Volume 1 Issue 16
August 2016  
Context and Study Objective
Anti-hypertensives are generally prescribed for morning administration. Given the benefits of  24 hour blood pressure (BP) control, Hermida explored the impact of adjusting the time of medication administration ("chronotherapy") on ambulatory BP control. Dipping, an additional outcome, will not be addressed.  

Design, Setting, and Participants
A randomized, open-label, blinded end point trial (investigators responsible for end point analysis were unaware of group assignment) was conducted among those with resistant hypertension. Individuals with cardiovascular (CV) disease, diabetes, or kidney disease were excluded. Baseline ambulatory readings were collected on patients while on a morning 3 drug regimen of a diuretic, ACE/ARB, and a third agent consisting of amlodipine/nifedipine (CCB) or doxazosin. Patients were then randomized to ongoing morning administration of a diuretic and RAAS blocker but with the alternate 3rd agent (i.e., a CCB for those previously receiving an alpha antagonist) being given in the morning or evening. The resultant BP readings were then compared to baseline pressures. 
-250 participants had a mean age of 60. Average clinic BP was 158/88 mm Hg, 24hr mean BP 137/79 mm Hg, and  Cr 1.0 mg/dL. At study onset, equal numbers of patients were on doxazosin or a CCB.
-Regardless of the dosing regimen, office BP was identical to pre-trial readings.
-Top Figure: By ambulatory monitoring, there was no difference among those randomized to morning dosing of the alternate 3rd agent.
-Bottom Figure: Those randomized to night time dosing experienced a marked decline in BP, particularly during the overnight hours. 
Clinical Perspective

-My own experience suggests chronotherapy to be a valuable tool allowing for improved BP control in those with/without resistant hypertension. It can avoid the need for an additional agent and allows for enhanced blood pressure control in the early morning hours  when the rate of CV events is highest.
-Office pressures were identical between groups; this is not unusual given visits occurred during daytime hours, a period during which the anti-hypertensive efficacy of even shorter acting agents remain in effect. Conversely, clinic readings fail to capture BP elevations during  the overnight hours when medications that lack 24 hour coverage begin to wane.  
-Limitations: The study only included those with resistant hypertension who were free of  CV and kidney disease. It is unclear why the 3rd agent was replaced rather than simply changing the timing of its administration.  While specific diuretic and CCB selection could impact BP control, the randomized nature of the trial eliminated this possible confounder. 
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