Comparative effects of morning versus evening amlodipine treatment on blood pressure in patients with mild-to-moderate essential hypertension

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Amlodipine, a calcium antagonist of the 1,4-dihydropyridine type, has been shown to be effective in reducing blood pressure (BP) throughout the day and night when given once daily. However, the potential differing effects on BP of amlodipine given at different times of the day have only been addressed occasionally. We investigated the administration-time dependent antihypertensive efficacy of amlodipine in patients with essential hypertension. We studied 48 patients with mild-to-moderate essential hypertension (35 men and 13 women), 53.4±10.1 (mean±SD) years of age, randomly assigned to receive a single daily dose of amlodipine (5 mg/day) either on awakening or before bedtime. BP was measured at 20-minute intervals during the day (07:00 to 23:00 hours) and at 30-minute intervals at night for 48 consecutive hours at baseline and after 3 months of therapeutic intervention. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. Circadian parameters obtained for each group of patients before and after intervention by population multiple-components analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204] were compared with a paired nonparametric test. After 3 months of therapy with amlodipine, the reduction in BP was similar and highly statistically significant when the drug was administered either on awakening or before bedtime (about 7 and 5 mm Hg reduction in the 24-hour mean of systolic and diastolic BP, respectively; P<0.002 in all cases). This BP reduction was similar during both daytime activity and nighttime resting hours, independently of the dosing time. The smoothness index was 2.8 and 3.4 for systolic and diastolic BP when amlodipine was taken on awakening, with corresponding values of 3.3 and 2.6 for systolic and diastolic BP, respectively, when amlodipine was taken before bedtime. The results demonstrate that, independently of the administration-time with respect to the rest-activity cycle of each individual patient, a single daily dose of amlodipine efficiently reduces BP for the whole 24 hours of the day without affecting the circadian pattern of BP variability in patients with mild-to-moderate essential hypertension.