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

Trial Reference

Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. 2019 Oct 22 [Epub ahead of print].

Abstract | Full Text

Expert Comment

Celso Amodeo, Sao Paulo, Brazil
ISCP Board of Directors


Summary of the Study

The 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 (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke).

This was one of the longest follow-up study undertaken (6.3-year median patient follow-up) to evaluate the time of day to administer the antihypertensive medications.

In brief, the Hygia Project was composed of a network of 40 primary care centers and included 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age). It was a multicentric, controlled, prospective trial, were the patients were assigned (1:1) to take daily dose of >1 antihypertensive medications at bedtime (n = 9552) or all such medications upon awakening (n = 9532). During the follow-up period 1752 participants experienced the primary CVD outcome. Patients of the bedtime-treatment regimen evidenced significantly lower Hazard Rate (HR) of the primary CVD outcome compared with those taking all medications upon awakening [HR= 0.55 (95% CI 0.50–0.61), P< 0.001; Figure 2A].

Therefore, the authors conclude that routine ingestion by hypertensive medications of >1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in markedly diminished occurrence of major CVD events.


Despite showing an impressive decrease in cardiovascular risk (45%) caution has to be taken. The AASK study in African-American patients showed that nocturnal medications taken resulted in no significant difference in blood pressures compared with daytime dosing. Moreover, people who took their medications at night, rather than in the morning, had greater declines in their mean systolic and diastolic pressures while asleep. Therefore, the nighttime regimen needs to be replicated in other populations before this strategy is widely adopted.

As per the authors, the major limitation of the Hygia Chronotherapy Trial is that its findings require validation and extrapolation to other ethnic groups. In addition, the trial did not assign participants to specific hypertension medication classes or specific list of medications within each class; rather, treatment was chosen by each participating clinician respecting current clinical practice. Nonetheless, differences in prescription rates among the different medication classes reflect current therapeutic preferences in the primary care setting, which in turn was one of the major advantages of the trial.