Bedtime Dosing of Antihypertensive Medications Reduces Cardiovascular Risk in CKD
Bedtime Dosing of Antihypertensive Medications Reduces Cardiovascular Risk in CKD
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DOI：
10.1681/asn.2011040361
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发表时间：
2011-12-01
影响因子：
13.6
通讯作者：
Fernandez, Jose R.
中科院分区：
文献类型：
--
作者：
Hermida, Ramon C.;Ayala, Diana E.;Fernandez, Jose R.
服用高血压药物的时间可以影响血压的昼夜节律模式，但这是否转化为对临床结果的影响尚不清楚。在这里，在一项开放标签试验中，我们随机分配了661名CKD患者，要么在醒来时服用所有处方的高血压药物，要么在睡前服用至少一种药物。我们在基线和治疗调整后3个月或至少每年测量48小时动态血压。经过中位5.4年的随访，睡前服用至少一种降压药物的患者有总心血管事件的校正风险（死亡、心肌梗塞、心绞痛、血管重建、心力衰竭、下肢动脉闭塞、视网膜动脉闭塞，和中风），约为觉醒时服用所有药物的患者的三分之一（校正HR 0.31; 95% CI 0.21 - 0.46; P < 0.001）。睡前给药也显示出类似的心血管死亡、心肌梗死和卒中复合结局风险显著降低（校正HR 0.28; 95%CI 0.13 - 0.61; P < 0.001）。此外，睡前治疗的患者平均睡眠时间血压显著降低，更大比例的患者显示其动态血压得到控制（56%对45%，P = 0.003）。平均睡眠时间收缩压每降低5 mmHg，随访期间心血管事件风险降低14%（P < 0.001）。总之，在CKD和高血压患者中，睡前服用至少一种降压药物可改善血压控制，降低心血管事件风险。
Time of ingestion of hypertension medications can affect circadian patterns of BP, but whether this translates into an effect on clinical outcomes is unknown. Here, in an open-label trial, we randomly assigned 661 patients with CKD either to take all prescribed hypertension medications upon awakening or to take at least one of them at bedtime. We measured 48-hour ambulatory BP at baseline and 3 months after any adjustment in treatment or, at the least, annually. After a median follow-up of 5.4 years, patients who took at least one BP-lowering medication at bedtime had an adjusted risk for total cardiovascular events (a composite of death, myocardial infarction, angina pectoris, revascularization, heart failure, arterial occlusion of lower extremities, occlusion of the retinal artery, and stroke) that was approximately one-third that of patients who took all medications upon awakening (adjusted HR 0.31; 95% CI 0.21 to 0.46; P < 0.001). Bedtime dosing demonstrated a similar significant reduction in risk for a composite outcome of cardiovascular death, myocardial infarction, and stroke (adjusted HR 0.28; 95% CI 0.13 to 0.61; P < 0.001). Furthermore, patients on bedtime treatment had a significantly lower mean sleep-time BP and a greater proportion demonstrated control of their ambulatory BP (56% versus 45%, P = 0.003). Each 5-mmHg decrease in mean sleep-time systolic BP was associated with a 14% reduction in the risk for cardiovascular events during follow-up (P < 0.001). In conclusion, among patients with CKD and hypertension, taking at least one antihypertensive medication at bedtime improves control of BP and reduces the risk for cardiovascular events.