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2017 ; 1
(1
): CD002003
Nephropedia Template TP
Cochrane Database Syst Rev
2017[Jan]; 1
(1
): CD002003
PMID28107561
show ga
BACKGROUND: Beta-blockers refer to a mixed group of drugs with diverse
pharmacodynamic and pharmacokinetic properties. They have shown long-term
beneficial effects on mortality and cardiovascular disease (CVD) when used in
people with heart failure or acute myocardial infarction. Beta-blockers were
thought to have similar beneficial effects when used as first-line therapy for
hypertension. However, the benefit of beta-blockers as first-line therapy for
hypertension without compelling indications is controversial. This review is an
update of a Cochrane Review initially published in 2007 and updated in 2012.
OBJECTIVES: To assess the effects of beta-blockers on morbidity and mortality
endpoints in adults with hypertension. SEARCH METHODS: The Cochrane Hypertension
Information Specialist searched the following databases for randomized controlled
trials up to June 2016: the Cochrane Hypertension Specialised Register, the
Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE
(from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference
lists of relevant reviews, and reference lists of studies potentially eligible
for inclusion in this review, and also searched the the World Health Organization
International Clinical Trials Registry Platform on 06 July 2015. SELECTION
CRITERIA: Randomised controlled trials (RCTs) of at least one year of duration,
which assessed the effects of beta-blockers compared to placebo or other drugs,
as first-line therapy for hypertension, on mortality and morbidity in adults.
DATA COLLECTION AND ANALYSIS: We selected studies and extracted data in
duplicate, resolving discrepancies by consensus. We expressed study results as
risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or
random-effects meta-analyses, as appropriate. We also used GRADE to assess the
certainty of the evidence. GRADE classifies the certainty of evidence as high (if
we are confident that the true effect lies close to that of the estimate of
effect), moderate (if the true effect is likely to be close to the estimate of
effect), low (if the true effect may be substantially different from the estimate
of effect), and very low (if we are very uncertain about the estimate of effect).
MAIN RESULTS: Thirteen RCTs met inclusion criteria. They compared beta-blockers
to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241
participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and
renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These
RCTs were conducted between the 1970s and 2000s and most of them had a high risk
of bias resulting from limitations in study design, conduct, and data analysis.
There were 40,245 participants taking beta-blockers, three-quarters of them
taking atenolol. We found no outcome trials involving the newer vasodilating
beta-blockers (e.g. nebivolol).There was no difference in all-cause mortality
between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or
RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07,
95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all
comparisons.Total CVD was lower for beta-blockers compared to placebo (RR 0.88,
95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in
stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no
difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07;
moderate-certainty evidence). The effect of beta-blockers on CVD was worse than
that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was
not different from that of diuretics (moderate-certainty) or RAS inhibitors
(low-certainty). In addition, there was an increase in stroke in beta-blockers
compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and
RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence).
However, there was little or no difference in CHD between beta-blockers and
diuretics (low-certainty evidence), CCBs (moderate-certainty evidence) or RAS
inhibitors (low-certainty evidence). In the single trial involving participants
aged 65 years and older, atenolol was associated with an increased CHD incidence
compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking
beta-blockers were more likely to discontinue treatment due to adverse events
than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54;
moderate-certainty evidence), but there was little or no difference with placebo,
diuretics or CCBs (low-certainty evidence). AUTHORS' CONCLUSIONS: Most outcome
RCTs on beta-blockers as initial therapy for hypertension have high risk of bias.
Atenolol was the beta-blocker most used. Current evidence suggests that
initiating treatment of hypertension with beta-blockers leads to modest CVD
reductions and little or no effects on mortality. These beta-blocker effects are
inferior to those of other antihypertensive drugs. Further research should be of
high quality and should explore whether there are differences between different
subtypes of beta-blockers or whether beta-blockers have differential effects on
younger and older people.
|Adrenergic beta-Antagonists/adverse effects/*therapeutic use
[MESH]
|Adult
[MESH]
|Aged
[MESH]
|Angiotensin Receptor Antagonists/therapeutic use
[MESH]
|Antihypertensive Agents/adverse effects/*therapeutic use
[MESH]
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