COMBINED ANTIHYPERTENSIVE THERAPY: FOCUS ON A FIXED-DOSE COMBINATION OF AN ACE INHIBITOR AND A DIURETIC

The study aimed to assess the effectiveness and safety of a fixed-dose combination of an ACE inhibitor (losartan) and a diuretic (hydrochlorothiazide) in patients with arterial hypertension (AH) and high or very high cardiovascular risk. The study included 30 patients with Stage I-III AH (13 men and 17 women; mean age 51,9±1,9 years). For 12 weeks, the participants were administered a combination of losartan (50 mg) and hydrochlorothiazide (12,5 mg; once a day, in the morning). Echocardiography and 24-hour blood pressure monitoring (BPM) were performed. In 2 and 4 weeks, a reduction in office systolic BP (SBP) and office diastolic BP (DBP), respectively, was observed. In 12 weeks, BP reduction was even more pronounced, with a reduction in 24-hour SBP (from 141,9±1,9 to 128,6±0,8 mm Hg; p<0,001), daytime SBP (from 146,8±2,6 to 135,8±1,0 mm Hg; p><0,01), and nighttime SBP (from 131,5±1,9 to 118,8±1,9 mm Hg; p><0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p><0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,001), daytime SBP (from 146,8±2,6 to 135,8±1,0 mm Hg; p<0,01), and nighttime SBP (from 131,5±1,9 to 118,8±1,9 mm Hg; p><0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p><0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,01), and nighttime SBP (from 131,5±1,9 to 118,8±1,9 mm Hg; p<0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p><0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p<0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p<0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p<0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p<0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p<0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p<0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.

1. Литвин А.Ю. Гипертоническая болезнь и микроальбуминурия//Кардиология 1996; 6, 9: 74-81.

2. Ощепкова Е.В., Рогоза А.Р., Варакин Ю.А. Вариабельность артериального давления (по данным суточного мониторирования) при мягкой артериальной гипертонии// Тер. архив 1994; 8: 7073.

3. Рунихина Н.К., Рогоза А.Н., Вихерт О.А. Суточный профиль артериального давления и структурно-функциональные изменения сердечно-сосудистой системы при начальной стадии гипертонической болезни//Тер. архив 1997; 4: 39-42.

4. Рекомендации по профилактике, диагностике и лечению артериальной гипертензии. Российские рекомендации. Комитет ВНОК. Секция артериальной гипертонии. М, 2001.

5. Рекомендации по профилактике, диагностике и лечению артериальной гипертензии. Российские рекомендации. Комитет ВНОК. Секция артериальной гипертонии. М, 2004.

6. Chobanian A. V., Bakris G.L., Black H.R. et al. 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: 2560-72.

7. Devereux R.B., Pickering T.G., Harshfield G.A. et al. Left ventricular hypertrophy in patients with hypertension: importance of blood pressure response to regulary reccur-ing stress//Circulation 1998; 68: 447-76.

8. Guidelines Sub-Commitee. 1999 World Health Organization – International Society of hypertension guidelines for the management of hypertension//J Hypertens 1999; 17: 151-183.

9. Ljungman S., Wikstrand J., Hartford M. et al. Urinary albumin excretion a predictor of risk of cardiovascular disease. A prospective 10-year follow-up of middle-aged nondiabetic normal and hypertensive men//Am. J. Hypertens. 1996; 9, 8: 770-8.

10. Meredith P.A., Perloff D., Mancia G. et al. Blood pressure variability and its implica-tions for antihypertensive therapy// Blood Press. 1 995; 4: 5-11.

11. Palatini P., Pessina A.C., Graniero G.R. et al. The relationship between overweight, life style and casual and 24-hour pressures in a population of male subjects with mild hypertension. The results of the harvest study// J. Ital. Cardiol. 1 995; 25, 8: 977- 89.

12. Staessen J., Fagard R., Lijnen P. Reference values for ambulatory blood pressure: a metaanalysis// Ibit. 1990; 8, 6: 67-9.

13. 2003 European Society of hypertension – European Society of cardiology guidelines for the management of arterial hypertension//J Hypertens. 2003; 21: 1011 – 53.