Is the blood pressure-lowering effect of beta-blockers with partial agonist activity consistent or variable throughout the day?

Review question

This review explores whether the blood pressure-lowering effect of beta-blockers with partial agonist activity is consistent or variable throughout the day in adults with high blood pressure (upper blood pressure reading of at least 140 mmHg, or lower blood pressure reading of at least 90 mmHg, or both).

Background

High blood pressure, also known as hypertension, is very common in the general population, and if not treated, can increase the risk of stroke and heart disease. In an individual, blood pressure naturally varies throughout the day. It is at its lowest at night, rises before awakening, and then falls progressively during the day. Changes to this pattern of variation have been found to be a risk factor for heart disease, independent of the degree of rise in blood pressure.

Beta-blockers are commonly used in the treatment of high blood pressure. Currently, we do not know whether beta-blockers lower blood pressure to different degrees at different times of the day, and how this differs when compared to other classes of drugs used to treat high blood pressure. This review focused on a particular class of beta-blockers – those with partial agonist activity (molecules that both activate and inhibit its receptor).

Search date

We searched the available scientific literature, and included relevant studies up to June 2020.

Study characteristics

We sought studies that examined the blood pressure-lowering effects of treatment with six beta-blockers with partial agonist activity at different times throughout a 24-hour period, measured by a device that automatically measures blood pressure at regular intervals (ambulatory monitoring).

Key results

We identified seven studies, involving 121 participants, that studied three of the six beta-blockers with partial agonist activity (acebutolol, pindolol, and bopindolol). We found that these beta-blockers lowered blood pressure and heart rate more during the day and evening than at night. Currently, we do not know the benefits and harms of this pattern of blood pressure lowering, such as its impact on reducing stroke and heart disease.

Certainty of the evidence

Only a small number of eligible studies were identified, involving relatively few participants. We judged the majority of studies at high or unclear risk of bias. We judged the overall certainty of the evidence to be very low for all outcomes. Further research is likely to have important impact on the estimate of effect and may change the conclusion.

Authors' conclusions: 

There is insufficient evidence to draw general conclusions about the degree of variation in hourly BP-lowering efficacy of BBPAA over a 24-hour period, in adults with essential hypertension. Very low-certainty evidence showed that BBPAA acebutalol, pindolol, and bopindolol lowered BP more during the day and evening than at night. However, the number of studies and participants included in this review was very small, further limiting the certainty of the evidence. We need further and larger trials, with accurate recording of time of drug intake, and with reporting of standard deviation of BP and HR at each hour.

Read the full abstract...
Background: 

Beta-blockers are commonly used in the treatment of hypertension. We do not know whether the blood pressure (BP) lowering efficacy of beta-blockers varies across the day. This review focuses on the subclass of beta-blockers with partial agonist activity (BBPAA).

Objectives: 

To assess the degree of variation in hourly BP lowering efficacy of BBPAA over a 24-hour period in adults with essential hypertension.

Search strategy: 

The Cochrane Hypertension Information Specialist searched the following databases for relevant studies up to June 2020: the Cochrane Hypertension Specialised Register; CENTRAL; 2020, Issue 5; MEDLINE Ovid; Embase Ovid; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.

Selection criteria: 

We sought to include all randomised and non-randomised trials that assessed the hourly effect of BBPAA by ambulatory monitoring, with a minimum follow-up of three weeks.

Data collection and analysis: 

Two review authors independently selected the included trials and extracted the data. We assessed the certainty of the evidence using the GRADE approach. Outcomes included in the review were end-point hourly systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), measured using a 24-hour ambulatory BP monitoring (ABPM) device.

Main results: 

Fourteen non-randomised baseline controlled trials of BBPAA met our inclusion criteria, but only seven studies, involving 121 participants, reported hourly ambulatory BP data that could be included in the meta-analysis. Beta-blockers studied included acebutalol, pindolol and bopindolol. We judged most studies at high or unclear risk of bias for selection bias, attrition bias, and reporting bias. We judged the overall certainty of the evidence to be very low for all outcomes.

We analysed and presented data by each hour post-dose. Very low-certainty evidence showed that hourly mean reduction in BP and HR visually showed an attenuation over time. Over the 24-hour period, the magnitude of SBP lowering at each hour ranged from -3.68 mmHg to -17.74 mmHg (7 studies, 121 participants), DBP lowering at each hour ranged from -2.27 mmHg to -9.34 mmHg (7 studies, 121 participants), and HR lowering at each hour ranged from -0.29 beats/min to -10.29 beats/min (4 studies, 71 participants). When comparing between three 8-hourly time intervals that correspond to day, evening, and night time hours, BBPAA was less effective at lowering BP and HR at night, than during the day and evening. However, because we judged that these outcomes were supported by very low-certainty evidence, further research is likely to have an important impact on the estimate of effect and may change the conclusion.

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