Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension—Pro Side of the Argument

Abstract

Hermida et al make a good case about the importance of ambulatory blood pressure monitoring and nocturnal hypertension, with which we agree. Otherwise, in their defense of chronotherapy, they rely on their own duplicate publications of the same systematic review (https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020201220), which include a plurality of studies from their own group and are limited by inclusion of cross-sectional, overlapping, and otherwise biased studies. Notably, this review was neither conducted according to the Cochrane methodology nor properly reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Hermida et al continue their inconsistent criticism of other studies with discordant results, casting aspersions on sample size of properly conducted and clearly reported trials (Hellenic-Anglo Research into Morning or Night Antihypertensive Drug Delivery [HARMONY]) and ongoing trials with rigorous protocols (BedMed and TIME [Treatment in Morning Versus Evening]). They accept evening dosing (as opposed to bedtime) when the conclusions align with their own (eg, Roush systematic review) but raise it as a weakness when they do not. More importantly, no further details or explanation are provided for the incredible benefit seen in Hygia for noncardiovascular mortality and the unprecedented lack of adverse effects. The investigation reported by the European Heart Journal editors suggests that Hygia was a low-cost trial embedded in routine care that lacked the robust measurement of adherence, adverse events, and event adjudication typically expected from clinical trials. This is the most plausible explanation for their findings, and the medical community should await the results of more rigorous ongoing clinical trials.

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial

“…The relative pros and cons of evening dosing have been debated, and controversy persists, with some researchers suggesting that the Hygia Chronotherapy Trial might not have been a true randomised controlled trial. 8 , 17 , 18 In the Treatment in Morning versus Evening (TIME) study, we aimed to investigate whether evening dosing of antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension treated with their usual antihypertensive medications.…”

Chronotherapy of hypertension: current state of the problem and prospects

“…Особенности сна и бодрствования, активности и отдыха, потребления пищи и голодания влияют на колебания рН желудочного сока, опустошение желудка, прохождение пищи по желудочно-кишечному тракту, кровоток в органах, активность печеночных ферментов, почечную функцию и как следствие -на биодоступность лекарств и продолжительность их действия через регуляцию абсорбции, распределения, ОБЗОР ЛИТЕРАТУРЫ для бета-адреноблокаторов -в 7 из 7, для диуретиков -в 4 из 5, для альфа-блокаторов -в 3 из 3 [35]. Результаты 20 небольших исследований хронофармакологии АГП суммированы в метаанализе 2011г: показано небольшое, но статистически значимое снижение 24-ч АД при приеме препаратов вечером по сравнению с утром (разница для САД -1,71 мм рт.ст.…”

“…Российский кардиологический журнал 2023; 28 (3) имущества вечернего приема показаны в 23 работах [35]. В исследовании с полипилюлей, содержащей аспирин, симвастатин, лизиноприл и ГХТ не выявлено разницы в значениях 24-ч САД между вечерним и утренним приемом [37].…”

“…и к ХТ аспектам их использования, однако количество исследований, изучавших фиксированные комбинации с позиций хронофармакологии, невелико. Некоторые представлены в таблице 3 [19,22,35]. Из 17 исследований, сравнивавших эффекты утреннего и вечернего приема 14 двойных комбинаций, 16 подтвердили преимущества вечернего назначения.…”

Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…Antihypertensive drugs are some of the most commonly prescribed medications in the United States and worldwide. 1 However, the timing of their administration remains controversial, 2–5 and society guidelines have been silent on this issue. 6,7 Traditionally, antihypertensive drugs are administered in the morning.…”