Hermida Ramón C, Ayala Diana E, Mojón Artemio, Chayán Luisa, Domínguez María J, Fontao María J, Soler Rita, Alonso Ignacio, Fernandez José R
Bioengineering & Chronobiology Laboratories, University of Vigo, Vigo (Pontevedra), Spain.
Chronobiol Int. 2008 Nov;25(6):950-70. doi: 10.1080/07420520802544589.
Torasemide is a high-ceiling loop diuretic frequently used in the treatment of congestive heart failure, renal failure, and hypertension. Low doses of torasemide (2.5 to 5 mg/day) do not elevate 24 h natriuresis, and they constitute effective monotherapy for mild-to-moderate uncomplicated essential hypertension according to results based on clinic blood pressure (BP). However, there has yet to be a proper evaluation of its 24 h efficacy or potential dependency of effects according to the circadian time of treatment. Accordingly, this trial investigated the administration time-dependent efficacy of torasemide in uncomplicated essential hypertensive patients. We studied a total of 113 grade 1 and 2 hypertensive patients, 51.7+/-10.6 yrs of age, randomly assigned to receive torasemide (5 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours before and after six weeks of treatment. The efficacy of torasemide was significantly greater with bedtime dosing (i.e., 14.8 and 9.5 mmHg reduction in the 24 h mean systolic and diastolic BP, respectively) as compared with morning dosing upon awakening (i.e., 6.4 and 3.4 mmHg reduction in mean systolic and diastolic BP; p<0.001 between the two treatment-time groups). The percentage of patients with controlled ambulatory BP after treatment was also higher after bedtime treatment (64 vs. 23%; p<0.001). Safety and tolerability were comparable between the two treatment-time groups. A dose of 5 mg/day torasemide is more effective for BP reduction for uncomplicated essential hypertensive patients when ingested at bedtime than in the morning upon arising. The difference in antihypertensive efficacy as a function of the circadian dosing-time of torasemide here documented should be taken into account when prescribing this loop diuretic to treat essential hypertensive patients.
托拉塞米是一种高效能袢利尿剂,常用于治疗充血性心力衰竭、肾衰竭和高血压。低剂量托拉塞米(2.5至5毫克/天)不会增加24小时尿钠排泄,根据临床血压(BP)结果,它们构成轻度至中度单纯性原发性高血压的有效单一疗法。然而,尚未根据治疗的昼夜时间对其24小时疗效或效应的潜在依赖性进行适当评估。因此,本试验研究了托拉塞米在单纯性原发性高血压患者中的给药时间依赖性疗效。我们共研究了113例1级和2级高血压患者,年龄51.7±10.6岁,随机分配接受托拉塞米(5毫克/天)单一疗法,要么在醒来时服用,要么在睡前服用。在治疗六周前后,通过动态监测连续48小时测量血压。与醒来时早晨给药相比(即平均收缩压和舒张压分别降低6.4和3.4毫米汞柱),睡前给药时托拉塞米的疗效显著更高(即24小时平均收缩压和舒张压分别降低14.8和9.5毫米汞柱;两个治疗时间组之间p<0.001)。治疗后动态血压得到控制的患者百分比在睡前治疗后也更高(64%对23%;p<0.001)。两个治疗时间组之间的安全性和耐受性相当。对于单纯性原发性高血压患者,每天5毫克托拉塞米在睡前服用时比早晨起床时服用对降低血压更有效。在为原发性高血压患者开这种袢利尿剂时,应考虑此处记录的托拉塞米昼夜给药时间对抗高血压疗效的差异。