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Int J Clin Exp Med. 2015 Oct 15;8(10):19156-61. eCollection 2015.

Administration time-dependent effects of combination therapy on ambulatory blood pressure in hypertensive subjects.

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Southern Medical UniversityGuangzhou 510515, Guangdong, China; The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010050, Inner Mongolia, China.
The Affiliated Hospital of Inner Mongolia Medical University Hohhot 010050, Inner Mongolia, China.
Southern Medical UniversityGuangzhou 510515, Guangdong, China; Cardiovascular Internal Medicine of Guangzhou Military General HospitalGuangzhou 510010, Guangdong, China.


The aim of this study was to explore the influence of combination therapy in different administration time on antihypertensive efficacy and blood pressure variability in patients with essential hypertension. A total of 86 patients with stage II to III essential hypertension were randomly divided into 4 groups: taking indapamide and losartan potassium together in the morning or in the evening 2 to 4 hours before sleep, indapamide in the morning and losartan potassium in the evening, losartan potassium in the morning and indapamide in the evening. Ambulatory blood pressure monitoring was performed before and 12 weeks after the medication. The result showed that statistically significant reductions from baseline of systolic blood pressure/diastolic blood pressure occurred in all treatment groups. There was no significant difference of the reductions or SI among the four groups, neither the rate of decline of BP in the night or the circadian rhythm. In group B, the numbers of rapid rise in BP in the morning hours were significantly less after the medication, while not in the other groups. It is concluded that independent of the administration time, both once-daily treatment and component-based dual therapy had significant antihypertensive effect, but the night taken-together combination resulted in reductions of BP, SI and morning blood pressure peak that may have advantages over the other combinations, without the increased incidence of hypotension at night. Medicines should be taken 2 to 4 hours before sleep.


Hypertension; chronotherapy; indapamide; losartan potassium; therapeutic efficacy


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