Elsevier

The Lancet

Volume 364, Issue 9446, 6–12 November 2004, Pages 1684-1689
The Lancet

Articles
Atenolol in hypertension: is it a wise choice?

https://doi.org/10.1016/S0140-6736(04)17355-8Get rights and content

Summary

Background

Atenolol is one of the most widely used β blockers clinically, and has often been used as a reference drug in randomised controlled trials of hypertension. However, questions have been raised about atenolol as the best reference drug for comparisons with other antihypertensives. Thus, our aim was to systematically review the effect of atenolol on cardiovascular morbidity and mortality in hypertensive patients.

Methods

Reports were identified through searches of The Cochrane Library, MEDLINE, relevant textbooks, and by personal communication with established researchers in hypertension. Randomised controlled trials that assessed the effect of atenolol on cardiovascular morbidity or mortality in patients with primary hypertension were included.

Findings

We identified four studies that compared atenolol with placebo or no treatment, and five that compared atenolol with other antihypertensive drugs. Despite major differences in blood pressure lowering, there were no outcome differences between atenolol and placebo in the four studies, comprising 6825 patients, who were followed up for a mean of 4·6 years on all-cause mortality (relative risk 1·01 [95% CI 0·89–1·15]), cardiovascular mortality (0·99 [0·83–1·18]), or myocardial infarction (0·99 [0·83–1·19]). The risk of stroke, however, tended to be lower in the atenolol than in the placebo group (0·85 [0·72–1·01]). When atenolol was compared with other antihypertensives, there were no major differences in blood pressure lowering between the treatment arms. Our meta-analysis showed a significantly higher mortality (1·13 [1·02–1·25]) with atenolol treatment than with other active treatment, in the five studies comprising 17671 patients who were followed up for a mean of 4·6 years. Moreover, cardiovascular mortality also tended to be higher with atenolol treatment than with other antihypertensive treatment. Stroke was also more frequent with atenolol treatment.

Interpretation

Our results cast doubts on atenolol as a suitable drug for hypertensive patients. Moreover, they challenge the use of atenolol as a reference drug in outcome trials in hypertension.

Introduction

β blockers have long been considered to be well documented first-line drugs in the treatment of hypertension.1 Moreover, atenolol is one of the most widely used β blockers clinically, and it has often been used as a reference drug in randomised controlled trials of hypertension.2, 3, 4, 5 Questions have been raised about β blockers as first-line treatment options in hypertension.6 In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial, losartan was shown to be more effective than atenolol in hypertensive patients with left ventricular hypertrophy.4 Whether the result of the LIFE study was caused by a beneficial effect of losartan or a weak effect of atenolol on cardiovascular disease, or both, has been debated.7 The effect of atenolol after myocardial infarction has also been questioned.8 Hence, the aim of our investigation was to systematically review the effect of atenolol on cardiovascular morbidity and mortality in hypertensive individuals.

Section snippets

Methods

We reviewed randomised controlled trials that assessed the effect of atenolol on cardiovascular morbidity or mortality in patients with primary hypertension. Studies were identified though searching of The Cochrane Library, MEDLINE, textbooks, and by personal communication with established researchers in hypertension. The following keywords were used in the database search: atenolol (MESH) OR atenolol “text” AND cerebrovascular disorders (MESH) OR myocardial infarction (MESH); atenolol AND

Results

17 randomised controlled trials were identified in which atenolol was used in one of the treatment arms of hypertension (panel). Five studies were excluded since atenolol was one of two or more drug alternatives in the same treatment arm.9, 10, 11, 12, 13 One was excluded since it compared multidrug strategies rather than individual agents.14 Three studies were excluded since atenolol was an add-on drug.15, 16, 17

In two studies that were included,18, 19 the population of interest was patients

Discussion

The present analysis casts doubts on atenolol as a suitable first-line drug for hypertensive patients. Moreover, it challenges the use of atenolol as a reference drug in outcome trials in hypertension. It is noteworthy that the superiority of atenolol over placebo or no treatment in reducing blood pressure did not result in a beneficial effect on mortality or myocardial infarction. The only study showing an advantage for atenolol was the open HEP study, in which one of the outcome variables—ie,

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