Ulyanovsk Medico-biological Journal

CLINICAL MEDICINE

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DOI 10.34014/2227-1848-2023-3-67-78

PROSPECTS FOR INITIAL TRIPLE ANTIHYPERTENSIVE THERAPY

T.O. Okorokova1, O.N. Kryuchkova2

1 Kerch hospital № 1 named after N.I. Pirogov, Kerch, Russia;

2 V.I. Vernadsky Crimean Federal University, Simferopol, Russia

 

The currently recommended initial dual antihypertensive therapy (AHT) results in poor blood pressure (BP) control, whereas most patients should undergo triple-combination therapy to achieve target levels. We have found only foreign publications concerning initial triple antihypertensive treatment.

The aim of the study is to compare the traditional step by step strategy of drug administration and application of three antihypertensive drugs simultaneously.

Materials and Methods. Trial subjects were divided into 2 groups: patients who received conventional dual therapy followed by a third drug agent (n=59) and patients who received initial triple AHT (n=57). The frequency of prescribed drugs and their dosage were comparable. The examination was carried at hospital according to the current standards of medical care for hypertensive adults. Values <140/90 mm Hg were taken as BP target level. Office blood pressure was tested 1 and 3 months after the therapy. 24-hour BP control was carried out 12 weeks after treatment.

Results. The analysis of cardiovascular risks (CVRs) did not reveal significant intergroup differences (p>0.05). Both treatment regimens demonstrated fewer complaints and a comparable frequency of adverse reactions (p>0.05). Intergroup comparison conducted 1 month after treatment showed lower SBP and DBP levels (p<0.001) and a significant decrease in blood pressure in the 2nd group compared to baseline (p<0.001). The chance of achieving BP target level with the traditional scheme was 0.20, while with the initial triple AHT it was 2.35. The odds ratio was 11.53 (95 % CI 4.76; 27.96).

Conclusion. Initial triple antihypertensive therapy has an advantage over the conventional one due to faster achievement of BP target levels. Given the comparable efficacy and frequency of adverse reactions, the strategy may be of interest for further study and implementation in practical medicine.

Key words: hypertension, initial antihypertensive therapy, triple therapy, blood pressure.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Okorokova T.O., Kryuchkova O.N.

Literature search, participation in the research study, data processing: Okorokova T.O., Kryuchkova O.N.

Statistical data processing: Okorokova T.O.

Data analysis and interpretation: Okorokova T.O., Kryuchkova O.N.

Text writing and editing: Okorokova T.O., Kryuchkova O.N.

 

References

  1. Kobalava Zh.D., Konradi A.O., Nedogoda S.V. Arterial'naya gipertenziya u vzroslykh. Klinicheskie rekomendatsii 2020 [Arterial hypertension in adults. Clinical guidelines 2020]. Rossiyskiy kardiologicheskiy zhurnal. 2020; 25 (3): 3786 (in Russian).

  2. Rossiyskoe kardiologicheskoe obshchestvo. Proekt klinicheskikh rekomendatsiy 2022. Arterial'naya gipertenziya u vzroslykh [Russian Society of Cardiology. Draft of clinical guidelines 2022. Arterial hypertension in adults]. Available at: https://scardio.ru/news/novosti_obschestva/proekt_rekomendaciy_po_arterialnoy_gipertenzii_u_vzroslyh/ (accessed: May 03, 2023) (in Russian).

  3. Williams B., Mancia G., Spiering W., eds. ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur. Heart J. 2018; 39: 3021–3104.

  4. Chobanian A.V., Bakris G.L., Black H.R., eds. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003; 289 (19): 2560–2572.

  5. Salam A., Kanukula R., Atkins E., eds. 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): 1768–1774. DOI: 10.1097/HJH.0000000000002096.

  6. Selak V., Webster R., Stepien S., eds. Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials. Heart. 2019; 105 (1): 42–48.

  7. Webster R., Patel A., Selak V., eds. Effectiveness of fixed dose combination medication (‘polypills’) compared with usual care in patients with cardiovascular disease or at high risk: a prospective, individual patient data meta-analysis of 3140 patients in six countries. Int J Cardiol. 2016; 205: 147–156.

  8. Law M.R., Wald N.J., Morris J.K., Jordan R.E. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003; 326 (7404): 1427.

  9. Drawz P.E., Pajewski N.M., Bates J.T., eds. Effect of intensive versus standard clinic-based hypertension management on ambulatory blood pressure: results from the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory blood pressure study. Hypertension. 2017; 69 (1): 42–50.

  10. Atkins E.R., Chow C.K. Low-Dose Combination Therapy for Initial Treatment of Hypertension. Curr Hypertens Rep. 2020; 22 (9): 65.

  11. Mahmud A., Feely J. Low-dose quadruple antihypertensive combination. Hypertension. 2007; 49 (2): 272–275.

  12. Chow C.K., Thakkar J., Bennett A., eds. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. Lancet. 2017; 389 (10073): 1035–1042.

  13. Webster R., Salam A., de Silva H., eds. Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial. JAMA. 2018; 320 (6): 566–579.

  14. Munoz D., Uzoije P., Reynolds C., eds. Polypill for cardiovascular disease prevention in an underserved population. N Engl J Med. 2019; 381 (12): 1114–1123.

  15. Chow K.C., Atkins E.R., Hillis G.S., eds. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. The Lancet. 2021; 398 (10305): 1043–1052.

  16. Chow C.K., Atkins E.R., Billot L., eds. Ultra-low-dose quadruple combination blood pressure-lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol. Am Heart J. 2021; 231: 56–67.

  17. Baldridge A.S., Huffman M.D., Lazar D., eds. Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial. Am Heart J. 2022; 254: 183–193.

  18. O'Hagan E.T., McIntyre D., Nguyen T., Chow C.K. Hypertension therapy using fixed-dose polypills that contain at least three medications. Heart. 2023; 21. Available at: https://heart.bmj.com/content/early/2023/02/20/heartjnl-2022-321496.long (accessed: May 8, 2023). DOI: 10.1136/heartjnl-2022-321496.

  19. Bergler-Klein J. What's new in the ESC 2018 guidelines for arterial hypertension: The ten most important messages. Wien Klin Wochenschr. 2019; 131 (7): 180–185.

  20. Mancia G., Parati G., Bilo G., Choi J., eds. Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study. J Hypertens. 2011; 29 (3): 600–609.

 

Received May 13, 2023; accepted May 21, 2023.

 

Information about the authors

Okorokova Tat'yana Olegovna, Cardiologist, Kerch Hospital № 1 named after N.I. Pirogov. 298302, Russia, Kerch, Zh. Dudnik St., 1; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-8888-8168

Kryuchkova Ol'ga Nikolaevna, Doctor of Sciences (Medicine), Professor, Chair of Therapy, Gastroenterology, Cardiology and General Medical Practice (Family Medicine), Medical Academy named after S.I. Georgievsky, V.I. Vernadsky Crimean Federal University. 295051, Russia, Simferopol, Lenin Blvd., 5/7; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0350-6843

 

For citation

Okorokova T.O., Kryuchkova O.N. Perspektivy ispol'zovaniya startovoy troynoy antigipertenzivnoy terapii [Prospects for initial triple antihypertensive therapy]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023; 3: 67–78. DOI: 10.34014/2227-1848-2023-3-67-78 (in Russian).

 

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УДК 616.12-008.331.1

DOI 10.34014/2227-1848-2023-3-67-78

ПЕРСПЕКТИВЫ ИСПОЛЬЗОВАНИЯ СТАРТОВОЙ ТРОЙНОЙ АНТИГИПЕРТЕНЗИВНОЙ ТЕРАПИИ

Т.О. Окорокова1, О.Н. Крючкова2

1 ГБУЗ РК «Керченская больница № 1 им. Н.И. Пирогова», г. Керчь, Россия;

2 ФГАОУ ВО «Крымский федеральный университет им. В.И. Вернадского», г. Симферополь, Россия

 

Рекомендуемая в настоящее время стартовая двойная антигипертензивная терапия (АГТ) приводит к низкому уровню контроля артериального давления (АД), а большинству пациентов для достижения целевых уровней требуется назначение минимум трех лекарственных препаратов. В отличие от зарубежных источников отечественные публикации, касающиеся стартовой тройной АГТ, нами не обнаружены.

Цель. Сравнить стратегии традиционного пошагового назначения тройной АГТ и стартового использования трех гипотензивных препаратов.

Материалы и методы. Участники исследования были разделены на 2 группы: пациенты, получавшие традиционную двойную терапию с последующим усилением третьим лекарственным агентом (n=59), и пациенты, получавшие стартовую тройную АГТ (n=57). Частота назначения препаратов, а также дозы лекарственных средств были сопоставимы. Обследование проводилось согласно действующим стандартам медицинской помощи взрослым при АГ в стационаре. За целевой уровень АД принимались значения менее 140/90 мм рт. ст. Уровень офисного АД оценивался через 1 и 3 мес., контроль суточного мониторинга АД проводился спустя 12 нед. лечения.

Результаты. Проведенный анализ факторов сердечно-сосудистого риска не выявил межгрупповых различий (р>0,05). Обе схемы лечения продемонстрировали как снижение частоты жалоб, так и сопоставимую частоту нежелательных побочных реакций (р>0,05). Межгрупповое сравнение через 1 мес. лечения продемонстрировало более низкие уровни САД и ДАД (p<0,001), а также более значимое снижение АД по сравнению с исходным уровнем (p<0,001) во 2-й группе. Шанс достижения контроля АД при применении традиционной схемы составил 0,20, при использовании стартовой тройной АГТ – 2,35. Отношение шансов составило 11,53 (95 % ДИ 4,76; 27,96).

Выводы. Стартовая тройная АГТ имеет преимущество перед традиционным назначением ввиду более быстрого достижения целевых уровней АД. Учитывая сопоставимую эффективность и частоту нежелательных побочных реакций, данная стратегия может представлять интерес для дальнейшего изучения и внедрения в практическую медицину.

Ключевые слова: артериальная гипертензия, стартовая антигипертензивная терапия, тройная терапия, артериальное давление.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Концепция и дизайн исследования: Окорокова Т.О., Крючкова О.Н.

Литературный поиск, участие в исследовании, обработка материала: Окорокова Т.О., Крючкова О.Н.

Статистическая обработка данных: Окорокова Т.О.

Анализ и интерпретация данных: Окорокова Т.О., Крючкова О.Н.

Написание и редактирование текста: Окорокова Т.О., Крючкова О.Н.

 

Литература

  1. Кобалава Ж.Д., Конради А.О., Недогода С.В. Артериальная гипертензия у взрослых. Клинические рекомендации 2020. Российский кардиологический журнал. 2020; 25 (3): 3786.

  2. Российское кардиологическое общество. Проект клинических рекомендаций 2022. Артериальная гипертензия у взрослых. URL: https://scardio.ru/news/novosti_obschestva/proekt_rekomendaciy_po_arterialnoy_gipertenzii_u_vzroslyh/ (дата обращения: 03.05.2023).

  3. Williams B., Mancia G., Spiering W., eds. ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur. Heart J. 2018; 39: 3021–3104.

  4. Chobanian A.V., Bakris G.L., Black H.R., eds. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003; 289 (19): 2560–2572.

  5. Salam A., Kanukula R., Atkins E., eds. 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): 1768–1774. DOI: 10.1097/HJH.0000000000002096.

  6. Selak V., Webster R., Stepien S., eds. Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials. Heart. 2019; 105 (1): 42–48.

  7. Webster R., Patel A., Selak V., eds. Effectiveness of fixed dose combination medication (‘polypills’) compared with usual care in patients with cardiovascular disease or at high risk: a prospective, individual patient data meta-analysis of 3140 patients in six countries. Int J Cardiol. 2016; 205: 147–156.

  8. Law M.R., Wald N.J., Morris J.K., Jordan R.E. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003; 326 (7404): 1427.

  9. Drawz P.E., Pajewski N.M., Bates J.T., eds. Effect of intensive versus standard clinic-based hypertension management on ambulatory blood pressure: results from the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory blood pressure study. Hypertension. 2017; 69 (1): 42–50.

  10. Atkins E.R., Chow C.K. Low-Dose Combination Therapy for Initial Treatment of Hypertension. Curr Hypertens Rep. 2020; 22 (9): 65.

  11. Mahmud A., Feely J. Low-dose quadruple antihypertensive combination. Hypertension. 2007; 49 (2): 272–275.

  12. Chow C.K., Thakkar J., Bennett A., eds. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. Lancet. 2017; 389 (10073): 1035–1042.

  13. Webster R., Salam A., de Silva H., eds. Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial. JAMA. 2018; 320 (6): 566–579.

  14. Munoz D., Uzoije P., Reynolds C., eds. Polypill for cardiovascular disease prevention in an underserved population. N Engl J Med. 2019; 381 (12): 1114–1123.

  15. Chow K.C., Atkins E.R., Hillis G.S., eds. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. The Lancet. 2021; 398 (10305): 1043–1052.

  16. Chow C.K., Atkins E.R., Billot L., eds. Ultra-low-dose quadruple combination blood pressure-lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol. Am Heart J. 2021; 231: 56–67.

  17. Baldridge A.S., Huffman M.D., Lazar D., eds. Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial. Am Heart J. 2022; 254: 183–193.

  18. O'Hagan E.T., McIntyre D., Nguyen T., Chow C.K. Hypertension therapy using fixed-dose polypills that contain at least three medications. Heart. 2023; 21. URL: https://heart.bmj.com/content/early/2023/02/20/heartjnl-2022-321496.long (дата обращения: 08.05.2023). DOI: 10.1136/heartjnl-2022-321496.

  19. Bergler-Klein J. What's new in the ESC 2018 guidelines for arterial hypertension: The ten most important messages. Wien Klin Wochenschr. 2019; 131 (7): 180–185.

  20. Mancia G., Parati G., Bilo G., Choi J., eds. Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study. J Hypertens. 2011; 29 (3): 600–609.

 

Поступила в редакцию 13.05.2023; принята 21.05.2023.

 

Авторский коллектив

Окорокова Татьяна Олеговна – врач-кардиолог, ГБУЗ РК «Керченская больница № 1 им. Н.И. Пирогова». 298302, Россия, г. Керчь, ул. Ж. Дудник, 1; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-8888-8168

Крючкова Ольга Николаевна – доктор медицинских наук, профессор кафедры терапии, гастроэнтерологии, кардиологии и общей врачебной практики (семейной медицины) Медицинской академии им. С.И. Георгиевского, ФГАОУ ВО «Крымский федеральный университет им. В.И. Вернадского». 295051, Россия, г. Симферополь, б-р Ленина, 5/7; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0350-6843

 

Образец цитирования

Окорокова Т.О., Крючкова О.Н. Перспективы использования стартовой тройной антигипертензивной терапии. Ульяновский медико-биологический журнал. 2023; 3: 67–78. DOI: 10.34014/2227-1848-2023-3-67-78.