systhiperСистемные гипертензииSystemic Hypertension2075-082X2542-2189LLC «ИнтерМедсервис»systhiper-463Research ArticleКАРДИОЛОГИЯCARDIOLOGYИзучение возможностей хронотерапии при назначении фиксированной комбинации периндоприла 10 мг и индапамида 2,5 мг (Нолипрел А Би-форте) у пациентов с недостаточной степенью снижения артериального давления в ночное времяChronotherapy’s opportunities of a fixed combination of perindopril 10 mg/indapamide 2.5 mg in patients with a lack of night reduction in blood pressureАксеноваА. В.AksenovaA. V.noemail@neicon.ruЕлфимоваЕ. М.ElfimovaE. M.noemail@neicon.ruЛитвинА. Ю.LitvinA. Yu.alelitvin@yandex.ruЧазоваИ. Е.ChazovaI. E.chazova@hotmail.comИнститут клинической кардиологии им. А.Л.Мясникова ФГБУ Российский кардиологический научно-производственный комплекс Минздрава РоссииРоссияA.L.Myasnikov Institute of Clinical Cardiology, Russian Cardiological Scientific-Industrial Complex of the Ministry of Health of the Russian FederationRussian Federation2016231220221323745Copyright © Аксенова А.В., Елфимова Е.М., Литвин А.Ю., Чазова И.Е., 20222022Аксенова А.В., Елфимова Е.М., Литвин А.Ю., Чазова И.Е.Aksenova A.V., Elfimova E.M., Litvin A.Y., Chazova I.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.syst-hypertension.ru/jour/article/view/463

В настоящее время важной остается проблема адекватного снижения уровня артериального давления (АД) в ночное время у больных артериальной гипертензией. Изучение возможностей хронотерапии при однократном приеме антигипертензивных препаратов в сутки позволит достичь более полного контроля АД при сохранении высокой приверженности лечению. Цель: оценить эффективность, переносимость, безопасность разных режимов назначения фиксированной комбинации периндоприл 10 мг/индапамид 2,5 мг (Нолипрел А Би-форте, «Сервье», Франция) у пациентов с недостаточной степенью снижения АД в ночное время. Дизайн и методы. В исследовании участвовали 30 пациентов (20 мужчин и 10 женщин, 56±9,3 года, индекс массы тела 30,5±5,3 кг/м2, продолжительность наличия артериальной гипертензии 7,1±5,8 года) на неэффективной двухкомпонентной и более антигипертензивной терапии (АД>140/90 мм рт. ст.). Исходно проводились суточное мониторирование АД (СМАД), анализы крови. Затем предыдущая терапия отменялась и назначалась фиксированная комбинация периндоприл 10 мг/индапамид 2,5 мг (Нолипрел А Би-форте). Пациенты рандомизовались в 2 группы: утреннего и вечернего режимов приема терапии. После 8 нед лечения вновь были проведены СМАД и анализы крови. Статистический анализ проводился после дополнительного разделения пациентов на группы с достаточной («дипперы») и недостаточной («нон-дипперы») степенями снижения АД в ночное время. Результаты. В группе «нон-дипперов» уровень среднедневного систолического АД (САД) снизился с 149,4±11,7 до 129,8±10,6 мм рт. ст. (p<0,01), среднедневного диастолического АД (ДАД) - с 94,7±12,3 до 78,3±8,6 мм рт. ст. (ns), средненочного САД - со 146,6±16,1 до 121,8±15,7 мм рт. ст. (p<0,01), средненочного ДАД - с 86,2±9,2 до 70,3±6,5 мм рт. ст. (p<0,01). Степень ночного снижения (СНС) САД увеличилась с 1,9±5,8 до 6,2±9,3% (p<0,05), СНС ДАД - с 6,2±3,9 до 9,6±8,2% (ns). Значения СМАД «нон-дипперов» в группах вечернего и утреннего приема терапии через 2 мес терапии статистически достоверно не отличались между собой, кроме показателя вариабельности дневного ДАД (p<0,05). Статистически недостоверной была разница в показателях СНС АД. Однако и СНС САД, и СНС ДАД были выше в группе вечернего приема препарата: СНС САД 4,1±11,1% и СНС ДАД 8,9±11,0% - в группе утреннего приема препарата и 7,8±7,9% и 10,2±5,5% соответственно - в группе вечернего приема. Анализы крови за время исследования оставались в пределах нормальных значений. Заключение. Фиксированная комбинация периндоприл 10 мг/индапамид 2,5 мг (Нолипрел А Би-форте) эффективна и безопасна у пациентов как с нормальной, так и с недостаточной степенью снижения АД в ночное время. Назначение препарата в вечернее время у пациентов-«нон-дипперов» может иметь дополнительные преимущества влияния на суточный профиль АД. Необходимо проведение дальнейших исследований.

Currently, adequate reduction of blood pressure (BP) during the night in patients with arterial hypertension remains important problem. To study chronotherapy’s opportunities to achieve better BP control by a single dose of antihypertensive drugs while maintaining high compliance. Aim. To evaluate the efficacy, tolerability, safety of various prescription regimes of fixed combination: perindopril 10 mg and indapamide 2.5 mg in patients with insufficient degree of BP reduction at night. Design and methods. The study included 30 patients (20 men and 10 women, 56±9.3 years, body mass index 30.5±5.3 kg/m2, the duration of arterial hypertension - 7.1±5.8 years), on ineffective dual antihypertensive therapy (BP>140/90 mm Hg). Initially, ambulatory BP monitoring (ABPM) and blood tests were performed. Then, previous therapy was terminated and fixed combination of perindopril 10 mg/indapamide 2.5 mg (Noliprel A Bi-forte) was administered. Patients were randomized into two groups: morning and evening regimens of therapy. After 8 weeks of treatment ABPM and blood tests were repeated. Statistical analysis was done after further separation of patients into groups with sufficient (dippers) and insufficient (non-dippers) degree of BP reduction at night. Results. In the group of "non-dippers" average ambulatory systolic BP (SBP) during wakefulness declined from 149.4±11.7 mm Hg to 129.8±10.6 mmHg (p<0.01), the average ambulatory diastolic BP (DBP) during wakefulness - from 94.7±12.3 mm Hg to 78.3±8.6 mm Hg (ns), ambulatory SBP during sleep - from 146.6±16.1 mm Hg to 121.8±15.7 mm Hg (p<0.01), ambulatory DBP during sleep - from 86.2±9.2 mm Hg to 70.3±6.5 mm Hg (p<0.01). The reduction of nighttime SBP increased from 1.9±5.8% to 6.2±9.3% (p<0.05), the reduction of nighttime DBP from 6.2±3.9% to 9.6±8.2% (ns). ABPM measurements of "non-dipper" sub-groups, who received treatment in the evening or in the morning after 2 months had no significant difference, except the variability of DBP during wakefulness (p<0.05). We didn’t observe statistically significant difference in terms of the nighttime BP reduction. However, nighttime BP reduction was higher in the evening dosing group: SBP - 4.1±11.1% (morning group), 7.8±7.9% (evening group) and DBP - 8.9±11.0 (morning group) and 10.2±5.5 (evening group). Blood tests were in the normal range during the whole study. Conclusion. A fixed combination of perindopril 10 mg/indapamide 2.5 mg (Noliprel A Bi-forte) is effective and safe in patients with both normal and with insufficient degree of reduction in BP at night. Prescription of medication in the evening in non-dipper patients can have the added benefit on the BP profile. Further research is needed.

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