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Meta-Analysis
. 2014 Feb 28;2014(2):CD007452.
doi: 10.1002/14651858.CD007452.pub2.

Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension

Gavin W K Wong  1 , James M Wright
Affiliations
Meta-Analysis

Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension

Gavin W K Wong et al. Cochrane Database Syst Rev. .

Abstract

Background: Beta-blockers are one of the classes of drugs frequently used to treat hypertension. Quantifying the blood pressure (BP) lowering effects of nonselective beta-blockers provides important information that aids clinical decision making.

Objectives: To quantify the dose-related effects of nonselective beta-adrenergic receptor blockers (beta-blockers) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) as compared with placebo in people with primary hypertension.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2013.

Selection criteria: Randomized, double-blind, placebo-controlled, parallel or cross-over trials. Studies had to contain a nonselective beta-blocker monotherapy arm with a fixed dose. Participants enrolled into the studies had to have primary hypertension at baseline. Duration of studies had to be between three and 12 weeks.

Data collection and analysis: Two review authors (GW and AL) independently confirmed the inclusion of studies and extracted the data.

Main results: We included 25 RCTs that evaluated the BP lowering effects of seven nonselective beta-blockers in 1264 people with hypertension. Among the 25 RCTs, four were parallel studies and 21 were cross-over studies. Overall, nonselective beta-blockers lowered systolic BP and diastolic BP compared with placebo. Nonselective beta-blockers, in the recommended dose range, did not showed a convincing dose-response relationship by direct comparison. The once (1x) and twice (2x) starting dose subgroups contained the largest sample size. The estimate of BP lowering efficacy for nonselective beta-blockers by combining the 1x and 2x starting dose subgroup was -10 mmHg (95% CI -11 to -8) for systolic BP and -7 mmHg (95% CI -8 to -6) for diastolic BP (low-quality evidence). Nonselective beta-blockers starting at the 1x recommended starting doses lowered heart rate by 12 beats per minute (95% CI 10 to 13) (low-quality evidence). The dose-response relationship in heart rate was evident by both direct and indirect comparison. Due to imprecision, there was no clear evidence of an effect of nonselective beta-blockers on pulse pressure in any dose subgroups except for a small reduction with the 2x starting dose (-2.2 mmHg, 95% CI -3.7 to -0.7) (very low quality evidence). The point estimates in the 1x, four times (4x) and eight times (8x) starting dose subgroups were similar to the 2x starting dose subgroup. Therefore, it would appear that if nonselective beta-blockers do lower pulse pressure, the magnitude is likely to be about 2 mmHg. There were very limited data (two studies) on withdrawals due to adverse effects (risk ratio (RR) 0.84; 95% CI 0.38 to 1.82).

Authors' conclusions: In people with mild-to-moderate hypertension, nonselective beta-blockers lowered peak BP by a mean of -10/-7 mmHg (systolic/diastolic) and reduced heart rate by 12 beats per minute. Propranolol and penbutolol were the two drugs that contributed to most of the data for nonselective beta-blockers. This estimate is likely exaggerated due to the presence of extreme outliers and other sources of bias. If we removed the extreme outliers from the analysis, the estimate for non-selective beta-blockers was lower (-8/-5 mmHg (systolic/diastolic)). Nonselective beta-blockers did not show a convincing graded dose-response in the recommended dose range for systolic BP and diastolic BP, while higher dose nonselective beta-blockers provided greater reduction of heart rate. Using higher dose nonselective beta-blockers might cause more side effects, such as bradycardia, without producing an additional BP lowering effect. The effect of nonselective beta-blockers on pulse pressure was likely small, at about 2 mmHg.

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Conflict of interest statement

None known.

Figures

1
1
PRISMA diagram.
2
2
3
3
Funnel plot of systolic blood pressure of 2x starting dose propranolol.
4
4
Funnel plot of diastolic blood pressure of 2x starting dose propranolol.
1.1
1.1. Analysis
Comparison 1 Propranolol versus placebo, Outcome 1 Systolic blood pressure.
1.2
1.2. Analysis
Comparison 1 Propranolol versus placebo, Outcome 2 Diastolic blood pressure.
1.3
1.3. Analysis
Comparison 1 Propranolol versus placebo, Outcome 3 Heart rate.
1.4
1.4. Analysis
Comparison 1 Propranolol versus placebo, Outcome 4 Pulse pressure.
1.5
1.5. Analysis
Comparison 1 Propranolol versus placebo, Outcome 5 Direct comparison 2x doses.
2.1
2.1. Analysis
Comparison 2 Timolol versus placebo, Outcome 1 Systolic blood pressure.
2.2
2.2. Analysis
Comparison 2 Timolol versus placebo, Outcome 2 Diastolic blood pressure.
2.3
2.3. Analysis
Comparison 2 Timolol versus placebo, Outcome 3 Heart rate.
2.4
2.4. Analysis
Comparison 2 Timolol versus placebo, Outcome 4 Pulse pressure.
3.1
3.1. Analysis
Comparison 3 Penbutolol versus placebo, Outcome 1 Systolic blood pressure.
3.2
3.2. Analysis
Comparison 3 Penbutolol versus placebo, Outcome 2 Diastolic blood pressure.
3.3
3.3. Analysis
Comparison 3 Penbutolol versus placebo, Outcome 3 Heart rate.
3.4
3.4. Analysis
Comparison 3 Penbutolol versus placebo, Outcome 4 Pulse pressure.
4.1
4.1. Analysis
Comparison 4 Tertatolol versus placebo, Outcome 1 Systolic blood pressure.
4.2
4.2. Analysis
Comparison 4 Tertatolol versus placebo, Outcome 2 Diastolic blood pressure.
4.3
4.3. Analysis
Comparison 4 Tertatolol versus placebo, Outcome 3 Heart rate.
4.4
4.4. Analysis
Comparison 4 Tertatolol versus placebo, Outcome 4 Pulse pressure.
5.1
5.1. Analysis
Comparison 5 Indenolol versus placebo, Outcome 1 Heart rate.
6.1
6.1. Analysis
Comparison 6 Nadolol versus placebo, Outcome 1 Heart rate.
7.1
7.1. Analysis
Comparison 7 Moprolol versus placebo, Outcome 1 Heart rate.
8.1
8.1. Analysis
Comparison 8 Pooled subclass effects (NSBB: nonselective beta‐blocker), Outcome 1 Systolic blood pressure.
8.2
8.2. Analysis
Comparison 8 Pooled subclass effects (NSBB: nonselective beta‐blocker), Outcome 2 Diastolic blood pressure.
8.3
8.3. Analysis
Comparison 8 Pooled subclass effects (NSBB: nonselective beta‐blocker), Outcome 3 Heart rate.
8.4
8.4. Analysis
Comparison 8 Pooled subclass effects (NSBB: nonselective beta‐blocker), Outcome 4 Pulse pressure.
8.5
8.5. Analysis
Comparison 8 Pooled subclass effects (NSBB: nonselective beta‐blocker), Outcome 5 Withdrawal due to adverse effects.
8.6
8.6. Analysis
Comparison 8 Pooled subclass effects (NSBB: nonselective beta‐blocker), Outcome 6 Combined 1x and 2x starting dose estimates.
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