10 лет исследованию ARISTOTLE: итоги и уроки

Остроумова О.Д., Буторов В.Н., Миронова Е.В., Долдо Н.М. 10 лет исследованию ARISTOTLE: итоги и уроки. Consilium Medicum. 2021; 23 (6): 477–484. DOI: 10.26442/20751753.2021.6.200991

________________________________________________

Ostroumova OD, Butorov VN, Mironova EV, Doldo NM. 10 years of ARISTOTLE trial: results and lessons. Consilium Medicum. 2021; 23 (6): 477–484. DOI: 10.26442/20751753.2021.6.200991

Читать PDF

Аннотация

В 2021 г. мировое кардиологическое сообщество отмечает юбилей одного из величайших исследований в клинической медицине – исследования Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). В исследовании показано, что у пациентов с фибрилляцией предсердий применение апиксабана было более эффективным, чем применение варфарина в профилактике инсульта или системной эмболии, сопровождалось меньшей частотой кровотечений и было сопряжено с более низкой смертностью от всех причин. К настоящему времени опубликовано 77 субанализов этого грандиозного исследования, краткий обзор которых приведен в статье. Как показал post-hoc анализ исследования ARISTOTLE, апиксабан одинаково эффективен и безопасен как у пациентов без сопутствующей патологии, так и у полиморбидных больных. Эффективность и безопасность апиксабана были продемонстрированы при фибрилляции предсердий и наличии сопутствующих заболеваний, в том числе сахарного диабета, хронической болезни почек, ожирения, ишемической болезни сердца. Ряд субанализов исследования ARISTOTLE посвящен прогностической оценке таких биомаркеров, как сердечные тропонины, фактор дифференциации роста-15, N-концевой натрийуретический пептид про-В-типа, D-димер, асимметричный и симметричный диметиларгинин, интерлейкин-6, С-реактивный белок. На основании исследования биомаркеров были созданы новые, более информативные шкалы оценки риска развития инсульта, летального исхода и кровотечений: шкала АВС-инсульт, шкала АВС-летальный исход и шкала АВС-кровотечения. Данные соответствующих субанализов подтвердили большую эффективность и/или безопасность лечения апиксабаном по сравнению с варфарином независимо от уровня различных биомаркеров в плазме крови и степени риска развития инсульта, летального исхода и кровотечений, оцениваемых как с помощью традиционных, так и новых шкал.

Ключевые слова: исследование ARISTOTLE, апиксабан, фибрилляция предсердий, сопутствующие заболевания, полиморбидность, биомаркеры, ABC-шкала

________________________________________________

In 2021, the world cardiology community celebrates the anniversary of one of the greatest research in clinical medicine – the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study. The study showed that in patients with atrial fibrillation, the use of apixaban was more effective than the use of warfarin in the prevention of stroke or systemic embolism, was accompanied by a lower frequency of bleeding and was associated with lower mortality from all causes. To date, 77 subanalyses of this ambitious study have been published, a brief overview of which is given in the article. As shown by the post-hoc analysis of the ARISTOTLE study, apixaban was equally effective and safe both in patients without comorbidities and in polymorbid patients. The efficacy and safety of apixaban has been demonstrated in atrial fibrillation and in the presence of comorbidities, including diabetes mellitus, chronic kidney disease, obesity, and coronary heart disease. A number of subanalyses of the ARISTOTLE study are devoted to the prognostic assessment of biomarkers such as cardiac troponins, growth differentiation factor-15,
pro-B-type N-terminal natriuretic peptide, D-dimer, asymmetric and symmetric dimethylarginine, interleukin-6, C-reactive protein. Based on the study of biomarkers, new, more informative scales for assessing the risk of stroke, death and bleeding were created: the ABC-stroke scale, the ABC-lethal outcome scale and the ABC-bleeding scale. The data of the corresponding sub-analyzes confirmed the greater efficacy and/or safety of apixaban treatment compared with warfarin, regardless of the level of various biomarkers in blood plasma and the degree of risk of stroke, death and bleeding, assessed using both traditional and new scales.

Keywords: ARISTOTLE trial, apixaban, atrial fibrillation, concomitant diseases, multimorbidity, biomarkers, ABC scale

Полный текст

Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.

Список литературы

1. Granger CB, Alexander JH, McMurray JJV, et al. for the ARISTOTLE committees and investigators. ARISTOTLE primary results. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-92. DOI:10.1056/NEJMoa1107039
2. Drazen’s Dozen: articles that changed practice since 2000. N Engl J Med. Available at: https://cdn.nejm.org/pdf/Drazens-Dozen.pdf. Accessed: 15.06.21.
3. Lopes RD, Alexander JH, Al-Khatib SM, et al.; ARISTOTLE Investigators. Apixaban for Reduction In Stroke and other ThromboemboLic Events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010;159(3):331-9. DOI:10.1016/j.ahj.2009.07.035
4. Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in nonsurgical patients. J Thromb Haemost. 2005;3(4):692-4. DOI:10.1111/j.1538-7836.2005.01204.x
5. Ottervanger JP, Armstrong P, Barnathan ES, et al.; GUSTO IV-ACS Investigators. Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV--Acute Coronary Syndrome) Trial Global Use of Strategies To Open Occluded Coronary Arteries IV-Acute Coronary Syndrome – GUSTO IV-ACS One Year Follow-up. Circulation. 2003;107(3):437-42. DOI:10.1161/01.cir.0000046487.06811.5e
6. Rao AK, Pratt C, Berke A, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial – phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol. 1988;11(1):1-11. DOI:10.1016/0735-1097(88)90158-1
7. Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and tromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 2011;342:d124. DOI:10.1136/bmj.d124
8. DuGoff EH, Canudas-Romo V, Buttorff C, et al. Multiple chronic conditions and life expectancy: a life table analysis. Med Care. 2014;52(8):688-94.
DOI:10.1097/MLR.0000000000000166
9. Brambatti M, Darius H, Oldgren J, et al. Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial. Int J Cardiol. 2015;196:127-31. DOI:10.1016/j.ijcard.2015.05.141
10. De Caterina R, Patti G, Westerbergh J, et al. Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation: an analysis of the ARISTOTLE trial. Eur Heart J Cardiovasc Pharmacother. 2020;pvaa140. DOI:10.1093/ehjcvp/pvaa140
11. Ezekowitz JA, Lewis BS, Renato LD, et al. Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban: results from the ARISTOTLE trial. Eur Heart J Cardiovasc Pharmacother. 2015;1:86-94. DOI:10.1093/ehjcvp/pvu024
12. Benjamin EJ, Blaha MJ, Chiuve SE, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics – 2017 Update: A Report From the American Heart Association. Circulation. 2017;135:e146-e603. DOI:10.1161/CIR.0000000000000485
13. Hohnloser SH, Hijazi Z, Thomas L, et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2012;33(22):2821-30. DOI:10.1093/eurheartj/ehs274
14. Hijazi Z, Hohnloser SH, Andersson U, et al. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2016;1(4):451-60. DOI:10.1001/jamacardio.2016.1170
15. Stanifer JW, Pokorney SD, Chertow GM, et al. Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease. Circulation. 2020;28;141(17):1384-92. DOI:10.1161/CIRCULATIONAHA.119.044059
16. Hijazi Z, Granger CB, Hohnloser SH, et al. Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation. J Am Heart Assoc. 2020;9:e017155. DOI:10.1161/JAHA.120.017155
17. Sandhu RK, Ezekowitz J, Andersson U, et al. The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Eur Heart J. 2016;37(38):2869-78. DOI:10.1093/eurheartj/ehw124
18. Hohnloser SH, Fudim M, Alexander JH, et al. Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight Insights From the ARISTOTLE Tria. Circulation. 2019;139:2292-300.
DOI:10.1161/CIRCULATIONAHA.118.037955
19. Batra G, Svennblad B, Held C, et al. All types of atrial fibrillation in the setting of myocardial infarction are associated with impaired outcome. Heart. 2016;102(12):926-33. DOI:10.1136/heartjnl-2015-308678
20. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806-17. DOI:10.1056/NEJMoa1007432
21. Bahit MC, Lopes RD, Wojdyla DM, et al. Apixaban in patients with atrial fibrillation and prior coronary artery disease: insights from the ARISTOTLE trial. Int J Cardiol. 2013;170(2):215-20. DOI:10.1016/j.ijcard.2013.10.062
22. Lopes RD, Al-Khatib SM, Wallentin L, et al. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012;380(9855):1749-58. DOI:10.1016/S0140-6736(12)60986-6
23. Wallentin L, Lopes RD, Hanna M, et al.; ARISTOTLE Investigators. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation. 2013;127:2166-76. DOI:10.1161/CIRCULATIONAHA.114.011204
24. Sharma A, Hijazi Z, Andersson U, et al. The use of biomarkers to predict specific causes of death in patients with atrial fibrillation: Insights from the ARISTOTLE trial. Circulation. 2018;138(16):1666-76. DOI:10.1161/CIRCULATIONAHA.118.034125
25. Hijazi Z, Wallentin L, Siegbahn A, et al. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation). J Am Coll Cardiol. 2013;61:2274-84. DOI:10.1016/j.jacc.2012.11.082
26. Christersson C, Wallentin L, Andersson U, et al. D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation – observations from the ARISTOTLE trial. J Thromb Haemost. 2014;12(9):1401-12. DOI:10.1111/jth.12638
27. Horowitz JD, De Caterina R, Heresztyn T, et al.; ARISTOTLE Investigators. Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy. J Am Coll Cardiol. 2018;72(7):721-33. DOI:10.1016/j.jacc.2018.05.058
28. Aulin J, Hijazi Z, Siegbahn A, et al. Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials. J Thromb Haemost. 2020;18:2287-95. DOI:10.1111/jth.14947
29. Hijazi Z, Aulin J, Andersson U et al.; ARISTOTLE Investigators. Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. Heart. 2016;102:508-17. DOI:10.1136/heartjnl-2015-308887
30. Hijazi Z, Lindbäck J, Alexander JH et al.; ARISTOTLE and STABILITY Investigators. The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J. 2016;37(20):1582-90. DOI:10.1093/eurheartj/ehw054
31. Hijazi Z, Wallentin L, Siegbahn A, et al.; ARISTOTLE Investigators. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. J Am Coll Cardiol. 2014;63:52-61. DOI:10.1016/j.jacc.2013.07.093
32. Hijazi Z, Siegbahn A, Andersson U, et al.; ARISTOTLE Investigators. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thrombolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2014;129:625-34. DOI:10.1161/CIRCULATIONAHA.113.006286
33. Røsjø H, Hijazi Z, Omland T, et al. Cardiac troponin is associated with cardiac outcomes in men and women with atrial fibrillation, insights from the ARISTOTLE trial. J Intern Med. 2020;288(2):248-59. DOI:10.1111/joim.13072
34. Oldgren J, Hijazi Z, Lindbäck J, et al.; RE-LY and ARISTOTLE Investigators. Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation. Circulation. 2016;134(22):1697-707. DOI:10.1161/CIRCULATIONAHA.116.022802
35. Hijazi Z, Oldgren J, Lindbäck J, et al.; ARISTOTLE and RE-LY Investigators. A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. Eur Heart J. 2018;39(6):477-85. DOI:10.1093/eurheartj/ehx584
36. Hijazi Z, Oldgren J, Lindbäck J, et al.; ARISTOTLE and RЕ-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 2016;387(10035):2302-11. DOI:10.1016/S0140-6736(16)00741-8
37. Hijazi Z, Oldgren J, Lindbäck J, et al. Evaluation of the Age, Biomarkers, and Clinical History-Bleeding Risk Score in Patients With Atrial Fibrillation With Combined Aspirin and Anticoagulation. Therapy Enrolled in the ARISTOTLE and RE-LY Trials. JAMA Network Open. 2020;3(9):e2015943. DOI:10.1001/jamanetworkopen.2020.15943
38. Vinereanu D, Lopes RD, Mulder H, et al.; ARISTOTLE Investigators. Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin. Stroke. 2017;48(12):3266-73. DOI:10.1161/STROKEAHA.117.017574

________________________________________________

Авторы

О.Д. Остроумова*1, В.Н. Буторов1, Е.В. Миронова2, Н.М. Долдо2

1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
2 ЧУЗ «Центральная клиническая больница “РЖД-Медицина”», Москва, Россия
*ostroumova.olga@mail.ru

________________________________________________

Olga D. Ostroumova*1, Vasiliy N. Butorov1, Elena V. Mironova2, Nikolai M. Doldo2

1 Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
2 Central Clinical Hospital “Russian Railways-Medicine”, Moscow, Russia
*ostroumova.olga@mail.ru

Назад к списку

Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.

10 лет исследованию ARISTOTLE: итоги и уроки

10 лет исследованию ARISTOTLE: итоги и уроки

Ключевые слова