What time of day should people take blood pressure medication?
The clinical question
Our blood pressure naturally follows a daily cycle – falling when we sleep at night and rising in the morning. But when someone has high blood pressure, they might not experience a ‘dip’ in their blood pressure during the night. Previous research has suggested that people who don’t have a normal pattern of blood pressure variation between the day and night may be at higher risk of a cardiovascular event, such as experiencing a heart attack or stroke, even if their blood pressure seems to be well-controlled with medication.
This led to the idea that taking blood pressure tablets at night, rather than in the morning, could help to restore a natural blood pressure rhythm and reduce the risk of cardiovascular events. A few research studies had already looked into this, with some suggesting that blood pressure medication might be more effective if taken at night - but more conclusive evidence was needed. Led by Professor Tom MacDonald at the University of Dundee, the BHF-funded Treatment In the Morning versus Evening (TIME) trial aimed to definitively test whether the time of day blood pressure medication is taken impacts how well it works to prevent cardiovascular events.
What did the study involve?
People were eligible to take part in the TIME trial if they had been diagnosed with high blood pressure and were taking at least one blood pressure-lowering medication. The trial was innovative in that enrolment and all the trial procedures didn’t require any in-person research visits, allowing a large number of people to be recruited in a cost-effective way.
Participants were invited to register on the study website via their GP surgery, hospital, or social media. Between 2011 and 2018, 21,104 participants were enrolled in the trial and were randomly assigned, by email, to either:
- Take their blood pressure tablets in the morning (between 6am and 10am).
- Take their blood pressure tablets in the evening (between 8pm and midnight).
Participants were asked to stick to their assigned dosing schedule for the duration of the study, and were followed up for an average of 5 years after being enrolled. This was done by sending regular online questionnaires to participants and tracking their electronic health records to find out whether:
- They were hospitalised with a heart attack, stroke or heart failure.
- They died during follow up, particularly looking at whether it was due to a cause linked to the heart or blood vessels.
- They were sticking to their assigned dosing schedule.
- They experienced any side effects that might be linked to taking blood pressure lowering medication, such as falls or feeling faint.
Participants who already owned a home blood pressure monitor were also asked to submit their morning and evening blood pressure readings to the online study portal every 3 months.
What did the study show?
- The trial showed that blood pressure medication was equally effective at helping to prevent cardiovascular complications whether it was taken in the morning or evening. There was no difference in the number of people who had a heart attack, stroke or died between the two groups - 390 in the ‘morning’ group compared to 362 in the ‘evening’ group.
- About 70% of participants kept to their assigned dosing schedule throughout the trial.
- People in the ‘evening’ group were slightly less likely to report experiencing a fall or symptoms such as feeling faint, but were more likely to report needing to visit the toilet excessively.
Why is the study important?
An estimated one billion people worldwide have high blood pressure, and it’s the leading modifiable risk factor for developing cardiovascular disease. In the UK, around 28% of adults have high blood pressure, and around 50% of heart attacks and strokes are linked to having it.
Blood pressure lowering medications are among the most widely prescribed drugs, with between seven and nine million people in the UK taking them. But many people do not take them as prescribed – for example, people can be put off if they experience side effects like feeling faint after taking their tablets in the morning. The results of this study mean that the many people taking these medications can be confident that they are helping to protect their health, whatever time of day works best for them to take their tablets.
Summarising the trial’s finding at the 2022 European Society of Cardiology Conference, Professor MacDonald said: “TIME was one of the largest cardiovascular studies ever conducted and provides a definitive answer on the question of whether blood pressure lowering medications should be taken in the morning or evening. The trial clearly found that heart attack, stroke and vascular death occurred to a similar degree regardless of the time of administration.
Professor McDonald also spoke about the results of TIME at a BHF Live & Ticking event in May 2022 - watch below.
The participant voice
Brian has had high blood pressure for many years, and tried lots of different tablets and combinations before finding a specific dose of a combination tablet (including the angiotensin receptor blocker telmisartan and the diuretic hydrochlorothiazide) that worked best for him. Prior to taking part in the TIME trial, he had been been taking this medication in the morning. He found out about the trial through his GP, where he volunteers as chairman of their Patient Participation Group.
He said: "I can't remember exactly how I got involved in the trial, but I've always said to the practice manager, if there's anything going on I can help with, sign me up! I also didn't really think of taking part in this study as a 'trial', as I didn’t need to attend any visits or go and have any tests done as part of it, and I take regular blood pressure readings to send to my GP anyway."
Having been assigned to evening dosing, Brian completed the trial surveys and submitted blood pressure readings to the trial team about three times a year between June 2016 and June 2020. He didn't have any issues with switching his dosing time, and since the study ended he's continued to take the medication in the evening.
Study details
“Treatment In the Morning versus Evening (TIME study).”
Award reference: CS/14/1/30659
Principal investigator: Professor Thomas MacDonald
Trial registration number: ISRCTN18157641
Publication details
Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. Lancet. 2022;400(10361):1417-1425.