Physicians' Academy for Cardiovascular Education

Hypertension medication ingestion at bedtime improves asleep ABP and reduces CVD risk

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

Literature - Hermida RC, Crespo JJ, Domínguez-Sardiña M et al., - Eur Heart J 2019, ehz754, DOI:

Introduction and methods

Multiple prospective studies and meta-analyses have demonstrated that mean asleep BP determined by ambulatory BP monitoring (ABPM) is a more sensitive prognostic marker of CVD compared to daytime office BP measurements, ABPM-derived awake mean, or 24h BP mean [1-6]. It was shown that therapeutically induced reduction of asleep systolic BP (SBP) mean and enhancement of sleep-time relative SBP decline towards a normal dipper pattern result in reduced CVD risk [3,6]. Improved normalization of asleep BP and 24h BP patterning was observed when hypertension medications were ingested at bedtime instead of upon awakening [7,8].

Several studies assessed the effect of bedtime hypertension medication ingestion on CVD risk reduction, however a control group of patients ingesting medication in the morning was missing [7-12]. The MAPEC (Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events) study showed in a small cohort of 2156 hypertensive patients over a median follow-up of 5.6 years that bedtime ingestion of treatment resulted in significantly reduced asleep BP, reduced prevalence of non-dipping, and reduced incidence of CVD events compared to medication intake upon awakening [13]. The current study investigated the effect of timing of hypertension medication ingestion on ABP control and CVD risk in a large cohort in a primary care clinical setting.

The Hygia Chronotherapy Trial is a multicenter, controlled, PROBE (prospective, randomized, open-label, blinded endpoint) study with 19084 (10614 men, 8470 women) hypertensive patients aged 60.5 ± 13.7 (mean ± SD) years. Patients were randomized to ingest the entire daily dose of ≥1 prescribed BP medications of the major therapeutic classes (ARB, ACEI, CCB, β-blocker, and/or diuretic) at either bedtime (n=9552) or upon awakening (n=9532). ABP was monitored for 48 h at baseline and each clinic visit (at least once a year). The median follow-up was 6.3 years (IQR 4.1-8.3 years).

The primary CVD outcome was myocardial infarction, coronary revascularization, heart failure, ischemic stroke, hemorrhagic stroke and CVD death.

Main results


This study demonstrated that ingestion of the entire daily dose of hypertension medication at bedtime significantly improved asleep ABP and significantly reduced CVD morbidity and mortality. Time of ingestion of hypertension medication did not affect awake mean BP nor did it affect the prevalence of adverse effects.


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