Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure

Abstract

Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki. Patients were randomized to receive usual therapy either in the morning (6 am –11 am ) or evening (6 pm –11 pm ) for 12 weeks when participants crossed over to the alternative timing for a further 12 weeks. Clinic blood pressures and a 24-hour recording were taken at baseline, 12, and 24 weeks and routine blood tests were taken at baseline. The study had 80% power to detect 3 mm Hg difference in mean 24-hour systolic blood pressure (α=0.05) by time of dosing. A 2-level hierarchical regression model adjusted for center, period, and sequence was used. Of 103 recruited patients (mean age, 62; 44% female), 95 patients (92%) completed all three 24-hour recordings. Mean 24-hour systolic and diastolic blood pressures did not differ between daytime and evening dosing. Similarly, morning and evening dosing had no differential impact on mean daytime (7 am –10 pm ) and nighttime (10 pm –7 am ) blood pressure levels nor on clinic levels. Stratification by age (≤65/≥65 years) or sex did not affect results. In summary, among hypertensive patients with reasonably well-controlled blood pressure, the timing of antihypertensive drug administration (morning or evening) did not affect mean 24-hour or clinic blood pressure levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01669928.

Restoration of nocturnal blood pressure dip and reduction of nocturnal blood pressure with evening anti‐hypertensive medication administration in pediatric kidney transplant recipients: A pilot randomized clinical trial

“…9,22,[51][52][53][54] In contrast, there have been a few smaller-powered studies with various study designs that reported no difference between evening and morning administration of anti-hypertensive medications. 14,55 One such study, the HARMONY trial, transplantation. One study in adults with CKD found that daytime and nighttime BP were predictive of myocardial infarction, stroke, and death.…”

Can We Mend the Broken Clock by Timing Antihypertensive Therapy Sensibly?

“…Compared with baseline, there was no difference in nighttime SBP with 12-week-long dosing of all BP-lowering medications either in the morning or at bedtime. After adjustment for center, carry over, and period effects, nighttime SBP did not differ between the bedtime and the morning dosing regimen (between-group difference: 21.62 mm Hg; 95% CI, 25.38 to 2.15 mm Hg) (8).…”

“…The effect of timing of antihypertensive therapy on ambulatory BP profile was explored in the 2018 Hellenic-Anglo Research into Morning or Night Antihypertensive Drug Delivery (HARMONY) trial (8). This trial enrolled 103 patients with hypertension with clinic BP #150/90 mm Hg under stable therapy for at least 3 months from 2 centers in London and Thessaloniki.…”

“…At this time point, participants were crossed over to the other dosing regimen for another 12-week period. ABPM was repeated at the end of each phase (8). Of the 103 patients with hypertension originally enrolled, 95 participants completed the three prespecified ABPM recordings and were included in the analysis.…”

Once versus twice daily antihypertensive medications for the control of nocturnal blood pressure: a comparative study

“…Despite its many drawbacks, office BP measurement is still considered the golden standard for diagnosing HTN and for determining the threshold of initiation and follow-up of anti-hypertensive medications. Many studies showed that data provided by ambulatory blood pressure (ABPM) as nighttime blood pressure and dipping status are stronger predictors of cardiovascular outcome than office BP [3]. Because of its cost and lack of availability in many health centers, ABPM cannot yet replace the office BP measurements, so it is reserved to situations where office BP alone cannot explain the clinical circumstances of the patient.…”