How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis

Stellenbosch University, Johannesburg, Gauteng, South Africa
Journal of Hypertension (Impact Factor: 4.72). 12/2006; 24(11):2131-41. DOI: 10.1097/01.hjh.0000249685.58370.28
Source: PubMed


To quantify the effect of first-line antihypertensive treatment with beta-blockers on mortality, morbidity and withdrawal rates, compared with the other main classes of antihypertensive agents.
We identified eligible trials by searching the Cochrane Controlled Trials Register, Medline, Embase, reference lists of previous reviews, and contacting researchers. We extracted data independently in duplicate and conducted meta-analysis by analysing trial participants in groups to which they were randomized, regardless of subsequent treatment actually received.
Thirteen trials with 91,561 participants, meeting inclusion criteria, compared beta-blockers to placebo (four trials; n = 23,613), diuretics (five trials; n = 18,241), calcium-channel blockers (CCBs) (four trials; n = 44,825), and renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (three trials; n = 10,828). Compared to placebo, beta-blockers reduced the risk of stroke (relative risk 0.80; 95% confidence interval 0.66-0.96) with a marginal fall in total cardiovascular events (0.88, 0.79-0.97), but did not affect all-cause mortality (0.99, 0.88-1.11), coronary heart disease (0.93, 0.81-1.07) or cardiovascular mortality (0.93, 0.80-1.09). The effect on stroke was less than that of CCBs (1.24, 1.11-1.40) and RAS inhibitors (1.30, 1.11-1.53), and that on total cardiovascular events less than that of CCBs (1.18, 1.08-1.29). In addition, patients on beta-blockers were more likely to discontinue treatment than those on diuretics (1.80; 1.33-2.42) or RAS inhibitors (1.41; 1.29-1.54).
Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. Compared with diuretics, they had similar outcomes, but were less well tolerated. Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.

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    • "The place of β-blockers in the treatment of hypertension is controversial. This is partly based on the finding that these agents are less effective in reducing the incidence of stroke [60] [61], myocardial infarction and death than are other antihypertensives [61] [62]. These findings are complicated by the diversity of β-blockers that have varying pharmacological properties. "

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    • "1.05 (0.96–1.15) 1.24 (1.11–1.40) Bradley et al., 2006 (12) Overall 4 1.07 (1.00–1.14) 1.05 (0.96–1.15) 1.24 (1.11–1.40) "
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    ABSTRACT: For more than 3 decades, beta-blockers have been widely used in the treatment of hypertension and are still recommended as first-line agents by national and international guidelines. Recent meta-analyses indicate that, in patients with uncomplicated hypertension, compared with other antihypertensive agents, first-line therapy with beta-blockers was associated with an increased risk of stroke, especially in the elderly cohort with no benefit for the end points of all-cause mortality, cardiovascular morbidity, and mortality. In this review, we critically analyze the evidence supporting the use of beta-blockers in patients with hypertension and evaluate evidence for its role in other indications. The review of the currently available literature shows that in patients with uncomplicated hypertension, there is a paucity of data or absence of evidence to support use of beta-blockers as monotherapy or as first-line agents. Given the increased risk of stroke, their "pseudo-antihypertensive" efficacy (failure to lower central aortic pressure), lack of effect on regression of target end organ effects like left ventricular hypertrophy and endothelial dysfunction, and numerous adverse effects, the risk benefit ratio for beta-blockers is not acceptable for this indication. However, beta-blockers remain very efficacious agents for the treatment of heart failure, certain types of arrhythmia, hypertropic obstructive cardiomyopathy, and in patients with prior myocardial infarction.
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