Blood pressure has a circadian variation. Patients whose blood pressure lowers during the night tend to experience fewer cardiovascular events compared to those whose blood pressure barely dips. This can be detected by 24-hour blood pressure monitoring. A hypothesis follows that nocturnal dosing of antihypertensives may be more cardioprotective than morning dosing.21
An early single-centre study of 2156 patients reported a reduction in cardiovascular events with nocturnal dosing of one or more antihypertensive drugs versus taking all antihypertensives in the morning.22 However this result was subject to criticism. A larger study in around 18,000 hypertensive patients also concluded that bedtime ingestion of one or more antihypertensives was associated with a significantly lower risk of cardiovascular morbidity and mortality.23 The Treatment in Morning versus Evening (TIME) trial randomised 21,000 patients to take all their antihypertensive drugs either in the morning or evening. Its results are expected in late 2019.12
Whether the combined outcomes from these large chronotherapy studies will influence the timing of doses in international guidelines remains to be seen. In the interim, antihypertensive drugs may be taken consistently at a time of day that maximises adherence.
Diuretics are given in the morning, as diuresis at night may interfere with sleep and increases the risk of falls in older patients. If patients require twice-daily dosing, the diuretic potency determines the appropriate timing of the second dose. For potent loop diuretics, give the second dose at midday. For hydrochlorothiazide or amiloride, give the second dose before 6 pm.