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      The Anti-Ischemic Effect of Metoprolol in Patients with Chronic Angina Pectoris Is Gender-Specific

      ,

      Cardiology

      S. Karger AG

      Coronary heart disease, Metroprolol, Gender differences

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          Abstract

          Several gender-specific differences in cardiovascular diseases are known and pharmacokinetics of β-blockers shows relevant sex-specific differences. The plasma levels of metoprolol, for example, are higher in women compared to men. However, randomized studies have shown that metoprolol has little or no greater reduction in the mortality of women following myocardial infarction. We tested the hypothesis that metoprolol might have significant gender-specific effects in patients with chronic angina pectoris. Body weight of women was slightly (–9%) less than that of men and the daily dose of metoprolol was similar in both groups. Thus, according to pharmacokinetics women should have obtained higher plasma levels of this drug and the ensuing pharmacologic effects of metoprolol should have been greater. Our results do not confirm this assumption. Metoprolol reduced the frequency of angina episodes and the consumption of nitroglycerin tablets to a similar extent in both sexes. However, the pretreatment hemodynamic profiles confirmed the existence of gender-specific differences: women had significantly higher heart rate and blood pressure both at rest and during exercise. Since both groups were comparable in age, comorbidities, and medications, the existing difference is likely to be due to gender-specificity. The hemodynamic differences persisted during therapy with metoprolol: resting heart rate, blood pressure and rate pressure product were reduced to a greater extent in men. During cycloergometry, there was a slight difference in the time of onset of ST depression and time of onset of angina, which were slightly higher in men, but probably because of the limited number of cases, the difference between men and women did not reach significance. On the other hand, with metoprolol the duration of exercise and, in parallel, the number of metabolic equivalents was significantly greater in males than in females. Thus in spite of a presumed greater plasma concentration of metoprolol in women, we found a significant difference in anti-ischemic effect in favor of men. We conclude that metoprolol might exert a significantly greater therapeutic effect on stress-induced angina pectoris in men than in women and this difference should be taken into account when prescribing this β-blocker.

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          Most cited references 8

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          Coronary atherogenic risk factors in women.

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            Estrogenic hormone action in the heart: regulatory network and function.

            Cardiovascular diseases are the leading cause of death in the industrialised countries and display significant gender-based differences. Estrogen plays an important role in the pathogenesis of heart disease and is able to modulate the progression of cardiovascular disease. The focus on the beneficial influence of estrogen is gradually shifting from the vascular system to the myocardium. The presence of functional estrogen receptors in the myocardium has been demonstrated. Estrogen is important for cardiovascular baseline physiology and modulates the myocardial response under pathological conditions. Here we summarise the current knowledge of the regulatory network of estrogenic action in the myocardium and its effects on cardiovascular function.
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              Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases.

              Differences in pharmacokinetics, pharmacodynamics, and physiology contribute to the phenomenon that women and men frequently respond differently to cardiovascular drugs. Hormonal influences, in addition, can play an important role: for example, the menstrual cycle, menopause, and pregnancy--as a result of fluctuations in concentrations of sexual steroids, and of changes in total body water--can be associated with gender-specific differences in the plasma levels of cardiovascular drugs. Clinical relevance accordingly results, especially for substances with a narrow therapeutic margin. This review treats the most important pharmacodynamic gender-relevant differences in this context, and surveys available evidence on the benefits of therapy of chronic cardiovascular diseases in women. On the whole, the study situation for women is appreciably less favourable than for men: owing to the fact that women are under-represented in most studies, and that few gender-specific analyses have been conducted.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2006
                September 2006
                29 September 2006
                : 106
                : 3
                : 147-153
                Affiliations
                Cardiology Office, Rheinfelden, Switzerland
                Article
                92769 Cardiology 2006;106:147–153
                10.1159/000092769
                16636544
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 3, References: 23, Pages: 7
                Categories
                Original Research

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