Elsevier

The Lancet

Volume 366, Issue 9496, 29 October–4 November 2005, Pages 1545-1553
The Lancet

Articles
Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis

https://doi.org/10.1016/S0140-6736(05)67573-3Get rights and content

Summary

Background

β blockers have been used widely in the treatment of hypertension and are recommended as first-line drugs in hypertension guidelines. However, a preliminary analysis has shown that atenolol is not very effective in hypertension. We aim to substantially enlarge the data on atenolol and analyse the effect of different β blockers.

Methods

The Cochrane Library and PubMed were searched for β blocker treatment in patients with primary hypertension. Data were then entered into the Cochrane Collaboration Review Manager package and were summarised in meta-analyses. 13 randomised controlled trials (n=105 951) were included in a meta-analysis comparing treatment with β blockers with other antihypertensive drugs. Seven studies (n=27 433) were included in a comparison of β blockers and placebo or no treatment.

Findings

The relative risk of stroke was 16% higher for β blockers (95% CI 4–30%) than for other drugs. There was no difference for myocardial infarction. When the effect of β blockers was compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for all β blockers (7–29%), about half that expected from previous hypertension trials. There was no difference for myocardial infarction or mortality.

Interpretation

In comparison with other antihypertensive drugs, the effect of β blockers is less than optimum, with a raised risk of stroke. Hence, we believe that β blockers should not remain first choice in the treatment of primary hypertension and should not be used as reference drugs in future randomised controlled trials of hypertension.

Introduction

For three decades, β blockers have been widely used in the treatment of hypertension and are still recommended as first-line drugs in hypertension guidelines.1, 2 Moreover, after myocardial infarction and in patients with heart failure, treatment with β blockers prevents re-infarction, hospitalisation for heart failure, and premature death.3, 4, 5, 6 The effect of β blockers as a treatment for primary hypertension has been challenged.7, 8 A preliminary analysis has shown that atenolol is not very effective in hypertension.9 To avoid unnecessary harm to patients, the role of other β blockers needs to be investigated. Here, we substantially enlarge the data on atenolol and analyse the effect of different β blockers on stroke, myocardial infarction, and mortality of all causes (n=127 879).

Section snippets

Methods

The eligibility criteria for inclusion in the present meta-analyses were: randomised controlled trial; treatment of primary hypertension; β blocker as first-line antihypertensive drug in at least 50% of all patients in one treatment group; and outcome data for all-cause mortality, cardiovascular morbidity, or both. Data were then entered into the Cochrane Collaboration review manager programme (RevMan version 4.2). Heterogeneity between the studies was assessed with χ2 test and the chosen

Results

We identified 16 studies comparing β blockers with other antihypertensive treatment. Three of these studies were excluded: the large Captopril Prevention Project (CAPPP) study,11 comparing conventional treatment (diuretics and β blockers) with captopril, because the number of patients treated with β blockers was not registered (Lanke J, personal communication); the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial (comparing metoprolol with a thiazide diuretic) because that

Discussion

β blocker treatment of patients with primary hypertension was associated with a substantially higher risk of stroke than treatment with other antihypertensive agents. This was the case when all β blockers were analysed together and when the studies with atenolol were analysed separately. There was also a strong tendency in the same direction when the mixed trials were analysed. In the non-atenolol subgroup, documentation was poor, with surprisingly few studies and few clinical events. The

Search strategy and selection criteria

Initially, the Cochrane Library and PubMed were searched for systematic reviews of β blocker treatment in hypertensive patients ((“adrenergic β antagonists” [MeSH Terms] OR “adrenergic β antagonists” [Pharmacological Action] OR β blocker [Text Word]) AND (“hypertension” [MeSH Terms] OR hypertension [Text Word]) AND (“classification” [MeSH Terms] OR systematic [Text Word])) or ((“adrenergic β antagonists” [MeSH Terms] OR “adrenergic β antagonists” [Pharmacological Action] OR beta blocker

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