Статья
Комбинированная антитромботическая терапия у больных со стабильным течением сердечно-сосудистых заболеваний, обусловленных атеросклерозом: какое направление показал COMPASS?
Современная вторичная профилактика у пациентов со стабильной ишемической болезнью сердца (ИБС) и/или заболеванием периферических артерий (ЗПА), включающая антитромбоцитарную монотерапию, ассоциируется со значительным остаточным риском развития повторных сердечно-сосудистых осложнений (ССО). Внедрение в практику результатов многих современных исследований по оценке эффективности вторичной профилактики атеротромбоза затруднительно. Дополнительное воздействие на коагуляцию крови способно играть ключевую роль в предупреждении атеротромбоза. В исследовании COMPASS у пациентов с ИБС и/или ЗПА добавление ривароксабана в дозе 2,5 мг 2 раза в день к ацетилсалициловой кислоте (АСК), по сравнению с АСК в виде монотерапии, значительно снижало риск смерти от сердечно-сосудистых осложнений, развития инфаркта миокарда или инсульта и смерти по любой причине. При комбинированной антитромботической терапии увеличивался риск больших, но не фатальных, или внутричерепных кровотечений. У больных с ЗПА дополнительно снижался риск тяжелых ишемических осложнений в области нижних конечностей, включая ампутации. По данным анализа в подгруппах исследования COMPASS, добавление ривароксабана в дозе 2,5 мг 2 раза в день к АСК может оказаться наиболее полезным для пациентов со стабильным атеросклеротическим заболеванием при высоком риске тяжелых ССО и без высокого риска кровотечений.
1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP et al. Heart Disease and Stroke Statistics – 2019 Update: A Report From the American Heart Association. Circulation. 2019;139(10):e56–528. DOI: 10.1161/CIR.0000000000000659
2. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE et al. 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):e71–126. DOI: 10.1016/j.jacc.2016.11.007
3. Bhatt DL, Eagle KA, Ohman EM, Hirsch AT, Goto S, Mahoney EM et al. Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis. JAMA. 2010;304(12):1350–7. DOI: 10.1001/jama.2010.1322
4. Steg PhG, Bhatt DL, Wilson PWF, D’Agostino R, Ohman EM, Röther J et al. One-Year Cardiovascular Event Rates in Outpatients With Atherothrombosis. JAMA. 2007;297(11):1197. DOI: 10.1001/jama.297.11.1197
5. Maron DJ, Mancini GBJ, Hartigan PM, Spertus JA, Sedlis SP, Kostuk WJ et al. Healthy Behavior, Risk Factor Control, and Survival in the COURAGE Trial. Journal of the American College of Cardiology. 2018;72(19):2297–305. DOI: 10.1016/j.jacc.2018.08.2163
6. Kotseva K, Wood D, De Bacquer D. Determinants of participation and risk factor control according to attendance in cardiac rehabilitation programmes in coronary patients in Europe: EUROASPIRE IV survey. European Journal of Preventive Cardiology. 2018;25(12):1242– 51. DOI: 10.1177/2047487318781359
7. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082–143.. DOI: 10.1161/CIR.0000000000000625
8. De Backer G, Jankowski P, Kotseva K, Mirrakhimov E, Reiner Ž, Rydén L et al. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis. 2019;285:135–46. DOI: 10.1016/j.atherosclerosis.2019.03.014
9. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. New England Journal of Medicine. 2015;372(25):2387– 97. DOI: 10.1056/NEJMoa1410489
10. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine. 2017;376(18):1713–22. DOI: 10.1056/NEJMoa1615664
11. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine. 2018;379(22):2097–107. DOI: 10.1056/NEJMoa1801174
12. Kazi DS, Penko J, Coxson PG, Guzman D, Wei PC, Bibbins-Domingo K. Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Annals of Internal Medicine. 2019;170(4):221–9. DOI: 10.7326/M18-1776
13. Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management. Journal of the American College of Cardiology. 2018;72(3):330–43. DOI: 10.1016/j.jacc.2018.04.061
14. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England Journal of Medicine. 2019;380(1):11–22. DOI: 10.1056/NEJMoa1812792
15. Diamantis E, Kyriakos G, Quiles-Sanchez LV, Farmaki P, Troupis T. The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature. Current Cardiology Reviews. 2017;13(3):209–16. DOI: 10.2174/1573403X13666170426104611
16. Ridker PM. Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin. European Heart Journal. 2016;37(22):1720–2. DOI: 10.1093/eurheartj/ehw024
17. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine. 2017;377(12):1119–31. DOI: 10.1056/NEJMoa1707914
18. Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. New England Journal of Medicine. 2019;380(8):752–62. DOI: 10.1056/NEJMoa1809798
19. Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L et al. Interpretation of the evidence for the efficacy and safety of statin therapy. The Lancet. 2016;388(10059):2532–61. DOI: 10.1016/S0140-6736(16)31357-5
20. Libby P. Mechanisms of Acute Coronary Syndromes. New England Journal of Medicine. 2013;369(9):882–4. DOI: 10.1056/NEJMc1307806
21. Angiolillo DJ, Ueno M, Goto S. Basic Principles of Platelet Biology and Clinical Implications. Circulation Journal. 2010;74(4):597–607. DOI: 10.1253/circj.CJ-09-0982
22. Montalescot G, Sechtem W, Achenbach S, Andreotti F, Arden C, Budaj A et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronaryartery disease of the European Society of Cardiology. European Heart Journal. 2013;34(38):2949–3003. DOI: 10.1093/eurheartj/eht296
23. Aboyans V, Ricco J-B, Bartelink M-LEL, Björck M, Brodmann M, Cohnert T et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). European Heart Journal. 2018;39(9):763–816. DOI: 10.1093/eurheartj/ehx095
24. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. The Lancet. 2009;373(9678):1849–60. DOI: 10.1016/S0140-6736(09)60503-1
25. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet (London, England). 1996;348(9038):1329–39. PMID: 8918275
26. Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj A et al. Oral Anticoagulant and Antiplatelet Therapy and Peripheral Arterial Disease. New England Journal of Medicine. 2007;357(3):217–27. DOI: 10.1056/NEJMoa065959
27. Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. New England Journal of Medicine. 2016;375(1):35–43. DOI: 10.1056/NEJMoa1603060
28. Schunkert H, Boening A, von Scheidt M, Lanig C, Gusmini F, de Waha A et al. Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial. European Heart Journal. 2019;40(29):2432–40. DOI: 10.1093/eurheartj/ehz185
29. Hiatt WR, Fowkes FGR, Heizer G, Berger JS, Baumgartner I, Held P et al. Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. New England Journal of Medicine. 2017;376(1):32–40. DOI: 10.1056/NEJMoa1611688
30. Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR. Warfarin plus Aspirin after Myocardial Infarction or the Acute Coronary Syndrome: Meta-Analysis with Estimates of Risk and Benefit. Annals of Internal Medicine. 2005;143(4):241–50. DOI: 10.7326/0003-4819-143-4-200508160-00005
31. Bhatt DL, Fox KAA, Hacke W, Berger PB, Black HR, Boden WE et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. The New England Journal of Medicine. 2006;354(16):1706–17. DOI: 10.1056/NEJMoa060989
32. Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC et al. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. New England Journal of Medicine. 2015;372(19):1791–800. DOI: 10.1056/NEJMoa1500857
33. Bonaca MP, Bhatt DL, Storey RF, Steg PhG, Cohen M, Kuder J et al. Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. Journal of the American College of Cardiology. 2016;67(23):2719–28. DOI: 10.1016/j.jacc.2016.03.524
34. Moon JY, Franchi F, Rollini F, Angiolillo DJ. The quest for safer antithrombotic treatment regimens in patients with coronary artery disease: new strategies and paradigm shifts. Expert Review of Hematology. 2018;11(1):5–12. DOI: 10.1080/17474086.2018.1400378
35. Angiolillo DJ, Capodanno D, Goto S. Platelet thrombin receptor antagonism and atherothrombosis. European Heart Journal. 2010;31(1):17–28. DOI: 10.1093/eurheartj/ehp504
36. Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP et al. Vorapaxar in the Secondary Prevention of Atherothrombotic Events. New England Journal of Medicine. 2012;366(15):1404–13. DOI: 10.1056/NEJMoa1200933
37. Bonaca MP, Creager MA, Olin J, Scirica BM, Gilchrist IC, Murphy SA et al. Peripheral Revascularization in Patients With Peripheral Artery Disease With Vorapaxar: Insights From the TRA 2°P-TIMI 50 Trial. JACC: Cardiovascular Interventions. 2016;9(20):2157–64. DOI: 10.1016/j.jcin.2016.07.034
38. Moon JY, Nagaraju D, Franchi F, Rollini F, Angiolillo DJ. The role of oral anticoagulant therapy in patients with acute coronary syndrome. Therapeutic Advances in Hematology. 2017;8(12):353–66. DOI: 10.1177/2040620717733691
39. Mega JL, Braunwald E, Wiviott SD, Bassand J-P, Bhatt DL, Bode C et al. Rivaroxaban in patients with a recent acute coronary syndrome. The New England Journal of Medicine. 2012;366(1):9–19. DOI: 10.1056/NEJMoa1112277
40. Sanmartín M, Bellmunt S, Cosín-Sales J, García-Moll X, Riera-Mestre A, Almendro-Delia M et al. Role of rivaroxaban in the prevention of atherosclerotic events. Expert Review of Clinical Pharmacology. 2019;12(8):771–80. DOI: 10.1080/17512433.2019.1637732
41. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. New England Journal of Medicine. 2017;377(14):1319–30. DOI: 10.1056/NEJMoa1709118
42. Bosch J, Eikelboom JW, Connolly SJ, Bruns NC, Lanius V, Yuan F et al. Rationale, Design and Baseline Characteristics of Participants in the C ardiovascular O utco m es for P eople Using A nticoagulation S trategie s (COMPASS) Trial. Canadian Journal of Cardiology. 2017;33(8):1027–35. DOI: 10.1016/j.cjca.2017.06.001
43. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients: Definitions of major bleeding in clinical studies. Journal of Thrombosis and Haemostasis. 2005;3(4):692–4. DOI: 10.1111/j.1538-7836.2005.01204.x
44. Sharma M, Hart RG, Connolly SJ, Bosch J, Shestakovska O, Ng KKH et al. Stroke Outcomes in the COMPASS Trial. Circulation. 2019;139(9):1134– 45. DOI: 10.1161/CIRCULATIONAHA.118.035864
45. Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. The Lancet. 2018;391(10117):205–18. DOI: 10.1016/S0140-6736(17)32458-3
46. Панченко Е.П. по поручению участников регистра REACH в РФ. Результаты трехлетнего наблюдения за амбулаторными больными с клиническими проявлениями атеротромбоза (анализ российской популяции регистра REACH). Кардиология. 2009;49(10):9–15
47. Kownator S, Cambou J-P, Cacoub P, Léger P, Luizy F, Herrmann M-A et al. Prevalence of unknown peripheral arterial disease in patients with coronary artery disease: Data in primary care from the IPSILON study. Archives of Cardiovascular Diseases. 2009;102(8–9):625–31. DOI: 10.1016/j.acvd.2009.05.004
48. Anand SS, Bosch J, Eikelboom JW, Connolly SJ, Diaz R, Widimsky P et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. The Lancet. 2018;391(10117):219–29. DOI: 10.1016/S0140-6736(17)32409-1
49. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL et al. International Prevalence, Recognition, and Treatment of Cardiovascular Risk Factors in Outpatients With Atherothrombosis. JAMA. 2006;295(2):180. DOI: 10.1001/jama.295.2.180
50. Bittner V, Bertolet M, Barraza Felix R, Farkouh ME, Goldberg S, Ramanathan KB et al. Comprehensive Cardiovascular Risk Factor Control Improves Survival. Journal of the American College of Cardiology. 2015;66(7):765–73. DOI: 10.1016/j.jacc.2015.06.019
51. Hingorani A, LaMuraglia GM, Henke P, Meissner MH, Loretz L, Zinszer KM et al. The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. Journal of Vascular Surgery. 2016;63(2 Suppl):3S-21S. DOI: 10.1016/j.jvs.2015.10.003
52. Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, GoldsteinFuchs J et al. Diabetic Kidney Disease: A Report From an ADA Consensus Conference. Diabetes Care. 2014;37(10):2864–83. DOI: 10.2337/dc14-1296
53. Low Wang CC, Blomster JI, Heizer G, Berger JS, Baumgartner I, Fowkes FGR et al. Cardiovascular and Limb Outcomes in Patients With Diabetes and Peripheral Artery Disease. Journal of the American College of Cardiology. 2018;72(25):3274–84. DOI: 10.1016/j.jacc.2018.09.078
54. American Diabetes Association. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes – 2019. Diabetes Care. 2019;42(Suppl 1):S103–23. DOI: 10.2337/dc19-S010
55. Dumaine RL, Montalescot G, Steg PhG, Ohman EM, Eagle K, Bhatt DL. Renal function, atherothrombosis extent, and outcomes in high-risk patients. American Heart Journal. 2009;158(1):141-148. e1. DOI: 10.1016/j.ahj.2009.05.011
56. Hakeem A, Bhatti S, Karmali KN, Dillie KS, Cook JR, Xu J et al. Renal Function and Risk Stratification of Diabetic and Nondiabetic Patients Undergoing Evaluation for Coronary Artery Disease. JACC: Cardiovascular Imaging. 2010;3(7):734–45. DOI: 10.1016/j.jcmg.2010.06.001
57. Fox KAA, Eikelboom JW, Shestakovska O, Connolly SJ, Metsarinne KP, Yusuf S. Rivaroxaban Plus Aspirin in Patients With Vascular Disease and Renal Dysfunction: From the COMPASS Trial. Journal of the American College of Cardiology. 2019;73(18):2243–50. DOI: 10.1016/j.jacc.2019.02.048
58. Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. European Heart Journal. 2015;36(19):1163–70. DOI: 10.1093/eurheartj/ehu505
59. Nakatani D, Sakata Y, Suna S, Usami M, Matsumoto S, Shimizu et al. Incidence, Predictors, and Subsequent Mortality Risk of Recurrent Myocardial Infarction in Patients Following Discharge for Acute Myocardial Infarction. Circulation Journal. 2013;77(2):439–46. DOI: 10.1253/circj.CJ-11-1059
60. Шальнова С.А., Оганов Р.Г., Стэг Ф.Г., Форд Й. Ишемическая болезнь сердца. Современная реальность по данным всемирного регистра CLARIFY. Кардиология. 2013;53(8):28-33
61. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O et al. Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, DoubleBlind, Placebo-Controlled Trial. Gastroenterology. 2019;157(2):403412.e5. DOI: 10.1053/j.gastro.2019.04.041
62. Eikelboom JW, Connolly SJ, Bosch J, Shestakovska O, Aboyans V, Alings M et al. Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis. Circulation. 2019;140(18):1451–9. DOI: 10.1161/CIRCULATIONAHA.119.041949
63. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/AHA Versus ESC Guidelines on Dual Antiplatelet Therapy. Journal of the American College of Cardiology. 2018;72(23):2915– 31. DOI: 10.1016/j.jacc.2018.09.057
64. Elliott J, Kelly SE, Bai Z, Liu W, Skidmore B, Boucher M et al. Optimal Duration of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention: An Umbrella Review. Canadian Journal of Cardiology. 2019;35(8):1039–46. DOI: 10.1016/j.cjca.2019.01.021
65. Yin S-H-L, Xu P, Wang B, Lu Y, Wu Q-Y, Zhou M-L et al. Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis. BMJ. 2019;365:l2222. DOI: 10.1136/bmj.l2222
66. Sumaya W, Geisler T, Kristensen SD, Storey RF. Dual antiplatelet or Dual Antithrombotic Therapy for Secondary Prevention in HighRisk Patients with Stable Coronary Artery Disease? Thrombosis and Haemostasis. 2019;19(10):1583–9. DOI: 10.1055/s-0039-1679903
67. Hiatt WR, Hess CN, Bonaca MP. Heterogeneity of Risk and Benefit in Subgroups of COMPASS: Relatively Similar But Absolutely Different. Journal of the American College of Cardiology. 2019;73(25):3292–4. DOI: 10.1016/j.jacc.2019.05.007
68. Anand SS, Eikelboom JW, Dyal L, Bosch J, Neumann C, Widimsky P et al. Rivaroxaban Plus Aspirin Versus Aspirin in Relation to Vascular Risk in the COMPASS Trial. Journal of the American College of Cardiology. 2019;73(25):3271–80. DOI: 10.1016/j.jacc.2019.02.079
69. Darmon A, Bhatt DL, Elbez Y, Aboyans V, Anand S, Bosch J et al. External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registry. European Heart Journal. 2018;39(9):750–757a. DOI: 10.1093/eurheartj/ehx658