Administration time-dependent effects of torasemide on ambulatory blood pressure in patients with essential hypertension

Abstract

Torasemide is a high ceiling loop diuretic frequently used for treatment of congestive heart failure and hypertension [Drug Saf. 1996;14:104–120]. Low doses of torasemide (2.5 to 5 mg/day) do not elevate 24h natriuresis, but they constitute effective once-daily monotherapy for mild-to-moderate uncomplicated essential hypertension [J Hum Hypertens. 2002;16:S78–S83). These results have been mainly based on clinic blood pressure (BP) measurements, without proper evaluation of the 24h efficacy of the drug. On the other hand, diuretics have not yet been studied in relation to possible circadian variation of effects. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of torasemide in hypertensive patients. We studied 55 previously untreated patients with grade 1-2 essential hypertension (25 men), 48.7 ± 11.9 years of age, randomly assigned to receive torasemide (5 mg/d) as a monotherapy either upon awakening or at bedtime. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 hours before and after 6 weeks of therapy. Efficacy of torasemide was significantly higher after bedtime dosing (11.2 and 8.0 mm Hg reduction in the 24-hour mean of systolic and diastolic BP, respectively) as compared to the administration of the drug on awakening (6.2 and 3.7 mm Hg reduction in systolic and diastolic BP). The percentage of patients with controlled ambulatory BP after treatment was also higher after bedtime treatment (52 versus 28%, P=0.042). The time-response curves indicate a full 24h therapeutic coverage only when torasemide was administered before bedtime, with a significant higher efficacy of bedtime dosing as compared to morning treatment after the first 7 hours post-dosing. The 24h urinary secretion of sodium and potassium remained unchanged after treatment for both groups. A single dose of 5 mg/day torasemide is effective for BP reduction mainly after bedtime administration, The differences in efficacy and therapeutic coverage as a function of the circadian time of treatment with torasemide here documented should be taken into account when prescribing this loop diuretic for treatment of patients with essential hypertension.