medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-5-20-25medsovet-2347Research ArticleИШЕМИЧЕСКАЯ БОЛЕЗНЬ СЕРДЦАISHEMIC HEART DISEASEНовые оральные антикоагулянты и коронарная безопасность: есть ли проблема?New oral anticoagulants and cardiac safety: do we have a problem?НифонтовЕ. М.NifontovE. M.

д.м.н., профессор

MD, Prof.

Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov First Saint Petersburg State Medical UniversityRussian Federation201810042018052025Copyright © Нифонтов Е.М., 20182018Нифонтов Е.М.Nifontov E.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2347

В аналитическом обзоре представлены сведения о частоте развития инфаркта миокарда при использовании прямых оральных антикоагулянтов в рандомизированных клинических исследованиях и двух наблюдательных когортных исследованиях FDA, опубликованных в 2012 и 2017 гг. Отмечена большая частота инфарктов при применении прямого ингибитора тромбина дабигатрана по сравнению с варфарином. Блокатор Хa-фактора ривароксабан имеет наиболее убедительные доказательства коронарной безопасности.

 

This analytic review provides the information about frequency of myocardial infarction in patients, treated with direct oral anticoagulants in randomized clinical trials and retrospective cohort studies. It is indicated that direct thrombin inhibitor dabigatran has higher incidence of myocardial infarctions than warfarin. Direct factor Xa inhibitor rivaroxaban has the most convincing arguments of coronary safety.

 

апиксабандабигатранривароксабанинфаркт миокардаapixabandabigatranrivaroxabanmyocardial infarctionReferencesKirchhof P, Benussi Si, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal, doi: 10.1093/ eurheartj/e.Kirchhof P, Benussi Si, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal, doi: 10.1093/ eurheartj/e.Konstantinides SV, Torbicki A, Agnelli G. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) Endorsed by the European Respiratory Society (ERS). Eur. Heart J., 2014, 35: 3033-3080.Konstantinides SV, Torbicki A, Agnelli G. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) Endorsed by the European Respiratory Society (ERS). Eur. Heart J., 2014, 35: 3033-3080.The EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, et al. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med, 2010, 363: 2499-510.The EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, et al. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med, 2010, 363: 2499-510.Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N. Engl. J. Med., 2009, 361(24): 2342– 2352.Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N. Engl. J. Med., 2009, 361(24): 2342– 2352.Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thomp-son J, Raskob GE, Weitz JI. Oral Apixaban for the Treatment of Acute Venous Thrombo embo lism. N. Engl. J. Med., 2013, 369(9): 799–808.Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thomp-son J, Raskob GE, Weitz JI. Oral Apixaban for the Treatment of Acute Venous Thrombo embo lism. N. Engl. J. Med., 2013, 369(9): 799–808.Turpie AGG, Lassen MR, Eriksson BI, et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost, 2011, 105: 444-453.Turpie AGG, Lassen MR, Eriksson BI, et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost, 2011, 105: 444-453.Schulman S, Kakkar AK, Goldhaber SZ, Schel-long S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation, 2014, 129(7): 764–772.Schulman S, Kakkar AK, Goldhaber SZ, Schel-long S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation, 2014, 129(7): 764–772.Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet, 2010, 375: 807-815.Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet, 2010, 375: 807-815.Gibson CM, Mehran R, Bode C et al. Prevention of Bleeding in Patients with Atrial Fibrillation Under going PCI. N Engl J Med, 2016, 375: 2423-34.Gibson CM, Mehran R, Bode C et al. Prevention of Bleeding in Patients with Atrial Fibrillation Under going PCI. N Engl J Med, 2016, 375: 2423-34.Cannon CP et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial fibrillation. N Engl J Med, 2017. doi: 10.1056/NEJMoa1708454.Cannon CP et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial fibrillation. N Engl J Med, 2017. doi: 10.1056/NEJMoa1708454.Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med, 2012, 366(1): 9-19.Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med, 2012, 366(1): 9-19.Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med, 2017, 377: 1319-30.Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med, 2017, 377: 1319-30.Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabiga tran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med, 2009, 361: 1139-51.Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabiga tran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med, 2009, 361: 1139-51.Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, et al. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med, 2011, 365: 883-91.Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, et al. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med, 2011, 365: 883-91.Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M еt al. Apixaban versus Warfarin in Patients withAtrial Fibrillation. New England Journal of Medicine, 2011, 365(11): 981–92.Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M еt al. Apixaban versus Warfarin in Patients withAtrial Fibrillation. New England Journal of Medicine, 2011, 365(11): 981–92.Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med, 2009, 361: 1139-51.Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med, 2009, 361: 1139-51.Patel MR, Mahaffey KW, Garg J et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 2011, 365(10): 883–891. doi: 10.1056/NEJMoa1009638.Patel MR, Mahaffey KW, Garg J et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 2011, 365(10): 883–891. doi: 10.1056/NEJMoa1009638.Mak KH. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials. BMJ Open, 2012, 2: e001592.Mak KH. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials. BMJ Open, 2012, 2: e001592.Loke YK, Pradhan S, Yeong JK, Kwok CS. Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison. Br J Clin Pharmacol, 2014 Oct, 78(4): 707-17.Loke YK, Pradhan S, Yeong JK, Kwok CS. Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison. Br J Clin Pharmacol, 2014 Oct, 78(4): 707-17.Tornyos A, Kehl D, D’Ascenzo F, Komócsi A et al. Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment. Prog Cardiovasc Dis, 2016 Mar-Apr, 58(5): 483-94.Tornyos A, Kehl D, D’Ascenzo F, Komócsi A et al. Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment. Prog Cardiovasc Dis, 2016 Mar-Apr, 58(5): 483-94.Sipahi I., Celik S., Akyol A. Dabigatran's 'real-world' data about risk of myocardial infarction and gastrointestinal bleeding contradicts with randomized trials. JACC, 2013 September 3, Vol. 62, No. 10, 2013: 945–6.Sipahi I., Celik S., Akyol A. Dabigatran's 'real-world' data about risk of myocardial infarction and gastrointestinal bleeding contradicts with randomized trials. JACC, 2013 September 3, Vol. 62, No. 10, 2013: 945–6.FDA Drug Safety Communication: FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin. http: // www.fda.gov/drugs/drugsafety/ucm396470.htm.FDA Drug Safety Communication: FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin. http: // www.fda.gov/drugs/drugsafety/ucm396470.htm.Azoulay L еt al. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes. Eur Heart J, 2014 July, 35(Issue 28): 1881–1887. doi.org/10.1093/eurheartj/eht499.Azoulay L еt al. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes. Eur Heart J, 2014 July, 35(Issue 28): 1881–1887. doi.org/10.1093/eurheartj/eht499.Nazarian RM et al. Warfarin-induced skin necrosis. Am Acad Dermatol, 2009, 61: 325–332.Nazarian RM et al. Warfarin-induced skin necrosis. Am Acad Dermatol, 2009, 61: 325–332.Mega JL, Braunwald E, Wiviott SD et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome. N Engl J Med, 2012, 366(1): 9–19.Mega JL, Braunwald E, Wiviott SD et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome. N Engl J Med, 2012, 366(1): 9–19.Eikelboom JW, Connolly SJ, Bosch J et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med, 2017, AugEikelboom JW, Connolly SJ, Bosch J et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med, 2017, Augdoi: 10.1056 / NEJMoa1709118.doi: 10.1056 / NEJMoa1709118.Gibson CM, Mehran R, Bode C et al, Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med, 2016, 375:2423-2434Gibson CM, Mehran R, Bode C et al, Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med, 2016, 375:2423-2434Cannon CP, Bhatt DL, Oldgren J et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med, 2017, 377:1513-1524.Cannon CP, Bhatt DL, Oldgren J et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med, 2017, 377:1513-1524.Alan S. Go AS et al. Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice. Ann Intern Med, 2017, 167: 845-854. doi: 10.7326/M16-1157.Alan S. Go AS et al. Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice. Ann Intern Med, 2017, 167: 845-854. doi: 10.7326/M16-1157.Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei Bet al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg, 2016 Nov, 50(5): e1-e88.Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei Bet al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg, 2016 Nov, 50(5): e1-e88.Laliberté F et al. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther, 2012, 29(8): 675–690.Laliberté F et al. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther, 2012, 29(8): 675–690.Skeppholm M, Kallner A, Malmqvist K, Blomback M, Wallen H. Is fibrin formation and thrombin generation increased during and after an acute coronary syndrome? Thromb Res, 2011, 128(5): 483-489.Skeppholm M, Kallner A, Malmqvist K, Blomback M, Wallen H. Is fibrin formation and thrombin generation increased during and after an acute coronary syndrome? Thromb Res, 2011, 128(5): 483-489.

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