Treatment of hypertension with chronotherapy: is it time of drug administration?

OBJECTIVE: To review evidence for dosing antihypertensives at bedtime and possible cardiovascular risk reduction.

DATA SOURCES: A PubMed, EMBASE, and Cochrane Controlled Trials database literature search (1990-September 2014) limited to human subjects was performed using the search terms hypertension, chronotherapy, ambulatory blood pressure, morning administration, evening administration, and antihypertensives. Additional references were identified from literature citations.

STUDY SELECTION: All prospective studies assessing cardiovascular outcomes or comparing morning to evening administration of antihypertensives were selected.

DATA SYNTHESIS: Compared with morning administration, dosing one or more antihypertensive medications at bedtime helps induce a normal circadian blood pressure pattern and reduces the risk of cardiovascular disease morbidity and mortality in individuals with hypertension. Similar results have been reported in high-risk individuals with diabetes, chronic kidney disease, and resistant hypertension. A lack of diversity among studied populations and reliance on subgroup analyses are among the limitations of these data. All antihypertensive medications have not been studied in chronotherapy and do not uniformly achieve desired results. The most substantial evidence exists for medications affecting the renin-angiotensin-aldosterone system.

CONCLUSIONS: Despite growing evidence and promise as a cost-effective strategy for reducing cardiovascular risk, chronotherapy is not uniformly recommended in the treatment of hypertension. Careful selection of patients and antihypertensives for chronotherapy is required. Further investigation is needed to evaluate the definitive impact of chronotherapy on cardiovascular outcomes.