When to take blood pressure pills - in the morning or in the evening? Research answers

Arterial hypertension remains the leading modifiable risk factor for mortality worldwide, and nighttime blood pressure and the pattern of its “fall” during sleep are more often more closely associated with heart attack, stroke, and mortality than daytime and office measurements. This makes monitoring of nighttime pressure an independent therapeutic goal: in a significant proportion of patients, even those receiving treatment, it is the nighttime component that remains undercontrolled.

A logical clinical question was chronomedical optimization: can simply shifting the timing of antihypertensive drug administration to the evening improve the night-time blood pressure profile without losing daytime control? The evidence base for “evening” administration remained heterogeneous: some studies showed an advantage for the 24-hour profile, while others - especially in vulnerable groups - found no benefit for “hard” outcomes, which required well-designed randomized trials with objective ambulatory monitoring (ABPM).

A multicenter randomized trial published in JAMA Network Open addresses this gap: it directly compares morning versus evening dosing of a fixed-dose combination of antihypertensive agents in adults with hypertension, assessing the effects on nighttime blood pressure, circadian rhythm, and ABPM control. This design separates the question of “when to take” from “what and how much to take,” and makes the primary endpoint nighttime blood pressure—a risk component that is often “eluded” by standard morning treatment.

The results of this RCT have already attracted interest from clinicians and the media, as they point to potential benefits of evening dosing for reducing nighttime BP and improving circadian organization without compromising daytime BP or increasing the risk of nocturnal hypotension. This raises practical questions about who should benefit from evening dosing, when, and how these data fit into existing hypertension management guidelines.

In 15 clinics in China, 720 people with hypertension were prescribed the same combination pill (olmesartan 20 mg + amlodipine 5 mg) and randomly asked to take it either in the morning (6-10) or before bedtime (18-22) for 12 weeks. Evening administration lowered nighttime pressure more strongly and restored circadian rhythm better, without worsening daytime and 24-hour indicators and without increasing nighttime hypotension. The difference in nighttime systolic pressure was about 3 mm Hg in favor of the "evening".

Background of the study

Control of night-time (and not just daytime or “office”) blood pressure has long been considered the key to reducing cardiovascular risk. According to large cohorts and meta-analyses, it is night-time pressure and the nature of “nighttime dipping” that are more strongly associated with outcomes – heart attack, stroke, heart failure and mortality – than daytime and office measurements. This applies to both the general population and patients with treated hypertension, where “insufficient” pressure drop at night is an independent marker of poor prognosis.

Hence the interest in chronomedicine: can the night-time blood pressure profile be improved by “shifting” the timing of antihypertensive drug administration? However, the evidence base here has until recently remained patchy. A number of studies and reviews have emphasized the benefits of evening administration for controlling the 24-hour profile, while other studies, particularly those focused on “hard” clinical outcomes in vulnerable groups (e.g., elderly and frail patients), have found no effect on mortality or major cardiovascular events. As a result, professional guidelines have long maintained a cautious stance, calling for individual risk and patient convenience to be taken into account.

In this context, randomized trials that focus on objective outpatient measurements (ABPM) and clearly compare morning and evening administration of the same treatment regimens have become particularly relevant. The study published in JAMA Network Open was designed to answer precisely this practical question: does shifting the administration of a fixed-dose combination (olmesartan/amlodipine) to the night affect nighttime blood pressure and circadian rhythm compared to morning administration, with the total dose and duration of treatment unchanged.

An important methodological detail of this RCT is the registration in the Chinese clinical trials registry and the use of a standardized ABPM to estimate both mean nighttime values and the proportion of patients achieving target levels at night. This design allows us to separate the question of “when to take” from the question of “what and how much to take” and thus provide clinicians with a practical guideline specifically for the correction of nocturnal hypertension, the risk component that often remains undercontrolled with the usual morning drug intake.

Why argue about the time of the appointment at all?

Nighttime blood pressure is a powerful predictor of stroke, heart attack, and target organ damage. In many treated patients, it is the night that remains the "weak point": there is no normal "dipping" (a drop in blood pressure by ≥10% relative to daytime), and the morning "rise" is pronounced. The idea of chronotherapy is simple: adjust the peak of the drug's action to the night and early morning. But the data were contradictory: some studies showed the benefit of evening intake, others did not. OMAN just adds accurate figures based on daily monitoring.

How exactly was the study conducted?

• Participants: 720 adults with mild-moderate hypertension (mean age 55.5 years; 57% men). Either no therapy at all before or a 2-week washout.
• What was given: a fixed combination of olmesartan/amlodipine 20/5 mg once a day. At the 4th and 8th week, the dose could be titrated (up to 1.5-2 tablets) based on the results of daily monitoring (ABPM) and office pressure.
• The main goal: how much more will the night systolic BP fall after 12 weeks.
• Additionally: night diastolic, morning values, proportion of "dippers", pressure load, proportion of those achieving target values for ABPM and in the office, safety (including episodes of nocturnal hypotension).

What happened?

• Nighttime SBP fell more significantly with evening administration: -25.3 versus -22.3 mmHg.
  Difference between groups: -3.0 mmHg (significant).
• Nighttime DBP: additional reduction of -1.4 mmHg with evening regimen.
• Night-time SBP control: 79.0% achieved the target with evening administration versus 69.8% in the morning.
• The circadian rhythm has improved: there are fewer people without a nighttime dip (“non-dippers”) and lower morning readings.
• During the day and over 24 hours, the effectiveness did not drop.
• Safety: Nocturnal hypotension no longer occurs more frequently; adverse event profile is comparable.
• Doses: It is interesting that the morning group often required greater titration (by the 8th week more at a dose of 2 tablets/day), but the effect was still inferior to the evening group.

Is 3 mm a lot? For the population, yes: a decrease in office SBP by 2-5 mm Hg is associated on average with a ~7-10% lower risk of cardiovascular events. OMAN is talking about night pressure (even more "prognostic"), so such an increase may make sense. The outcome (stroke/heart attack) was not assessed - a longer and larger project is needed for this.

Who was helped most noticeably by the “evening”

In the subgroups, the gain was greater for:

• men,
• people over 65,
• with BMI ≥24,
• non-smoking,
• with high initial office SBP (≥155).

The subgroups are guidelines, not hard and fast rules, but the trend is clear.

Why it worked (plausible mechanisms)

• The renin-angiotensin-aldosterone system is more active at night: taking olmesartan before bedtime more accurately “hits” this period.
• Amlodipine peaks at 6-12 hours and has a long half-life; evening dosing produces greater effects at night and at dawn.
• It's not just "more pills in the evening" - on the contrary, in the morning I had to increase the dose more often.

How does this relate to previous controversies?

• High-profile works (for example, Hygia) demonstrated the enormous benefits of the “evening”, but raised questions about the methods and scale of the effect.
• The large UK TIME study found no difference in major morning vs evening outcomes, but not everyone had baseline ABPM and most were already on therapy.
• OMAN strengthens the arguments in favor of the evening regimen based on night-time BP: daily monitoring for everyone before and after, fixed combination, clear intake windows, titration according to ABPM and office.

Restrictions

• 12 weeks is about blood pressure, not about heart attacks/strokes. Long initial studies are needed.
• Participants were Chinese patients without overt CVD: transferability to other populations/comorbidities needs to be confirmed.
• Self-reporting of the time of admission - inaccuracies are possible.
• The results apply to the olmesartan+amlodipine combination; for other classes/combinations the time effect may differ.

What does this mean for the patient and the doctor?

• If you/your patient have a poor night profile (according to ABPM): “non-dipping”, high night/morning rise, - transferring a fixed combination such as olmesartan/amlodipine to the evening may provide an addition to night control without losing daytime efficacy.
• Do not change the time of administration arbitrarily. Time is the same part of the scheme as the dose: discuss with your doctor, especially if you have CKD, orthostatic hypotension, sleep disorders, taking diuretics/alpha-blockers, risk of falls.
• ABPM is the key. It is better to make a decision about chronotherapy based on daily monitoring data, and not just on office numbers.
• The focus on simple regimens (1 tablet once a day, fixed combinations) increases adherence and makes it easier to transfer to the evening.

A practical checklist for your visit

1. Is there ABPM data (before/after)?
2. Night profile: dipping ≥10%? Morning surge?
3. Drugs: Is there a long-acting ARB/AC combination?
4. Risks of hypotension at night (falls, CKD, old age, weakness during the day)?
5. If we decide to transfer - one parameter at a time (time → assessment → dose if necessary).

Conclusion

In OMAN, evening dosing of olmesartan/amlodipine resulted in better nocturnal BP and circadian rhythm control, without increasing hypotension or worsening daytime control. This is not a “magic bullet,” but it is further neat evidence that timing of dosing matters for some regimens – especially when the No. 1 goal is nocturnal BP.

Source: Ye R, Yang X, Zhang X, et al. Morning vs Bedtime Dosing and Nocturnal Blood Pressure Reduction in Patients With Hypertension: The OMAN Randomized Clinical Trial. JAMA Network Open. 2025;8(7):e2519354. doi:10.1001/jamanetworkopen.2025.19354.