Bedtime dosing of antihypertensive medications may provide improved outcomes over morning dosing

1. Bedtime dosing of antihypertensive medication provided better control of nocturnal BP and improved the circadian rhythm compared to morning dosing.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Nocturnal blood pressure (BP) is more sensitive in predicting cardiovascular events than office, 24-hour, or daytime BP. Achieving nocturnal BP control may reduce the risk of cardiovascular events and mortality among patients with hypertension. However, managing nocturnal BP is difficult in clinical practice. One potential approach to controlling nocturnal BP is antihypertensive chronotherapy, which involves timing the administration of antihypertensive medication. Some studies have shown that bedtime dosing of antihypertensive drugs may be more beneficial than morning dosing, although findings remain controversial. This study thus compared the effects of morning vs bedtime antihypertensive medication administration on nocturnal BP reduction and circadian rhythm among patients with hypertension. Patients with hypertension aged 18 to 75 years were included and randomized 1:1 to one of two dosing groups: morning (6-10 am) or bedtime (6-10 pm), with follow-up over 12 weeks. The antihypertensive medication administered was olmesartan-amlodipine. Out of the 720 participants included, 352 were in the morning dosing group and 368 were in the bedtime dosing group. At 12 weeks, patients in the bedtime dosing group had greater reductions in nighttime systolic BP and nighttime diastolic BP compared to those in the morning dosing group. Patients in the bedtime dosing group also had a better nocturnal systolic BP control rate and improved circadian rhythm. Overall, this study found that bedtime dosing of antihypertensive medication provided better control of nocturnal BP and improved the circadian rhythm compared to morning dosing. 

Click to read the study in JAMA Network Open

Relevant reading: Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

In-Depth [Randomized clinical trial]: This trial, called “The Effects of Olmesartan/Amlodipine Administered in the Morning or at Night on Nocturnal Blood Pressure Reduction in Chinese Patients With Mild-Moderate Essential Hypertension (OMAN) Trial”, was a prospective, multicenter, randomized, open-label, parallel-group, superiority clinical trial. It was conducted at 15 hospitals in China between June 1, 2022, and April 30, 2024. Patients with hypertension aged 18 to 75 years without prior antihypertensive treatment or who had discontinued antihypertensive agents for 2 weeks were included and randomized 1:1 to one of two dosing groups: morning (6-10 am) or bedtime (6-10 pm). Each patient received 1 tablet of olmesartan-amlodipine (20 mg olmesartan, 5 mg amlodipine) daily as the initial treatment for 4 weeks. Patients were followed up every 4 weeks for 12 weeks, during which the olmesartan-amlodipine dosage was adjusted based on the ambulatory BP monitoring (ABPM) and office BP monitoring (OBPM) values. Controlled BP was defined as 24-hour BP < 130/80 mm Hg, daytime BP < 135/85 mm Hg, nighttime BP < 120/70 mm Hg, and OBPM < 140/90 mm Hg. In total, 720 participants were included in the intention-to-treat analysis (mean [SD] age, 55.5 [10.6] years; 409 men [56.8%]), of which 352 were in the morning dosing group and 368 in the bedtime dosing group. In total, 607 (84.3%) completed the 12-week follow-up and were included in the per-protocol population. The mean (SD) baseline BP values for morning vs bedtime dosing were as follows: 24 hour BP, 148.0 (11.1)/91.4 (9.0) mm Hg vs 147.6 (11.0)/91.6 (9.2) mm Hg; daytime BP, 152.3 (11.0)/94.0 (9.2) mm Hg vs 151.5 (11.6)/94.0 (9.8) mm Hg; nighttime BP, 138.4 (15.1)/85.4 (10.4) mm Hg vs 138.3 (13.0)/85.8 (9.4) mm Hg; office BP: 154.4 (12.1)/94.6 (10.3) mm Hg vs 154.3 (12.5)/95.1 (11.1) mm Hg. Compared with patients in the morning dosing group at 12 weeks, patients in the bedtime dosing group had greater reductions in nighttime systolic BP (between-group difference, −3.0 mm Hg [95% CI, −5.1 to −1.0 mm Hg]), and nighttime diastolic BP (between-group difference, −1.4 mm Hg [95% CI, −2.8 to −0.1 mm Hg]). Patients in the bedtime dosing group also had a better nocturnal systolic BP control rate (79.0% [244 of 309] vs 69.8% [208 of 298]; P = .01) and improved circadian rhythm than those in the morning dosing group. Study results were consistent in the per-protocol population. The mean daytime BP, mean 24-hour BP, and incidence of nocturnal hypotension did not differ between the two dosing groups. Overall, this study found that bedtime dosing of antihypertensive medication provided better control of nocturnal BP and improved the circadian rhythm compared to morning dosing, without reducing the efficacy on mean daytime or 24-hour BP, or increasing the risk of nocturnal hypotension. Future studies should confirm these results in other populations, explore other single-pill combinations and antihypertensive drugs, and examine cardiovascular benefits over a period longer than three months. 

Image: PD

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