Blood pressure lowering efficacy of nonselective beta-blockers for primary
hypertension.
Author(s): Wong GW(1), Wright JM.
Affiliation(s): Author information:
(1)Department of Anesthesiology, Pharmacology and Therapeutics, University of
British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Publication date & source: 2014, Cochrane Database Syst Rev. , 2:CD007452
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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