Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects

This study investigated the administration time - dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects ( 30 men and 60 women), 49.0 +/- 14.3 ( mean +/- SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan ( 160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan ( P < 0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P > 0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% ( P < 0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.