Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (atlanTTic), University of Vigo, Vigo 36310, Spain; Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX 78712-0238, USA.
Circadian Ambulatory Technology & Diagnostics (CAT&D), Santiago de Compostela, 15703, Spain.
Adv Drug Deliv Rev. 2021 Mar;170:200-213. doi: 10.1016/j.addr.2021.01.013. Epub 2021 Jan 22.
Pharmacokinetics of hypertension medications is significantly affected by circadian rhythms that influence absorption, distribution, metabolism and elimination. Furthermore, their pharmacodynamics is affected by ingestion-time differences in kinetics and circadian rhythms comprising the biological mechanism of the 24 h blood pressure (BP) pattern. However, hypertension guidelines do not recommend the time to treat patients with medications. We conducted a systematic review of published evidence regarding ingestion-time differences of hypertension medications and their combinations on ambulatory BP-lowering, safety, and markers of target organ pathology. Some 153 trials published between 1976 and 2020, totaling 23,869 hypertensive individuals, evaluated 37 different single and 14 dual-fixed combination therapies. The vast (83.7%) majority of the trials report clinically and statistically significant benefits - including enhanced reduction of asleep BP without inducing sleep-time hypotension, reduced prevalence of the higher cardiovascular disease risk BP non-dipping 24 h profile, decreased incidence of adverse effects, improved renal function, and reduced cardiac pathology - when hypertension medications are ingested at-bedtime/evening rather than upon-waking/morning. Non-substantiated treatment-time difference in effects by the small proportion (16.3%) of published trials is likely explained by deficiencies of study design and conduct. Systematic and comprehensive review of the literature published the past 45 years reveals no single study reported significantly better benefit of the still conventional, yet unjustified by medical evidence, upon-waking/morning hypertension treatment schedule.
高血压药物的药代动力学受到昼夜节律的显著影响，这些节律会影响吸收、分布、代谢和消除。此外，它们的药效学受到动力学和昼夜节律的摄入时间差异的影响，这些差异构成了 24 小时血压（BP）模式的生物学机制。然而，高血压指南并没有建议根据时间来为患者治疗高血压。我们对已发表的关于高血压药物及其组合的摄入时间差异对动态血压降低、安全性和靶器官病理标志物的影响的证据进行了系统评价。1976 年至 2020 年期间发表的约 153 项试验，共涉及 23869 名高血压患者，评估了 37 种不同的单药和 14 种双固定组合疗法。绝大多数试验（83.7%）报告了临床和统计学上的显著益处，包括在不引起睡眠时低血压的情况下增强对睡眠时血压的降低，降低心血管疾病风险更高的 24 小时血压非杓型模式的发生率，减少不良反应的发生率，改善肾功能和减少心脏病理，当高血压药物在睡前/夜间服用而不是在醒来/早晨服用时。发表的少数试验（16.3%）报告的治疗时间差异无显著效果，这可能是由于研究设计和实施的缺陷所致。对过去 45 年发表的文献进行系统和全面的回顾，没有一项研究报告说，仍在常规使用的早晨高血压治疗方案有明显更好的益处，尽管这没有得到医学证据的支持。
