CORRESPONDENCE: LETTER TO THE EDITOR
Different Metabolic Effects of Selective and Nonselective Beta-Blockers Rather Than Mere Heart Rate Reduction May Be the Mechanisms by Which Beta-Blockade Prevents Cardiovascular Events
Gabriele Fragasso, MD*,
Michela Cera, MD and
Alberto Margonato, MD
* Istituto Scientifico San Raffaele, Milan, Italy, Clinical Cardiology-Heart Failure Clinic, via Olgettina 60, Milan 20132, Italy (Email: gabriele.fragasso{at}hsr.it).
We read with interest the article by Bangalore et al. (1), who analyzed in 9 trials the role of pharmacologic reduction of heart rate (HR) using beta-blockers in preventing cardiovascular events in patients with hypertension. Beta-blocker–induced lower HR was associated with greater mortality and morbidity risk. As the basis of worse outcomes with "beta-blockers," the authors recognize only an increase in central aortic/pulse pressure with pharmacologic HR lowering. Even though they acknowledge that the beta-blocker used in the studies was mainly atenolol, and hence, any extrapolation of these results to other beta-blockers should be done with caution, the whole paper and the accompanying editorial just generically refer to "beta-blockade." In fact, the mechanisms by which beta-blockers improve prognosis in different cardiac contexts are probably multiple. Improved energy efficiency seen with some beta-blockers (2) could be one of the reasons for better survival observed with their use (3). Additionally, central inhibition of sympathetic activity with moxonidine in heart failure, despite a significant reduction of HR, has been associated with increased mortality (4). In fact, moxonidine has been shown to alter myocardial metabolism (5). This could be the reason for the failure of central sympathetic inhibition to prevent deaths in patients with heart failure and also indicates that the predominant mechanism of action of "effective" beta-blockers is probably related to mechanisms other than mere HR reduction. In fact, apart from reducing HR, atenolol and most selective beta-blockers impair endothelial function, decrease insulin sensitivity, and increase lipid levels (6), all conditions that may worsen the global risk profile. Conversely, new generation beta-blockers have been seen to improve metabolism and endothelial function (7). Therefore, HR reduction in itself, especially if associated with a bulk of deleterious metabolic and vascular effects, is definitely not enough to improve prognosis. The alarm created by the Bangalore et al. (1) paper should be clearly confined to selective beta-blockers and not generically extended to the whole drug class.
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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. Podbregar M, Voga G. Effect of selective and nonselective beta-blockers on resting energy production rate and total body substrate utilization in chronic heart failure J Cardiac Fail 2002;8:369-378.[CrossRef][Web of Science][Medline] 3. Poole-Wilson P, Swedberg K, Cleland J, et al. Carvedilol or Metoprolol European Trial Investigators Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial Lancet 2003;362:7-13.[CrossRef][Web of Science][Medline] 4. Wiltse C, Wright T, MOXCON Investigators Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON) Eur J Heart Fail 2003;5:659-666.[Abstract/Free Full Text] 5. Mobini R, Jansson PA, Bergh CH, Sharing Tang M, Waagstein F, Andersson B. Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine Clin Sci 2006;110:329-336.[CrossRef][Web of Science][Medline] 6. Lithell HO. Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism Diabetes Care 1991;14:203-209.[Abstract] 7. Celik T, Iyisoy A, Kursaklioglu H, et al. Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients J Hypertens 2006;24:591-596.[Web of Science][Medline]
Related Article
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Reply
- Franz H. Messerli and Sripal Bangalore
J. Am. Coll. Cardiol. 2009 53: 2106-2107.
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