Chronotherapy of hypertension with combination treatment.

In the last decade, a number of clinical studies identified an additional improvement of blood pressure control if the single drug treatment is time-targeted in hypertensive individuals. On the other hand, only a few of them investigated whether any different antihypertensive effects with combination therapy can be confirmed between morning and evening dosing. This article reviews those studies employed various combinations of antihypertensive agents including calcium channel blocker with angiotensin-receptor blocker, calcium channel blocker with diuretic, angiotensin-receptor blocker with diuretic, angiotensin-receptor blocker with angiotensin-converting enzyme inhibitor and angiotensin-converting enzyme inhibitor with diuretic. Interestingly, the majority of studies confirmed that evening dosing is more effective in reducing asleep and/or mean systolic and/or diastolic blood pressure, one study found no difference and one study suggested that morning dosing could be more effective. Three studies showed a positive shift from non-dipping to dipping pattern with evening dosing and an opposite effect was found with morning dosing. Importantly, while the data strongly suggest that efficacy can be improved with evening dosing when drug combination is used, no thought was given to safety comparison. Thus, the complex benefit-risk ratio comparison between morning and evening dosing of blood pressure reducing drug combinations remains to be elucidated.