106–15..Roskell N., Lip G., Noack H. et al. Treatments for stroke prevention in atrial fibrillation: A network meta-analyses and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2011; 102: Thromb Haemost 2010;104(6):1106–15..Hart R., Pearce L., Rothbart R. et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000; 35 (1): 183–7.Hart R., Pearce L., Rothbart R. et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000; 35 (1): 183–7.Hohnloser S., Pajitnev D., Pogue J. et al. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol 2007; 50 (22): 2156–61.Hohnloser S., Pajitnev D., Pogue J. et al. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol 2007; 50 (22): 2156–61.Flaker G., Ezekowitz M., Yusuf S. et al. Efficacy and safety of dabigatran compared to warfarin in patients with paroxysmal, persistent, and permanent atrial fibrillation: results from the RE-LY (Random-ized Evaluation of Long-Term Anticoagulation Therapy) study. J Am Coll Cardiol 2012; 59 (9): 854– 855.Flaker G., Ezekowitz M., Yusuf S. et al. Efficacy and safety of dabigatran compared to warfarin in patients with paroxysmal, persistent, and permanent atrial fibrillation: results from the RE-LY (Random-ized Evaluation of Long-Term Anticoagulation Therapy) study. J Am Coll Cardiol 2012; 59 (9): 854– 855.The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Guidelines for the management of atrial fibrillation. Eur Heart J 2010; 31: 2369–2429.The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Guidelines for the management of atrial fibrillation. Eur Heart J 2010; 31: 2369–2429.National guidelines for the diagnosis and treatment of atrial fibrillation. M.: VNOK; 2011. Russian (На-циональные рекомендации по диагностике и лечению фибрилляции предсердий. М.: ВНОК; 2011).National guidelines for the diagnosis and treatment of atrial fibrillation. M.: VNOK; 2011. Russian (На-циональные рекомендации по диагностике и лечению фибрилляции предсердий. М.: ВНОК; 2011).Yavelov I.S., Moiseev S.V. Antithrombotic therapy in current recommendations for the treatment of atrial fibrillation. Klinichekaya Farmakologiya i Terapiya 2011; 20 (3): 64–70. Russian (Явелов И.С., Моисеев С.В. Антитромботическая терапия в современных рекомендациях по лечению фибрилляции предсердий. Клиничекая Фармакология и Терапия 2011; 20 (3): 64–70).Yavelov I.S., Moiseev S.V. Antithrombotic therapy in current recommendations for the treatment of atrial fibrillation. Klinichekaya Farmakologiya i Terapiya 2011; 20 (3): 64–70. Russian (Явелов И.С., Моисеев С.В. Антитромботическая терапия в современных рекомендациях по лечению фибрилляции предсердий. Клиничекая Фармакология и Терапия 2011; 20 (3): 64–70).Pisters R., Lane D., Nieuwhat R. et al. A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest 2010;138(5):1093–100.Pisters R., Lane D., Nieuwhat R. et al. A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest 2010;138(5):1093–100.Diener H.S., Connly S., Ezekowitz M. et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol 2010; 9: 1157–63.Diener H.S., Connly S., Ezekowitz M. et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol 2010; 9: 1157–63.Huisman M., Lip G., Diener H.S. et al. Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice Thromb Haemost 2012; 107: 838–47.Huisman M., Lip G., Diener H.S. et al. Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice Thromb Haemost 2012; 107: 838–47.Oldgren J., Alings M., Darius H. et al. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med 2011; 155 (10): 660–667.Oldgren J., Alings M., Darius H. et al. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med 2011; 155 (10): 660–667.Ferreira J., Ezekowitz M., Connolly S. et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. 84th Sci Sess 2011 of the American Heart Association (AHA), Orlando, 12–16 Nov 2011. Circulation 2011; 124 (21 Suppl): Abstract 10956.Ferreira J., Ezekowitz M., Connolly S. et al. Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. 84th Sci Sess 2011 of the American Heart Association (AHA), Orlando, 12–16 Nov 2011. Circulation 2011; 124 (21 Suppl): Abstract 10956.Van de Werf F, Brueckmann M, Connolly SJ A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am Heart J 2012;163(6):931–937.Van de Werf F, Brueckmann M, Connolly SJ A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am Heart J 2012;163(6):931–937.Eikelboom J., Wallentin L., Connolly S. et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011; 123 (21): 2363–72.Eikelboom J., Wallentin L., Connolly S. et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011; 123 (21): 2363–72.Healey J., Eikelboom J., Wallentin L. et al. Effect of age and renal function on the risks of stroke and major bleeding with dabigatran compared to warfarin: an analysis from the RE-LY study. ACC.10, 59th Ann Sci Sess of the American College of Cardiology, Atlanta, 14–16 Mar 2010 (Poster).Healey J., Eikelboom J., Wallentin L. et al. Effect of age and renal function on the risks of stroke and major bleeding with dabigatran compared to warfarin: an analysis from the RE-LY study. ACC.10, 59th Ann Sci Sess of the American College of Cardiology, Atlanta, 14–16 Mar 2010 (Poster).van Ryn J., Stangier J., Haertter S. et al. Dabigatran etexilate — a novel, reversible, oral direct throm-bin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 11116–27.van Ryn J., Stangier J., Haertter S. et al. Dabigatran etexilate — a novel, reversible, oral direct throm-bin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 11116–27.Nagarakanti R., Ezekowitz M., Oldgren J. et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 2011; 123: 131–36.Nagarakanti R., Ezekowitz M., Oldgren J. et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 2011; 123: 131–36.Dans A., Connolly S., Bruckmann M. et al. RE-LY: concomitant use of antiplatelet therapy with dabigatran or warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. 33rd Cong of the European Society of Cardiology (ESC), Paris, 27–31 Aug 2011.Dans A., Connolly S., Bruckmann M. et al. RE-LY: concomitant use of antiplatelet therapy with dabigatran or warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. 33rd Cong of the European Society of Cardiology (ESC), Paris, 27–31 Aug 2011.Ezekowitz M., Wallentin L., Connolly S. et al. Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation. Circulation 2010; 122 (22): 2246–53.Ezekowitz M., Wallentin L., Connolly S. et al. Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation. Circulation 2010; 122 (22): 2246–53.Hohnloser S., Oldgren J., Yang S. et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 2012; 125 (5): 669–76.Hohnloser S., Oldgren J., Yang S. et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 2012; 125 (5): 669–76.Reilly P., Conrad C., Faaij R. et al. Concomitant use of P-glycoprotein inhibitors with dabigatran or war-farin in the RE-LY trial (abstract 129). Eur Heart J 2011; 32 (Suppl. 1): 6.Reilly P., Conrad C., Faaij R. et al. Concomitant use of P-glycoprotein inhibitors with dabigatran or war-farin in the RE-LY trial (abstract 129). Eur Heart J 2011; 32 (Suppl. 1): 6.

The authors declare that there are no conflicts of interest present.