Современная стратегия в лечении артериальной гипертонии: комбинированная терапия и фиксированные комбинации
Современная стратегия в лечении артериальной гипертонии: комбинированная терапия и фиксированные комбинации
Леонова М.В. Современная стратегия в лечении артериальной гипертонии: комбинированная терапия и фиксированные комбинации. Consilium Medicum. 2021; 23 (6): 485–490.
DOI: 10.26442/20751753.2021.6.200942
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Leonova MV. Modern strategy in the treatment of arterial hypertension: combination therapy and fixed combinations. Consilium Medicum. 2021; 23 (6): 485–490. DOI: 10.26442/20751753.2021.6.200942
Современная стратегия в лечении артериальной гипертонии: комбинированная терапия и фиксированные комбинации
Леонова М.В. Современная стратегия в лечении артериальной гипертонии: комбинированная терапия и фиксированные комбинации. Consilium Medicum. 2021; 23 (6): 485–490.
DOI: 10.26442/20751753.2021.6.200942
________________________________________________
Leonova MV. Modern strategy in the treatment of arterial hypertension: combination therapy and fixed combinations. Consilium Medicum. 2021; 23 (6): 485–490. DOI: 10.26442/20751753.2021.6.200942
Внедрение фиксированных комбинаций для лечения артериальной гипертонии (АГ) – это эффективная стратегия, направленная на решение проблемы бремени сердечно-сосудистых заболеваний для общественного здравоохранения. Эта стратегия нашла отражение в современных международных руководствах по лечению АГ и поддержана Всемирной организацией здравоохранения. Применение фиксированной комбинации позволяет решать ключевые практические задачи для достижения лучших результатов и улучшения прогноза АГ: обеспечение наибольшей степени снижения артериального давления (АД) и его более низкого целевого уровня, сокращение временного периода для получения целевого АД, повышение приверженности лечению. Фиксированные комбинации включают классы антигипертензивных препаратов, которые при сочетании обладают аддитивным или синергическим действием в снижении АД, способствуют уменьшению/смягчению побочных эффектов, уменьшают количество таблеток и повышают приверженность пациентов, решая проблему полипрагмазии. Однократное дозирование фиксированных комбинаций является еще одним важным преимуществом, обеспечивая приверженность, большую продолжительность действия и уменьшение суточных колебаний АД. Клинические преимущества фиксированных комбинаций подтверждены в ряде крупных исследований и метаанализов. Современная тактика применения фиксированных комбинаций предусматривает их использование на разных стадиях/степени повышения АД. В этой связи разработаны фиксированные комбинации с субтерапевтическими, терапевтическими и максимальными дозами компонентных препаратов. Для использования фиксированных комбинаций в качестве начальной терапии АГ предлагаются препараты с субтерапевтическими дозами компонентов, которые не используются при монотерапии. В таких случаях благодаря комплементарному подбору сочетаемых препаратов можно добиться более значительного и своевременного снижения АД с меньшим количеством побочных эффектов. Современные фиксированные комбинации основаны на 3 основных классах антигипертензивных препаратов: блокаторы ренин-ангиотензин-альдостероновой системы – РААС (ингибиторы ангиотензинпревращающего фермента и блокаторы рецепторов ангиотензина II), антагонисты кальция и диуретики. Выделяется 2 принципиальных подхода комбинаций: сочетание блокаторов РААС с диуретиками (диуретиксодержащие) или сочетание блокаторов РААС с антагонистами кальция (не диуретиксодержащие). Такое предпочтение обусловлено результатами доказательной медицины, включая вопросы эффективности, переносимости, побочных эффектов, и подтвержденными исследованиями. В клинических рекомендациях по лечению АГ эти комбинации относятся к предпочтительным (уровень доказательности А). Со временем все больше фиксированных комбинаций становятся непатентованными и появляются надежные генерические комбинированные препараты для лечения АГ, что позволяет снизить стоимость и делает терапию экономически приемлемой.
The introduction of fixed combinations for the treatment of arterial hypertension (AH) is an effective strategy to address the public health burden of cardiovascular disease. This strategy is reflected in modern international guidelines for the treatment of AH and is supported by World Health Organization. The use of fixed combinations allows solving key practical problems to achieve better results and improve the prognosis of AH: ensuring the greatest decrease in blood pressure (BP) and a lower target BP level, shortening the time period for obtaining target BP, increasing adherence to treatment. Fixed combinations include classes of antihypertensive drugs, which, when combined, have an additive or synergistic effect in lowering BP, help to reduce/mitigate side effects, reduce the number of pills and increase patient adherence, solving the problem of polypharmacy. Single dosing per day of fixed combinations is another important benefit, providing adherence, longer duration of action, and reduced diurnal fluctuations in BP. The clinical benefits of fixed combinations have been confirmed in a number of large studies and meta-analyzes. The modern tactics of using fixed combinations provides for their use at different stages/degrees of BP increase. In this regard, fixed combinations with subtherapeutic, therapeutic and maximum therapeutic doses of components have been developed. For the use of fixed combinations as an initial therapy for AH, drugs with subtherapeutic doses of components that are not used in monotherapy are proposed. In such cases, thanks to the complementary selection of combined drugs, it is possible to achieve a more significant and timely BP reduction, with fewer side effects. Modern fixed combinations are based on three main classes of antihypertensive drugs – RAAS blockers (ACE inhibitors and ARBs), calcium antagonists and diuretics. There are 2 principal approaches to combinations: a combination of RAAS blockers with diuretics (diurethic-use) or a combination of RAAS blockers with calcium antagonists (diuretic-free). This preference is due to evidence-based medicine data, including questions of efficacy, tolerability, side effects, and confirmation in clinical trials. In the clinical guidelines for the treatment of hypertension, these combinations are considered preferred (evidence level A). Over time, more and more fixed combinations become generic and reliable generic combination drugs for the treatment of hypertension appear, which reduces the cost factor and makes the therapy economically acceptable.
Keywords: arterial hypertension, fixed combinations, antihypertensive drugs, blockers of the renin-angiotensin-aldosterone system, thiazides, adherence
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26. Salam A, Kanukul R, Atkins E, et al. Efficacy and safety of dual combination therapy of blood pressure-lowering drugs as initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(9):1768-74. DOI:10.1097/HJH.0000000000002096
27. Tung YC, Huang YC, Wu LS, et al. Medication compliance and clinical outcomes of fixed-dose combinations vs free combinations of an angiotensin II receptor blocker and a calcium channel blocker in hypertension treatment. J Clin Hypertens (Greenwich). 2017;19(10):983-9. DOI:10.1111/jch.13035
28. Ho CT, Tung YC, Chou SH et al. Clinical outcomes in hypertensive patients treated with a single-pill fixed-dose combination of renin-angiotensin system inhibitor and thiazide diuretic. J Clin Hypertens (Greenwich). 2018;20(12):1731-8. DOI:10.1111/jch.13413
________________________________________________
1. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. NCD Risk Factor Collaboration (NCD-RisC). Lancet. 2017;389(10064):37–55. DOI:10.1016/S0140-6736(16)31919-5
2. Forouzanfar MH, Liu P, Roth GA, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317:165-82. DOI:10.1001/jama.2016.19043
3. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017:
a systematic analysis for the Global Burden of Disease Study 2017. GBD 2017 Risk Factor Collaborators. Lancet. 2018;392(10159):1923-94. DOI:10.1016/S0140-6736(18)32225-6
4. Mills KT, Bundy JD, Kelly TN, et al. Global disparities of hypertension prevalence and control: A systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441-50. DOI:10.1161/CIRCULATIONAHA.115.018912
5. Kobalava ZhD, Konradi AO, Nedogoda SV, et al. Arterialnaia gipertenziia u vzroslykh. Klinicheskie rekomendatsii 2020. Rossiiskii kardiologicheskii zhurnal. 2020;25(3):149-218 (in Russian) DOI:10.15829/1560-4071-2020-3-3786
6. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension.
J Hypertens. 2018;36(10):1953-2041. DOI:10.1097/HJH.0000000000001940
7. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension global hypertension practice guidelines. Hypertension. 2020;75(6):1334-57. DOI:10.1161/HYPERTENSIONAHA.120.15026
8. Wright JT Jr, Williamson JD, et al (SPRINT Research Group). A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-16. DOI:10.1056/NEJMoa1511939
9. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387:957-67. DOI:10.1016/S0140-6736(15)01225-8
10. Staessen JA, Thijisq L, Fagard R, et al. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial. J Hypertens. 2004;22(4):847-57. DOI:10.1097/00004872-200404000-00029
11. Sica DA. The valsartan antihypertensive long-term use evaluation trial: a study in contrasts. Hypertension. 2006;48:362-3. DOI: 10.1161/01.HYP.0000236117.13311.0f
12. Tajeu GS, Kent ST, Huang L, et al. Antihypertensive medication nonpersistence and low adherence for adults <65 years initiating treatment in 2007–2014. Hypertension. 2019;74(1):35-46. DOI:10.1161/HYPERTENSIONAHA.118.12495
13. Tajeu GS, Kent ST, Kronish IM, et al. Trends in antihypertensive medication discontinuation and low adherence among medicare beneficiaries initiating treatment from 2007 to 2012. Hypertension. 2016;68(3):565-75.
DOI:10.1161/HYPERTENSIONAHA.116.07720
14. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-324. DOI:10.1161/HYP.0000000000000066
15. World Health Organization Model List of Essential Medicines: 21st List 2019. Geneva: World Health Organization, 2019.
16. Salam A, Kanukula R, Hariprasad E, et al. An application to include blood pressure lowering drug fixed dose combinations to the model list of essential medicines lists for the treatment of essential hypertension in adults. Geneva: World Health Organization, 2019.
17. 2018 Chinese guidelines for prevention and treatment of hypertension – a report of the revision committee of Chinese guidelines for prevention and treatment of hypertension. Joint Committee for Guideline Revision. J Geriatr Cardiol. 2019;16(3):182-241. DOI:10.11909/j.issn.1671-5411.2019.03.014
18. Guidelines on the management of arterial hypertension and related comorbidities in Latin America. Task Force of the Latin American Society of Hypertension. J Hypertens. 2017;35(8):1529-45. DOI:10.1097/HJH.0000000000001418
19. Wald DS, Law M, Morris JK, et al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122(3):290-300. DOI:10.1016/j.amjmed.2008.09.038
20. Shina SK. Monotherapy versus combination therapy for the initial treatment of hypertension. J Clin Prev Cardiol. 2020;9(2):78-83. DOI:10.4103/JCPC.JCPC_27_20
21. DiPette DJ, Skeete J, Ridley E, et al. Fixed-dose combination pharmacologic therapy to improve hypertension control worldwide: clinical perspective and policy implications. J Clin Hypertens (Greenwich). 2019;21(1):4-15. DOI:10.1111/jch.13426
22. Tsioufisa K, Kreutzb R, Sykarac G, et al. Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature. J Hypertens. 2020;38(6):1016-28. DOI:10.1097/HJH.0000000000002381
23. Egan BM, Bandyopadhyay D, Shaftman SR, et al. Initial monotherapy and combination therapy and hypertension control the first year. Hypertension. 2012;59(6):1124-31. DOI:10.1161/HYPERTENSIONAHA.112.194167
24. Mallat SG, Tanios BY, Itani HS, et al. Free versus fixed combination antihypertensive therapy for essential arterial hypertension: a systematic review and meta-analysis. PLoS One. 2016;11(8):e0161285. DOI:10.1371/journal.pone.0161285
25. Parati G, Kjeldsen S, Coca A, et al. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis. Hypertension. 2021;77(2):692-705. DOI:10.1161/HYPERTENSIONAHA.120.15781
26. Salam A, Kanukul R, Atkins E, et al. Efficacy and safety of dual combination therapy of blood pressure-lowering drugs as initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(9):1768-74. DOI:10.1097/HJH.0000000000002096
27. Tung YC, Huang YC, Wu LS, et al. Medication compliance and clinical outcomes of fixed-dose combinations vs free combinations of an angiotensin II receptor blocker and a calcium channel blocker in hypertension treatment. J Clin Hypertens (Greenwich). 2017;19(10):983-9. DOI:10.1111/jch.13035
28. Ho CT, Tung YC, Chou SH et al. Clinical outcomes in hypertensive patients treated with a single-pill fixed-dose combination of renin-angiotensin system inhibitor and thiazide diuretic. J Clin Hypertens (Greenwich). 2018;20(12):1731-8. DOI:10.1111/jch.13413
Авторы
М.В. Леонова*
Межрегиональная общественная организация «Ассоциация клинических фармакологов», Россия
*anti23@mail.ru
________________________________________________
Marina V. Leonova*
Interregional Public Organization "Association of Clinical Pharmacologists", Russia
*anti23@mail.ru