Could blood pressure tablets be more effective if taken at bedtime?

Several media sources reported that blood pressure tablets work better if taken at bedtime, reducing the risk of a heart attack and early death.

This follows a large trial carried out across general practices in northern Spain. It included around 20,000 adults (aged 60 on average) with high blood pressure.

Half the people were told to take their blood pressure tablets at bedtime, and the other half upon waking. They were followed up for an average of 6 years, during which time around 1 in 10 experienced a heart attack, heart failure or stroke, or died from cardiovascular disease.

The study found that people who took their blood pressure tablets at bedtime has significantly lower nighttime blood pressure and were 45% less likely to have any one of these outcomes.

The trial lends support to past research with similar findings. However, the trial only looked at Spanish people of a white ethnic background. It also did not look at the effect of timing on specific blood pressure tablets. Therefore, as the researchers say, further study is needed before we see if the advice on how to take blood pressure medicines should change.

Unless you're taking diuretics (water tablets), which could mean you have to get up a lot in the night to pee, there should be no negative effects from taking them at night. But it's probably worth speaking to a GP first before making any changes to how you take your medicines, particularly if you're taking a few different medicines.

Read more about treatment for high blood pressure.

Where did the story come from?

This study was done by researchers from the University of Vigo and several other institutions in Spain. The project received funding support from the Spanish government and multiple other organisations.

The study was published in the peer-reviewed European Heart Journal and is openly available to access online.

The UK's media coverage of the study was broadly accurate.

What kind of research was this?

This was a randomised controlled trial aiming to see whether it is better to take blood pressure tablets at bedtime or in the morning. A randomised trial is the best way of looking at the effectiveness of a treatment because randomisation should balance any differences in patient characteristics, such as health and lifestyle, which could influence the result.

One slight limitation is that the trial was open-label (not blinded) meaning patients and researchers were aware of when they took their tablets.

An ideal design may have been to give all patients tablets morning and night, 1 set being the medicine and the other a matching placebo (dummy tablets). However, with the length of trial this would have been very difficult. There could also be risk of mistakes (for example, patients taking 2 sets of placebo tablets a day and none of their medicine).

What did the research involve?

The trial was carried out between 2008 and 2018 across 40 general practices in northern Spain. It included adults who were diagnosed with high blood pressure (hypertension) according to standard criteria and prescribed 1 or more blood pressure medicines.

They recruited a total of 19,084 patients (average 60 years, 56% male) who were told to take their medicines at bedtime or in the morning. Around a quarter of all recruited patients had type 2 diabetes, 43% were obese, 15% were smokers and 10% had already had a past cardiovascular event, such as a heart attack. Patients were taking various types of blood pressure medicine.

Patients were followed up with clinic assessments at least once a year, which included blood tests and wearing a blood pressure monitor for 48 hours (ambulatory blood pressure monitoring). The main outcome of interest was patients who experienced either 1 or more:

• heart attack
• stroke
• a procedure to open the heart arteries (like stent insertion)
• heart failure
• death from cardiovascular disease

They adjusted their analyses for patient age, gender, cholesterol, starting blood pressure, smoking, diabetes and kidney disease.

What were the basic results?

During an average follow-up of 6 years, 1,752 adults (9%) experienced any of the main cardiovascular outcomes.

Patients who took their blood pressure tablets at bedtime had 45% lower risk of any of these events (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50 to 0.61). The researchers also found similar risk reductions when looking at each of the individual outcomes, such as heart attack or stroke.

Results from the 48-hour blood pressure monitoring showed that patients taking their tablets at bedtime had lower blood pressure during the night. There was no difference in daytime blood pressure between the 2.

There was no difference between groups in any side effects from treatment. There was also no difference in how many patients did not take the tablets they were supposed to, or at the time they were supposed to.

How did the researchers interpret the results?

The researchers conclude that taking blood pressure medicines at bedtime results in improved blood pressure control "and, most importantly, markedly diminished occurrence of major cardiovascular disease events".

Conclusion

This is valuable trial investigating the best time to take blood pressure medicines. It has particular strengths of a very large sample size and long duration of follow-up, which is fairly rare for a randomised trial.

It finds that taking medicines at bedtime lowers blood pressure during the night and reduces risk of heart attacks and other cardiovascular outcomes. They found this difference not only when looking at all events combined, but each of them individually. This suggests that the timing of taking medicines can make a real difference. This lends support to previous trials that have had similar findings.

Currently the various blood pressure medicines do not have strict prescribing information on when during the day they need to be taken, with the exception that diuretics (water tablets) are often taken in the morning to prevent people needing to pee frequently during the night.

Despite the positive findings, there are some limitations to the trial. These include that the researchers could not analyse the effect of timing for specific blood pressure medicines. Also the trial was conducted in a predominantly Spanish, exclusively white ethnic population who may not be representative of other populations.

The researchers themselves acknowledge that the results of their trial now need to be validated in other study populations. Further conclusive findings may in future lead to changes in how blood pressure medicines are prescribed.