Comparative 24-hour antihypertensive effect of losartan and hydrochlorothiazide as monotherapy or in combination in primary hypertensive patients

Abstract

The purpose of this study was to examine 24-hour antihypertensive effects of losartan as monotherapy or in combination with low dose hydrochlorothiazide and the effects of these medications on circadian blood pressure variation in dippers/nondippers hypertensive patients by using 24-hour ambulatory blood pressure monitoring (ABPM) machine. The study was achieved in thirty-two mild to moderate primary hypertensive patients in out-patient department at King Chulongkorn Memorial Hospital. After one week placebo run-in period or on placebo for at least 5 T1/2 to wash out of any previously taken antihypertensive drugs, mild to moderate hypertensive patients whose office systolic blood pressure (SBP) 140-179 mmHg or diastolic blood pressure (DBP) 90-110 mmHg and mean daytime ambulatory BP>=130-80 mmHg were allocated to receive 12.5 mg dose of HCTZ or losartan 50 mg once daily for 4 weeks and cross over for another 4 weeks. After 8 weeks, patients were categorized to losartan 50 mg normalized group (office SBP/DBP<140/90 mmHg) and losartan 50 mg non-normalized group. Patients in losartan normalized group were randomly allocated to receive either losartan 25 mg or half tablet of losartan 50 mg plus HCTZ12.5 mg once daily. Either losartan 100 mg or one tablet of losartan 50 mg plus HCTZ 12.5 mg once daily were prescribed to losartan non-normalized patients for another 4 weeks. The office blood pressure and the ambulatory blood pressure were monitored at the end of each period. Losartan 50 mg significantly reduced blood pressure of the patients throughout 24 hours while hydrochlorothiazide 12.5 mg could reduce office blood pressure only. Losartan 50 mg also induced higher reduction in BP loads when compared to hydrochlorothiazide 12.5 mg whether considering the frequency, magnitude or AUC above the normal range. Besides, with losartan 50 mg, the circadian rhythm of blood pressure of nondippers might be transformed to dipper patterns. In losartan 50 mg normalized group, decreasing dosage of losartan to 25 mg could reduce blood pressure to nearly the same extent as losartan 50 mg. In losartan 50 mg non-normalized group, increasing the dosage of losartan to 100 mg produce only small further reduction of blood pressure while using the combination of losartan 50 mg plus hydrochlorothiazide 12.5 mg could induce more pronounded further antihypertensive effects. Greater rate of response and higher percentage of normalized patients were also found after treatment with the combination drugs as compared to the increased doses of the single drug. Using ABPM machine could demonstrate the antihypertensive effects of the drug more thoroughly than the office measurement. T:P ratio varied extensively among individual patients. After losartan 50 mg or losartan 50 mg plus hydrochlorothiazidel 12.5 mg once daily, the T:P ratio was ranged 39 to 52%, while the T:P ratio obtained after hydrochlorothiazide 12.5 mg once daily was ranged 31 to 33%. The antihypertensive effects were generatedwithout the reflex tachycardia or intolerance effects or even cough