Current hypertension management guidelines do not specify a preferred time for treatment with blood pressure (BP)-lowering medications, but the most common recommendation by clinicians is morning treatment. However, new findings from the Hygia Chronotherapy trial suggest that taking antihypertensive medications at bedtime is associated with better BP control and a 45% reduction in the risk of cardiovascular disease (CVD) compared with taking the medication in the morning upon waking up.

This multicentre, controlled, prospective trial was conducted in the primary care setting and included 19,084 patients with hypertension (10,614 men and 8,470 women) who had a prescription of more than one BP-lowering drug. Patients were randomly assigned to take their entire daily dose of antihypertensive medications either at bedtime or upon waking up. Ambulatory BP (ABP) monitoring for 48 h was performed at baseline and at every scheduled clinic visit. After a median of 6.3 years, the bedtime-treatment group had improved ABP control, with lower asleep systolic BP (SBP) and greater sleep-time relative SBP decline (that is, BP dipping), compared with the morning-treatment group. Furthermore, the primary CVD outcome (a composite of CVD death, myocardial infarction, coronary revascularization, heart failure or stroke) occurred in fewer patients in the bedtime-treatment group than in the morning-treatment group (HR 0.55, 95% CI 0.50–0.61, P < 0.001) after adjustment for factors including age, sex, asleep SBP mean, sleep-time relative SBP decline and previous CVD. Analysis of the individual primary outcome components showed similar results.

In summary, the time of treatment seems to be important for BP control and protection against CVD. However, the mechanism for the benefit of bedtime dosing is unclear. Ongoing, large-scale trials assessing antihypertensive treatment timing might provide further insights into the role of circadian treatment patterns.