rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2018-14-2-272-283rpcardio-1659Research ArticlePOINT OF VIEWТОЧКА ЗРЕНИЯNew Possibilities of Antithrombotic Therapy of Patients with Peripheral and Widespread Atherosclerotic LesionНОВЫЕ ВОЗМОЖНОСТИ АНТИТРОМБОТИЧЕСКОЙ ТЕРАПИИ БОЛЬНЫХ С ПЕРИФЕРИЧЕСКИМ И РАСПРОСТРАНЕННЫМ АТЕРОСКЛЕРОТИЧЕСКИМ ПОРАЖЕНИЕМКомаровА. Л.KomarovA. L.

Комаров Андрей Леонидович – доктор медицинских наук, ведущий научный сотрудник, отдел клинических проблем атеротромбоза

121552, Москва, ул. 3-я Черепковская, 15а

Andrei L. Komarov – MD, PhD, Leading Researcher, Department of Clinical Problems of Atherothrombosis

Tretya Cherepkovskaya ul. 15a, Moscow, 121552

andrkomarov@mail.ruНовиковаЕ. C.NovikovaЕ. S.

Новикова Елена Степановна – аспирант, отдел клинических проблем атеротромбоза

121552, Москва, ул. 3-я Черепковская, 15а

Elena S. Novikova – MD, Postgraduate Student, Department of Clinical Problems of Atherothrombosis

Tretya Cherepkovskaya ul. 15a, Moscow, 121552

ГуськоваЕ. В.GuskovaE. V.

Гуськова Екатерина Владимировна – кандидат медицинских наук, врач-кардиолог

105203, Москва, ул. Нижняя Первомайская, 70

Ekaterina V. Guskova – MD, PhD, Cardiologist

Nizhnyaya Pervomayskaya ul. 70, Moscow, 105203

ЯроваяЕ. Б.YarovayaЕ. B.

Яровая Елена Борисовна – доктор физико-математических наук, профессор, кафедра теории вероятностей, механико-математический факультет

119991, Москва, Ленинские горы, 1 

 

Elena B. Yarovaya – PhD (Mathematics and Physics), Professor, Chair of Probability Theory, Faculty of Mechanics and Mathematics

Leninskie Gory 1, Moscow, 119991

СамкоА. Н.SamkoA. N.

Самко Анатолий Николаевич – доктор медицинских наук, профессор, руководитель отдела рентгенэндоваскулярных методов диагностики и лечения

121552, Москва, ул. 3-я Черепковская, 15а

Anatoly N. Samko – MD, PhD, Professor, Head of Department of X-ray Endovascular Methods of Diagnosis and Treatment

Tretya Cherepkovskaya ul. 15a, Moscow, 121552

ПанченкоЕ. П.PanchenkoE. Р.

Панченко Елизавета Павловна – доктор медицинских наук, профессор, руководитель отдела клинических проблем атеротромбоза

121552, Москва, ул. 3-я Черепковская, 15а

Elizaveta P. Panchenko – MD, PhD, Professor, Head of Department of Clinical Problems of Atherothrombosis

Tretya Cherepkovskaya ul. 15a, Moscow, 121552

Национальный медицинский исследовательский центр кардиологииРоссияNational Medical Research Center of CardiologyRussian FederationНациональный медико-хирургический центр им. Н.И. ПироговаРоссияNational Pirogov Medical Surgical CenterRussian FederationМосковский Государственный Университет им. М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian Federation201801052018142272283Copyright © Komarov A.L., Novikova Е.S., Guskova E.V., Yarovaya Е.B., Samko A.N., Panchenko E.Р., 20182018Комаров А.Л., Новикова Е.C., Гуськова Е.В., Яровая Е.Б., Самко А.Н., Панченко Е.П.Komarov A.L., Novikova Е.S., Guskova E.V., Yarovaya Е.B., Samko A.N., Panchenko E.Р.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/1659

Atherosclerotic peripheral artery disease (PAD) is well-known thrombotic risk factor in different cohorts of patients. This current review analyzes epidemiological data of trials and registries about influence both clinical and asymptomatic peripheral atherosclerotic disease on adverse ischemic events. Individual assessment of the atherothrombotic prevalence, which is directly related to vascular thrombotic risk, remains an important problem. Issue of PAD routine screening using traditional methods of ultrasound duplex scanning, measurement of ankle-brachial index is discussed in details. Comparative efficiency of present antiplatelet and anticoagulant drugs is shown in the key of preventing PAD thrombotic complications. PAD detection can be the reason for "intensification" of antithrombotic treatment, the only one option of which until recently was an additional treatment with P2Y12 platelet receptors blockers. However, the routine treatment with dual antiplatelet therapy in stable manifestations of atherothrombosis is not supported by the current guidelines. In this regard, it seems relevant to intensify therapy by simultaneously affecting on the platelet and plasma components of hemostasis in patients with PAD, that was demonstrated in a recently published study COMPASS. Treatment with rivaroxaban small doses in addition to acetylsalicylic acid allowed to improve significantly outcomes in a wide range of patients with stable manifestations of atherothrombosis without high risk of bleeding and severe renal impairment. However, use of this multicomponent therapy has not been approved by relevant clinical recommendations yet, which causes certain difficulties in choosing optimal scheme of antithrombotic treatment among patients with PAD.

Атеросклеротическое заболевание периферических артерий (ЗПА) является признанным фактором риска тромботических осложнений у различных категорий больных. В настоящей работе представлены эпидемиологические данные исследований и регистров о влиянии как симптомного, так и бессимптомного атеросклеротического поражения периферических сосудистых бассейнов на развитие неблагоприятных ишемических исходов. Индивидуальная оценка степени распространенности атеротромбоза, напрямую связанной с риском сосудистых катастроф, остается важной проблемой. Подробно обсуждается целесообразность рутинного скрининга на предмет ЗПА с использованием традиционных методов ультразвукового дуплексного сканирования, измерения лодыжечно-плечевого индекса. Приведены данные исследований о сравнительной эффективности современных антиагрегантных и антикоагулянтных препаратов в профилактике тромботических событий у больных с атеротромбозом. Обнаружение ЗПА может быть основанием для «интенсификации» атитромботического лечения, единственным вариантом которого до недавнего времени являлось дополнительное назначение блокаторов P2Y12 рецепторов тромбоцитов. Однако рутинное назначение двойной антиагрегантной терапии при стабильных проявлениях атеротромбоза не поддерживается современными рекомендациями. В этой связи у больных с ЗПА представляется актуальным усиление терапии за счет одновременного воздействия на тромбоцитарное и плазменное звенья гемостаза, что было продемонстрировано в недавно опубликованном исследовании COMPASS. Назначение малых доз ривароксабана дополнительно к ацетилсалициловой кислоте позволило существенно улучшить исходы у широкого круга больных со стабильными проявлениями атеротромбоза различной локализации, не имеющих высокого риска кровотечений и выраженных нарушений функции почек. Однако применение данной многокомпонентной терапии пока еще не одобрено соответствующими клиническими рекомендациями, что создает определенные трудности при выборе оптимальной схемы антитромботического лечения среди пациентов с ЗПА.

Атеросклеротическое заболевание периферических артерийтромботические осложненияантитромботическое лечениедвойная антитромбоцитарная терапияАtherosclerotic peripheral artery diseasethrombotic eventsantithrombotic treatmentdual antiplatelet therapyReferencesJuergens J.L., Barker N.W., Hines E.A. Arteriosclerosis obliterans: review of 520 cases with special reference to pathogenic and prognostic factors. Circulation. 1960;21:188-95.Juergens J.L., Barker N.W., Hines E.A. Arteriosclerosis obliterans: review of 520 cases with special reference to pathogenic and prognostic factors. Circulation. 1960;21:188-95.Dormandy J., Mahir M., Ascady G., et al. Fate of the patient with chronic leg ischaemia. A review article. J Cardiovasc Surg (Torino). 1989;30:50-7.Dormandy J., Mahir M., Ascady G., et al. Fate of the patient with chronic leg ischaemia. A review article. J Cardiovasc Surg (Torino). 1989;30:50-7.Smith G.D., Shipley M.J., Rose G. Intermittent claudication, heart disease risk factors, and mortality: The Whitehall Study. Circulation. 1990;82(6):1925-31. doi: 10.1161/01.CIR.82.6.1925.Smith G.D., Shipley M.J., Rose G. Intermittent claudication, heart disease risk factors, and mortality: The Whitehall Study. Circulation. 1990;82(6):1925-31. doi: 10.1161/01.CIR.82.6.1925.Criqui M.N., Langer R.D., Fronek A., et al. Mortality over a period of 10 years in patients with peripheral arterial occlusive disease. N Engl J Med. 1992;326:381-6. doi: 10.1056/NEJM199202063260605.Criqui M.N., Langer R.D., Fronek A., et al. Mortality over a period of 10 years in patients with peripheral arterial occlusive disease. N Engl J Med. 1992;326:381-6. doi: 10.1056/NEJM199202063260605.Wilterdink J.L., Easton J.D. Vascular event rates in patients with atherosclerotic cerebrovascular disease. Arch Neurol. 1992;49:857-63.Wilterdink J.L., Easton J.D. Vascular event rates in patients with atherosclerotic cerebrovascular disease. Arch Neurol. 1992;49:857-63.Halliday A., Bax J.J. The 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in Collaboration With the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018 Mar;55(3):301-302. doi: 10.1016/j.ejvs.2018.03.004.Halliday A., Bax J.J. The 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in Collaboration With the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018 Mar;55(3):301-302. doi: 10.1016/j.ejvs.2018.03.004.CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348(9038):1329-39. doi: 10.1016/S01406736(96)09457-3.CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348(9038):1329-39. doi: 10.1016/S01406736(96)09457-3.Комаров А.Л., Панченко Е.П. Частота поражений различных сосудистых бассейнов и медикаментозное лечение больных с высоким риском атеротромботических осложнений. Российские результаты международного исследования AGATHA. Кардиология. 2004;44(11):39-44.Komarov A.L., Panchenko E.P. The damage frequency of different vascular beds and medical treatment of patients with high atherothrombotic risk. Russian results of the international research AGATHA. Kardiologiia. 2004;44(11):39-44. (In Russ.)Bhatt D.L., Steg P.G., Ohman E.M. et al. REACH Registry Investigators. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295(2):180-9. doi: 10.1001/jama.295.2.180.Bhatt D.L., Steg P.G., Ohman E.M. et al. REACH Registry Investigators. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295(2):180-9. doi: 10.1001/jama.295.2.180.Панченко Е.П. Результаты трехлетнего наблюдения за амбулаторными больными с клиническими проявлениями атеротромбоза (анализ российской популяции регистра REACH). Кардиология. 2009;10:9-15.Panchenko E.P. Results of three year observation of outpatients with clinical manifestations of atherothrombosis (analysis of russian population of REACH registry) Kardiologiia. 2009;10:9-15. (In Russ.)Alberts M.J., Bhatt D.L., Mas J.L. et al. REduction of Atherothrombosis for Continued Health Registry Investigators. Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry. Eur Heart J. 2009;30(19):2318-26. doi: 10.1093/eurheartj/ehp355.Alberts M.J., Bhatt D.L., Mas J.L. et al. REduction of Atherothrombosis for Continued Health Registry Investigators. Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry. Eur Heart J. 2009;30(19):2318-26. doi: 10.1093/eurheartj/ehp355.Kernan W.N., Ovbiagele B., Black H.R. et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-236. doi: 10.1161/STR.0000000000000024.Kernan W.N., Ovbiagele B., Black H.R. et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-236. doi: 10.1161/STR.0000000000000024.2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315-381. doi: 10.1093/eurheartj/ehw106.2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315-381. doi: 10.1093/eurheartj/ehw106.2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease. Journal of the American College of Cardiology 2017;69(11):71-126 doi: 10.1016/j.jacc.2016.11.007.2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease. Journal of the American College of Cardiology 2017;69(11):71-126 doi: 10.1016/j.jacc.2016.11.007.Заболевания артерий нижних конечностей. Клинические рекомендации (2016). Доступно на: https://racvs.ru/clinic/files/2016/Diseases-lower-limb-arteries.pdf. Проверено 17.04.2018.Lower extremity peripheral artery disease. Clinical guidelines (2016). Available at: https://racvs.ru/clinic/files/2016/Diseases-lower-limb-arteries.pdf. Checked by Apr 17, 2018. (In Russ.)Hirsch A.T., Criqui M.H., Treat-Jacobson D. et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286(11):1317-24. doi:10.1001/jama.286.11.1317.Hirsch A.T., Criqui M.H., Treat-Jacobson D. et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286(11):1317-24. doi:10.1001/jama.286.11.1317.Resnick H.E., Lindsay R.S., McDermott M.M. et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation 2004;109(6):733-9. doi: 10.1161/01.CIR.0000112642.63927.54.Resnick H.E., Lindsay R.S., McDermott M.M. et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation 2004;109(6):733-9. doi: 10.1161/01.CIR.0000112642.63927.54.Komarov A.L., Panchenko E.P., Dobrovolsky A.B. et al. D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease. Eur Heart J. 2002;23(16):1309-16.Komarov A.L., Panchenko E.P., Dobrovolsky A.B. et al. D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease. Eur Heart J. 2002;23(16):1309-16.Комаров А.Л. Д-димер и функция тромбоцитов как предикторы тромботических осложнений у больных с атеросклеротическим поражением артерий нижних конечностей (результаты 5-летнего наблюдения). Кардиология. 2000;9:16-22.Komarov A.L. D-dimer and function of platelets as predictors of thrombotic events in patients with peripheral arterial disease of the lower extremities (results of 5 years' observation). Kardiologiia. 2000;9:16-22. (In Russ.)Hiatt W.R., Fowkes F.G., Heizer G. et al. EUCLID Trial Steering Committee and Investigators. Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. N Engl J Med 2017;376(1):32-40. doi: 10.1056/NEJMoa1611688.Hiatt W.R., Fowkes F.G., Heizer G. et al. EUCLID Trial Steering Committee and Investigators. Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. N Engl J Med 2017;376(1):32-40. doi: 10.1056/NEJMoa1611688.Johnston S.C., Amarenco P., Albers G.W. et al. SOCRATES Steering Committee and Investigators. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med 2016;375(1):35-43. doi: 10.1056/NEJMoa1603060.Johnston S.C., Amarenco P., Albers G.W. et al. SOCRATES Steering Committee and Investigators. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med 2016;375(1):35-43. doi: 10.1056/NEJMoa1603060.Bhatt D.L., Fox K.A., Hacke W. et al. CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706-17. doi: 10.1056/NEJMoa060989.Bhatt D.L., Fox K.A., Hacke W. et al. CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706-17. doi: 10.1056/NEJMoa060989.Bhatt D.L., Flather M.D., Hacke W. et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49:1982-8. doi: 10.1016/j.jacc.2007.03.025.Bhatt D.L., Flather M.D., Hacke W. et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49:1982-8. doi: 10.1016/j.jacc.2007.03.025.Franzone A., Piccolo R., Gargiulo G. et al. Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease: A Subgroup Analysis of the PRODIGY Randomized Clinical Trial. JAMA Cardiol. 2016;1(7):795-803. doi:0.1001/jamacardio.2016.2811.Franzone A., Piccolo R., Gargiulo G. et al. Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease: A Subgroup Analysis of the PRODIGY Randomized Clinical Trial. JAMA Cardiol. 2016;1(7):795-803. doi:0.1001/jamacardio.2016.2811.Bonaca M.P., Bhatt D.L., Storey R.F. et al. Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. J Am Coll Cardiol 2016;67(23):2719-2728. doi:10.1016/j.jacc.2016.03.524.Bonaca M.P., Bhatt D.L., Storey R.F. et al. Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. J Am Coll Cardiol 2016;67(23):2719-2728. doi:10.1016/j.jacc.2016.03.524.2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. European Heart Journal 2017;0:1-48 doi:10.1093/eurheartj/ehx419.2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. European Heart Journal 2017;0:1-48 doi:10.1093/eurheartj/ehx419.Bonaca M.P., Scirica B.M., Creager M.A. et al. Vorapaxar in patients with peripheral artery disease: results from TRAP-TIMI 50. Circulation. 2013;127(14):1522-9. doi: 10.1161/CIRCULATIONAHA.112.000679.Bonaca M.P., Scirica B.M., Creager M.A. et al. Vorapaxar in patients with peripheral artery disease: results from TRAP-TIMI 50. Circulation. 2013;127(14):1522-9. doi: 10.1161/CIRCULATIONAHA.112.000679.Panchenko E., Dobrovolsky A., Davletov K. et al. D-dimer and fibrinolysis in patients with various degrees of atherosclerosis. Eur Heart J. 1995;16(1):38-42.Panchenko E., Dobrovolsky A., Davletov K. et al. D-dimer and fibrinolysis in patients with various degrees of atherosclerosis. Eur Heart J. 1995;16(1):38-42.Hurlen M., Abdelnoor M., Smith P. et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347:969-74. doi: 10.1056/NEJMoa020496.Hurlen M., Abdelnoor M., Smith P. et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347:969-74. doi: 10.1056/NEJMoa020496.Andreotti F., Testa L., Biondi-Zoccai G.G., Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: An updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J. 2006;27:519-26. doi: 10.1093/eurheartj/ehi485.Andreotti F., Testa L., Biondi-Zoccai G.G., Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: An updated and comprehensive meta-analysis of 25;307 patients. Eur Heart J. 2006,27:519-26. doi: 10.1093/eurheartj/ehi485.Mega J.L., Braunwald E., Wiviott S.D. et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome. N Engl J Med. 2012;366:9-19. doi: 10.1056/NEJMoa1112277.Mega J.L., Braunwald E., Wiviott S.D. et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome. N Engl J Med. 2012;366:9-19. doi: 10.1056/NEJMoa1112277.2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2016;37: 67-315. doi:10.1093/eurheartj/ehv320.2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2016;37: 67-315. doi:10.1093/eurheartj/ehv320.2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2017;0:1-66. doi:10.1093/eurheartj/ehx393.2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2017,0:1-66. doi:10.1093/eurheartj/ehx393.2014 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal doi:10.1093/eurheartj/ehu278.2014 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal doi:10.1093/eurheartj/ehu278.Руда М. Я., Аверков О. В., Панченко Е. П., Явелов И. С. Клинические рекомендации по диагностике и лечению больных c острым коронарным синдромом без подъема сегмента ST электрокардиограммы. Кардиология. 2017;57(8):80-100.Ruda M.Y., Averkov O.V., Panchenko E.P., Yavelov I.S. Clinical guidelines on the diagnosis and treatment of patients with nonSTsegment elevation acute coronary syndrome. Kardiologiia. 2017;57(8):80-100. (In Russ.)Bosch J., Eikelboom J.W., Connolly S.J. et al. Rationale, Design and Baseline Characteristics of Participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) Trial. Can J Cardiol. 2017;33(8):1027-1035. doi: 10.1016/j.cjca.2017.06.001.Bosch J., Eikelboom J.W., Connolly S.J. et al. Rationale, Design and Baseline Characteristics of Participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) Trial. Can J Cardiol. 2017;33(8):1027-1035. doi: 10.1016/j.cjca.2017.06.001.Eikelboom J.W., Connolly S.J., Bosch J. et al., on behalf of the COMPASS investigators. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377(14):1319-30. doi: 10.1056/NEJMoa1709118.Eikelboom J.W., Connolly S.J., Bosch J. et al., on behalf of the COMPASS investigators. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377(14):1319-30. doi: 10.1056/NEJMoa1709118.Connolly S.J., Eikelboom J.W., Bosch J. et al on behalf of the COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391:205-18. doi: 10.1016/S01406736(17)32458-3.Connolly S.J., Eikelboom J.W., Bosch J. et al on behalf of the COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391:205-18. doi: 10.1016/S01406736(17)32458-3.Anand S.S., Bosch J., Eikelboom J.W. et al on behalf of the COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 Nov 10. pii: S01406736(17)32409-1. doi: 10.1016/S0140-6736(17)32409-1.Anand S.S., Bosch J., Eikelboom J.W. et al on behalf of the COMPASS investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 Nov 10. pii: S01406736(17)32409-1. doi: 10.1016/S0140-6736(17)32409-1.Darmon A., Bhatt D.L., Elbez Y. et al. External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registry. Eur Heart J.;39(9):750-7. doi: 10.1093/eurheartj/ehx658.Darmon A., Bhatt D.L., Elbez Y. et al. External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registry. Eur Heart J.;39(9):750-7. doi: 10.1093/eurheartj/ehx658.Safety of Long-Term PPI Use. JAMA. 2017;318(12):1177-8. doi:10.1001/jama.2017.13272.Safety of Long-Term PPI Use. JAMA. 2017;318(12):1177-8. doi:10.1001/jama.2017.13272.

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