A 54-year-old White woman presents to your office with new-onset hypertension. As you are discussing options for treatment, she mentions she would prefer once-daily dosing to help her remember to take her medication. She also wants to know what the best time of day is to take her medication to reduce her risk of cardiovascular disease (CVD). What do you advise?
The burden of hypertension is significant and growing in the United States. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines reported that more than 108 million people were affected in 2015-2016—up from 87 million in 1999-2000.2 Yet control of hypertension is improving among those receiving antihypertension pharmacotherapy. As reported in the ACC/AHA guidelines, data from the 2016 National Health and Nutrition Examination Survey (NHANES) indicate an increase of controlled hypertension among those receiving treatment from 25.6% (1999-2000) to 43.5% (2015-2016).2
Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximize therapeutic effectiveness and/or minimize adverse effects. It is not a new concept as it applies to hypertension. Circadian rhythm–dependent mechanisms influence the natural rise and fall of blood pressure (BP).1 The renin-angiotensin-aldosterone system, known to be most active at night, is a target mechanism for BP control.1 Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are more effective (alone or in combination with other agents) at reducing BP during sleep and wakefulness when they are taken at night.3,4 Additional prospective clinical trials and systematic reviews have documented improved BP during sleep and on 24-hour ambulatory monitoring when antihypertensives are taken at bedtime.3-5
However, there have been few long-term studies assessing the effects of bedtime administration of antihypertensive medication on CVD risk reduction with patient-oriented outcomes.6,7 Additionally, no studies have evaluated morning vs bedtime administration of antihypertensive medication for CVD risk reduction in a primary care setting. The 2019 ACC/AHA guideline on the primary prevention of CVD offers no recommendation regarding when to take antihypertensive medication.8 Timing of medication administration also is not addressed in the NHANES study of hypertension awareness, treatment, and control in US adults.9
This study sought to determine in a primary care setting whether taking antihypertensives at bedtime, as opposed to upon waking, more effectively reduces CVD risk.
PM vs AM antihypertensive dosing reduces CV events
This prospective, randomized, open-label, blinded endpoint trial of antihypertensive medication administration timing was part of a large, multicenter Spanish study investigating ambulatory BP monitoring (ABPM) as a routine diagnostic tool.
Study participants were randomly assigned in a 1:1 ratio to 2 treatment arms; participants either took all of their BP medications in the morning upon waking (n = 9532) or right before bedtime (n = 9552). The study was conducted in a primary care clinical setting. It included adult participants (age ≥ 18 years) with hypertension (defined as having at least 1 of the following benchmarks: awake systolic BP [SBP] mean ≥ 135 mm Hg, awake diastolic BP (DBP) mean ≥ 85 mm Hg, asleep SBP mean ≥ 120 mm Hg, asleep DBP mean ≥ 70 mm Hg as corroborated by 48-hour ABPM) who were taking at least 1 antihypertensive medication.
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