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Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial
Ramón C Hermida1, Juan J Crespo1,2, Manuel Domínguez-Sardiña2
1Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC), University of Vigo, E.I. Telecomunicación, Campus Universitario, Vigo 36310, Spain.
Insights
Taking hypertension medication at bedtime significantly reduces cardiovascular disease risk compared to taking it upon waking. This bedtime regimen improves blood pressure control and lowers major adverse cardiovascular events in hypertensive patients.
Area of Science:
- Cardiology
- Chronobiology
- Hypertension Management
Background:
- Hypertension is a major risk factor for cardiovascular disease (CVD).
- Current hypertension treatment guidelines often recommend morning medication intake.
- The optimal timing for antihypertensive medication to maximize cardiovascular risk reduction is not fully established.
Purpose of the Study:
- To investigate whether taking antihypertensive medications at bedtime, compared to upon awakening, leads to better cardiovascular disease risk reduction.
- To assess the impact of bedtime versus morning dosing on ambulatory blood pressure (ABP) control and major CVD outcomes.
Main Methods:
- A multicentre, controlled, prospective endpoint trial involving 19,084 hypertensive patients.
- Patients were randomized to ingest their daily antihypertensive medications entirely at bedtime or upon awakening.
- Ambulatory blood pressure monitoring was conducted at baseline and annually; major CVD outcomes were tracked over a median follow-up of 6.3 years.
Main Results:
- Patients taking medication at bedtime demonstrated a significantly lower adjusted hazard ratio for the primary CVD outcome (0.55; 95% CI 0.50-0.61; P < 0.001).
- Bedtime dosing led to improved ABP control, including a greater decrease in asleep systolic blood pressure and enhanced sleep-time relative blood pressure decline (dipping).
- Significant reductions were observed for all individual CVD outcome components, including CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke.
Conclusions:
- Ingesting antihypertensive medications at bedtime significantly improves blood pressure control, particularly asleep blood pressure and nocturnal dipping.
- Bedtime administration of antihypertensive therapy markedly diminishes the occurrence of major cardiovascular events in hypertensive patients.
- This chronotherapy approach offers a more effective strategy for reducing cardiovascular risk in patients with hypertension.
Aims:
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.
Methods And Results:
In 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)].
Conclusion:
Routine 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 Registration:
ClinicalTrials.gov, number NCT00741585.
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