Researchers found that bedtime dosing of olmesartan-amlodipine improved nocturnal blood pressure control without increasing adverse events in patients with hypertension.

Bedtime dosing of olmesartan-amlodipine improved nocturnal blood pressure control without increasing adverse events in adults with hypertension, according to results from a large randomized clinical trial conducted in China.

Patients who took their antihypertensive medication at bedtime experienced significantly greater reductions in nighttime systolic blood pressure (SBP) compared with those who dosed in the morning. Researchers conducted the multicenter OMAN randomized clinical trial to assess whether bedtime administration of a fixed-dose combination of olmesartan, 20 mg, and amlodipine, 5 mg, improved nocturnal BP control and circadian rhythm compared with morning dosing.

Study Design and Outcomes

The trial enrolled 720 adults with essential hypertension across 15 hospitals in China from June 2022 to April 2024. Participants were either untreated or off antihypertensive therapy for at least two weeks. They were randomized to take the medication once daily in the morning (6:00–10:00 AM; n = 352) or at bedtime (6:00–10:00 PM; n = 368). Dosages were titrated at weeks 4 and 8 based on ambulatory and office BP readings.

At 12 weeks, the bedtime group saw a greater mean reduction in nighttime SBP (−25.3 mm Hg) than the morning group (−22.3 mm Hg), with a statistically significant between-group difference of −3.0 mm Hg (P = .004). Bedtime dosing also yielded greater reductions in nighttime diastolic BP (−1.4 mm Hg; P = .04), morning SBP (−3.1 mm Hg), and morning DBP (−2.7 mm Hg).

Patients in the bedtime group achieved higher nocturnal SBP control rates (79.0% vs 69.8%; P = .01) and greater office BP control (88.7% vs 82.2%; P = .02). No differences were observed between groups in adverse event rates, incidence of nocturnal hypotension, or adherence to assigned dosing times (5.4% vs 4.5%; P = .58).

Subgroup and Safety Findings

Subgroup analyses suggested the benefits of bedtime dosing were more pronounced in men, individuals over age 65, those with BMI over 24, nonsmokers, nondrinkers, and participants with higher baseline SBP (155 mm Hg or greater). Importantly, the study found no increased risk of adverse events or nocturnal hypotension, reinforcing the safety of bedtime dosing even in these populations.

Limitations and Considerations

While the findings support bedtime administration as a potential strategy to improve nocturnal BP control and circadian rhythm, several limitations temper the generalizability:

• The study population consisted exclusively of Chinese adults without established cardiovascular disease.

• The duration was limited to 12 weeks, and long-term cardiovascular outcomes were not assessed.

• Dosing-time adherence was self-reported, which may introduce bias.

• Results may not extend to other antihypertensive drug combinations.

Clinical Implications and Next Steps

The results contribute to the growing body of evidence supporting antihypertensive chronotherapy. A 3-mm Hg difference in nighttime SBP, as observed here, may translate into meaningful cardiovascular risk reductions over time. However, the authors call for longer-term trials in more diverse populations to determine whether bedtime dosing improves clinical outcomes such as myocardial infarction or stroke incidence.

Disclosures

The study authors reported no conflicts of interest. Funding was provided by Nanjing Chia Tai Tianqing Pharmaceutical Co Ltd and regional science foundations. The funders had no role in study design, data analysis, or publication decisions.

Source: JAMA Network Open