Bioengineering and Chronobiology Laboratories, University of Vigo, Vigo, Spain.
Chronobiol Int. 2010 Jul;27(6):1287-303. doi: 10.3109/07420528.2010.489167.
Administration of valsartan at bedtime as opposed to upon wakening improves the sleep-time relative blood pressure (BP) decline towards a more normal dipper pattern without loss of 24-h efficacy. Amlodipine, however, has been shown to be effective in reducing BP throughout the day and night, independent of dosing time. A large proportion of hypertensive subjects cannot be properly controlled with a single medication. However, no study has yet investigated the potential differing effects of combination therapy depending of the time-of-day of administration. Accordingly, the authors investigated the administration-time-dependent BP-lowering efficacy of valsartan/amlodipine combination. The authors studied 203 hypertensive subjects (92 men/111 women), 56.7 +/- 12.5 yrs of age, randomized to receive valsartan (160 mg/day) and amlodipine (5 mg/day) in one of the following four therapeutic schemes: both medications on awakening, both at bedtime, either one administered on awakening and the other at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours before and after 12 wks of treatment. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately determine the beginning and end of daytime activity and nocturnal sleep. BP-lowering efficacy (quantified in terms of reduction of the 48-h mean of systolic/diastolic BP) was highest when both hypertension medications were ingested at bedtime, as compared to any one of the three other tested therapeutic schemes (17.4/13.4 mm Hg reduction with both medications on awakening; 15.1/9.6 mm Hg with valsartan on awakening and amlodipine at bedtime; 18.2/12.3 mm Hg with valsartan at bedtime and amlodipine on awakening; 24.7/13.5 mm Hg with both medications at bedtime; p < .018 between groups). The sleep-time relative BP decline was significantly increased towards a more normal dipper pattern only when both medications were jointly ingested at bedtime (p < .001). Bedtime dosing of the combination of the two medications also resulted in the largest percentage of controlled subjects among all the assessed therapeutic schemes (p = .003 between groups). In subjects requiring combination therapy to achieve proper BP control, the association of amlodipine and valsartan efficiently reduces BP for the entire 24 h independent of dosing time. However, the greater proportion of controlled patients, improved efficacy on lowering asleep BP mean, and increased sleep-time relative BP decline suggest valsartan/amlodipine combination therapy should be preferably administered at bedtime.
缬沙坦在睡前给药与在醒来时给药相比，可改善睡眠时的相对血压（BP）下降，使其更接近正常的杓型模式，而不会丧失 24 小时的疗效。然而，氨氯地平已被证明在白天和夜间都能有效降低血压，而与给药时间无关。很大一部分高血压患者不能用单一药物得到适当控制。然而，目前还没有研究表明联合治疗的潜在不同作用取决于给药时间。因此，作者研究了缬沙坦/氨氯地平联合治疗的降压疗效与给药时间的关系。作者研究了 203 名高血压患者（92 名男性/111 名女性），年龄 56.7 +/- 12.5 岁，随机分为以下四种治疗方案中的一种：醒来时同时服用缬沙坦（160mg/天）和氨氯地平（5mg/天），醒来时同时服用缬沙坦和氨氯地平，睡前服用缬沙坦和氨氯地平。在治疗 12 周前和后，通过动态血压监测连续 48 小时测量血压。通过腕部动作计每分钟同时监测身体活动，以准确确定白天活动和夜间睡眠的开始和结束。当两种降压药物都在睡前服用时，降压效果（以 48 小时平均收缩压/舒张压降低的幅度来衡量）最高，与其他三种测试治疗方案中的任何一种相比（醒来时同时服用两种药物时降低 17.4/13.4mmHg；醒来时服用缬沙坦，睡前服用氨氯地平时降低 15.1/9.6mmHg；睡前服用缬沙坦，醒来时服用氨氯地平时降低 18.2/12.3mmHg；睡前同时服用两种药物时降低 24.7/13.5mmHg；组间差异 p <.018）。只有当两种药物同时联合服用时，睡眠时相对血压的下降才会显著增加，更接近正常的杓型模式（p <.001）。两种药物同时睡前给药还导致所有评估治疗方案中控制患者的比例最大（组间差异 p =.003）。对于需要联合治疗以达到适当血压控制的患者，氨氯地平和缬沙坦的联合应用可有效降低 24 小时内的血压，而与给药时间无关。然而，控制患者的比例更大，降低睡眠时平均血压的疗效提高，以及睡眠时相对血压下降的幅度增加，表明缬沙坦/氨氯地平联合治疗最好在睡前给药。
