• European heart journal · Dec 2020

    Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial.

    Taking oral antihypertensive agents at bedtime rather than the morning, improves BP control and reduces the incidence of cardiac death, myocardial infarct, revascularization, heart failure and stroke.

    • Ramón C Hermida, Juan J Crespo, Manuel Domínguez-Sardiña, Alfonso Otero, Ana Moyá, María T Ríos, Elvira Sineiro, María C Castiñeira, Pedro A Callejas, Lorenzo Pousa, José L Salgado, Carmen Durán, Juan J Sánchez, José R Fernández, Artemio Mojón, Diana E Ayala, and Hygia Project Investigators.
    • Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC), University of Vigo, E.I. Telecomunicación, Campus Universitario, Vigo 36310, Spain.
    • Eur. Heart J. 2020 Dec 21; 41 (48): 4565-4576.

    AimsThe Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.Methods And ResultsIn this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].ConclusionRoutine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.Trial RegistrationClinicalTrials.gov, number NCT00741585.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.

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    Taking oral antihypertensive agents at bedtime rather than the morning, improves BP control and reduces the incidence of cardiac death, myocardial infarct, revascularization, heart failure and stroke.

    Daniel Jolley  Daniel Jolley


    Although anti-hypertension therapies are the domain of primary care physicians, because of their widespread use they are common medications for hospital patients. Previous studies have shown that nocturnal anti-hypertensive dosing improves BP control, although have not addressed major cardiac outcomes.

    This 10-year, large, multicenter RCT demonstrates benefit of evening medication dosing that has implications perioperatively.

    The study...

    The Hygia Project randomised 19,084 patients (x̄=61y 56%♂ 34%♀) to take their anti-hypertensive medications (≥1) either at bed-time or on awakening. Patients were followed for a median 6.3 years, routinely using 48h ambulatory BP monitoring at each follow-up review.

    They found that...

    Patients taking anti-hypertensives in the evening experienced better BP control and 45% lower rates of major cardiovascular outcomes, including CVD death, infarct, coronary revascularisation, heart failure and stroke.

    Interestingly the progressive decline in sleeping SBP during the study was the strongest predictor of cardiovascular risk, stronger than traditional risk markers such as age, gender, DM, CKD, cholesterol or even smoking!

    Practice changing?

    This is a significant finding from a large, high-quality study. It confirms the benefits of nocturnal dosing, also likely (though unconfirmed) to have intraoperative and perioperative benefits compared with morning dosing.

    Daniel Jolley  Daniel Jolley
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