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J Am Coll Cardiol, 2009; 53:2101-2102, doi:10.1016/j.jacc.2008.11.067
© 2009 by the American College of Cardiology Foundation
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CORRESPONDENCE: LETTER TO THE EDITOR

Atenolol Versus Other Beta-Adrenergic Blockers

Ivar Aursnes, MD, PhD* and Jan-Bjørn Osnes, MD, PhD

* Department of Pharmacology, University of Oslo, P.O. Box 1057 Blindern, Oslo, N-0316, Norway (Email: i.a.aursnes{at}medisin.uio.no).


The question is: Does atenolol differ from other beta-adrenergic blockers in clinical outcome? Bangalore et al. (1) nicely related unfavorable trial outcomes to the degree of pulse rate reduction induced by beta-adrenergic blockers. But is it not a mistake to include the HAPPHY (Heart Attack Primary Prevention in Hypertension) trial without considering that the 2 beta-adrenergic blockers arms differed as to outcome (2)? Patients on atenolol showed higher death rates and patients on metoprolol showed lower death rates than did patients taking diuretics. The difference between the 2 outcomes was not by itself statistically significant (results with other end points were neither reported nor provided on request). But together with a borderline significant difference between atenolol and other beta-adrenergic blockers in a meta-analysis of beta-adrenergic blockers in hypertension using a Bayesian approach (3) without including the HAPPHY trial, we do think that atenolol is inferior to other beta-adrenergic blockers. It should be underscored that atenolol differs markedly from most other beta-adrenergic blockers by being water soluble and thus almost unable to enter the central nervous system. This seems to explain why atenolol did not stimulate the vagal nerves by an action in the central nervous system, as metoprolol did (4).

We therefore suggest that the conclusion drawn by Bangalore et al. (1) should be restricted to atenolol only. Atenolol does not seem to be an appropriate representative for the whole class of beta-adrenergic blockers, although unfortunately it is widely used. This should be considered when interpreting results from clinical trials on beta-adrenergic blockers and when designing new trials.


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1. Bangalore S, Sawhney S, Messerli FH. Relation of beta-blocker–induced heart rate lowering and cardioprotection in hypertension J Am Coll Cardiol 2008;52:1482-1489.[Abstract/Free Full Text]

2. Holme I. MAPHY and the two arms of HAPPHY JAMA 1989;262:3272-3274.[Abstract/Free Full Text]

3. Aursnes I, Osnes JB, Tvete I, Gasemyr J, Natvig B. Does atenolol differ from other beta-adrenergic blockers? BMC Clin Pharmacol 2007;7:4.[CrossRef][Medline]

4. Åblad B, Bjurö T, Björkman JA, Edström T. Prevention of ventricular fibrillation requires central β-adrenoceptor blockade in rabbits Scand Cardiovasc J 2007;41:221-229.[CrossRef][Web of Science][Medline]


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Franz H. Messerli and Sripal Bangalore
J. Am. Coll. Cardiol. 2009 53: 2106-2107. [Full Text] [PDF]




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