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      Efficacy of I f Inhibition with Ivabradine in Different Subpopulations with Stable Angina Pectoris

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          Abstract

          Objectives: The antianginal and anti-ischemic efficacy of ivabradine has been demonstrated in large-scale trials. Pooling trial data allowed for subpopulation analyses of ivabradine’s antianginal efficacy. Methods: Data on the frequency of angina attacks, short-acting nitrate consumption, and heart rate were pooled from 5 randomized trials in patients with stable angina pectoris receiving 5, 7.5, or 10 mg of ivabradine b.i.d. for 3 or 4 months. The subpopulations were defined according to age, sex, disease characteristics, and comorbidities (severity of angina, history of myocardial infarction, cerebrovascular disease, revascularization status, diabetes, asthma/chronic obstructive pulmonary disease, or peripheral vascular disease). Results: Efficacy data were available for 2,425 patients (full analysis set), in whom ivabradine reduced the frequency of diary-based angina attacks by 59.4% and nitrate consumption by 53.7%. All subpopulations experienced 51–70% reductions in the frequency of angina attacks, with similar reductions for the other parameters studied. Ivabradine’s efficacy was maintained in the presence of different comorbidities. In the safety set, ivabradine reduced heart rate by 14.5%. Ivabradine had a good safety and tolerability profile in all the subpopulations assessed. Conclusions: The antianginal efficacy of ivabradine was consistent across all the subpopulations analyzed, independent of the severity of angina and the presence of a comorbidity.

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          Most cited references23

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          Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology.

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            Representation of elderly persons and women in published randomized trials of acute coronary syndromes.

            Elderly persons and women were underrepresented in randomized controlled trials (RCTs) prior to 1990. Since then, efforts have been made to correct these biases, but their effect is unclear. To determine whether the percentage of elderly persons and women in published clinical trials of acute coronary syndromes has increased and how this enrollment compared with disease prevalence. The MEDLINE and Cochrane databases were searched for English-language articles from January 1966 to March 2000 regarding myocardial infarction, unstable angina, or acute coronary syndromes. Additional data sources included meta-analyses, review articles, and cardiology textbooks. Estimates of community-based myocardial infarction rates came from the National Registry of Myocardial Infarction and the Worcester Heart Study. Published RCTs of acute coronary syndrome patients were included and trials enrolling 50 patients or fewer, those without clinical end points, papers published in a language other than English, and unpublished manuscripts were excluded. Of 7645 studies identified, 593 RCTs were selected for review. The RCTs were abstracted by 2 of the authors for year of publication, source of support (ie, funding), pharmacotherapy, study phase, number of study sites, trial location, number of patients, mean age of the study population, and any age exclusion criteria for enrollment. The number of published RCTs with explicit age exclusions has declined from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients aged 75 years or older increased from 2% for studies published during 1966-1990 to 9% during 1991-2000, but remains well below their representation among all patients with myocardial infarction (37%) in the United States. Enrollment of women has risen from 20% for studies published between 1966-1990 to 25% during 1991-2000, but remains well below their proportion of all patients with myocardial infarction (43%) in the United States. Attempts at making cardiovascular RCTs more inclusive appear to have had limited success; thus, women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence. Because safety and efficacy can vary as a function of sex and age, these enrollment biases undermine efforts to provide evidence-based care to all cardiac patients.
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              Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.

              Ivabradine, a new I(f) inhibitor which acts specifically on the pacemaker activity of the sinoatrial node, is a pure heart rate lowering agent. Ivabradine has shown anti-ischaemic and anti-anginal activity in a placebo-controlled trial. The objective of this study was to compare the anti-anginal and anti-ischaemic effects of ivabradine and the beta-blocker atenolol. In a double-blinded trial, 939 patients with stable angina were randomized to receive ivabradine 5 mg bid for 4 weeks and then either 7.5 or 10 mg bid for 12 weeks or atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks. Patients underwent treadmill exercise tests at randomization (M(0)) and after 4 (M(1)) and 16 (M(4)) weeks of therapy. Increases in total exercise duration (TED) at trough at M(4) were 86.8+/-129.0 and 91.7+/-118.8 s with ivabradine 7.5 and 10 mg, respectively and 78.8+/-133.4 s with atenolol 100 mg. Mean differences (SE) when compared with atenolol 100 mg were 10.3 (9.4) and 15.7 (9.5) s in favour of ivabradine 7.5 and 10 mg (P<0.001 for non-inferiority). TED at M(1) improved by 64.2+/-104.0 s with ivabradine 5 mg and by 60.0+/-114.4 s with atenolol 50 mg (P<0.001 for non-inferiority). Non-inferiority of ivabradine was shown at all doses and for all criteria. The number of angina attacks was decreased by two-thirds with both ivabradine and atenolol. Ivabradine is as effective as atenolol in patients with stable angina.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2009
                August 2009
                26 May 2009
                : 114
                : 2
                : 116-125
                Affiliations
                a3rd Division of Cardiology, Medical University of Silesia, Katowice, Poland; bState University of New York Downstate Health Science Center at Brooklyn, Brooklyn,N.Y., USA; cMontreal Heart Institute, Université de Montréal, Montreal, Que., Canada
                Article
                219938 Cardiology 2009;114:116–125
                10.1159/000219938
                19468225
                55e21540-fd38-4971-9604-f557574edfb4
                © 2009 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.

                History
                : 23 January 2009
                : 11 March 2009
                Page count
                Figures: 2, Tables: 5, References: 35, Pages: 10
                Categories
                Original Research

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Ivabradine,Angina pectoris,Antianginal efficacy

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