Key messages
— There may be little to no difference in death for any reason between taking blood pressure-lowering medicines in the morning or evening, but we have no confidence in the results. The difference in unwanted effects was not known.
— Taking blood pressure-lowering medicines in the evening may give slightly better blood pressure control than giving them in the morning for change in blood pressure over a 24-hour period, but we have no confidence in the results.
What is high blood pressure?
High blood pressure (hypertension) is a condition where the pressure inside your arteries is 130 mmHg or greater when your heart is contracting or 80 mmHg or greater when your heart is relaxed, or both of these. The cause of high blood pressure may be unclear or due to some diseases such as kidney disease. People with high blood pressure do not usually have symptoms, but they are at risk for heart attack, stroke and kidney disease.
How is high blood pressure treated?
There are a few ways to help reduce your high blood pressure.
— Take blood pressure-lowering medicines.
— Lose weight (if you are overweight).
— Exercise for at least 30 minutes a day on most days of the week.
— Choose a diet low in salt and fat, and rich in fruits and vegetables.
— Drink less alcohol (if you drink more than two alcoholic drinks per day).
What did we want to find out?
We wanted to find out if taking blood pressure-lowering medicines in the evening gave better results than taking them in the morning to improve death, unwanted effects on the heart and blood vessels, unwanted outcomes overall and blood pressure levels.
What did we do?
We searched for studies that compared taking blood pressure-lowering medicines in the evening with taking them in the morning in people with high blood pressure of unknown cause. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 25 studies including 3016 people with high blood pressure of unknown cause that reported results after three to 26 weeks of treatment with blood pressure-lowering medicines.
Main results
There may be little to no difference in death from all causes and unwanted outcomes overall, but the evidence was very uncertain. Taking blood pressure-lowering medicines in the evening may give slightly better blood pressure control than giving them in the morning for change in blood pressure over a 24-hour period, but we have no confidence in the results. No studies reported unwanted effects on the heart and blood vessels.
What are the limitations of the evidence?
A few factors reduced our confidence in the evidence. The evidence did not cover many black and Asian people, people with more risks of unwanted outcomes, people taking more than one type of blood pressure-lowering medicine, people with high blood pressure caused by certain diseases and shift workers. In addition, study durations were less than six months. There were too few studies to be certain about the results of our outcomes. It is possible that the people in the studies were aware of which treatment they were getting, important data may have been lost in the studies, and not all the studies provided data about everything that we were interested in. Finally, results were very inconsistent across the different studies.
Our lack of confidence in the results means that further research could change the results in this review.
How up to date is this evidence?
This review updates our previous review. The evidence is up to date to June 2022.
Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure.
The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.
Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011.
To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension.
We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions.
We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension.
Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis.
We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported.
The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and β-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials.
No RCTs reported on cardiovascular mortality and cardiovascular morbidity.
There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI −0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI −0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD −0.02, 95% CI −0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD −0.01, 95% CI −0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain.