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      Protective Effects of ACEI/ARB on Left Ventricular Function in Anthracycline-Induced Chronic Cardiotoxicity: A Meta-Analysis of Randomized Controlled Trials


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          Purpose: Cardiotoxicity is an important side effect of anthracycline. Cardioprotective drugs for anthracycline remain inconclusive. We attempted to determine the role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in the prevention of anthracycline-induced cardiotoxicity. Hypothesis: Prophylactic use of ACEI/ARB reduces the clinical or subclinical cardiotoxicity of anthracycline. Methods: Randomized controlled trials (RCTs) of ACEI/ARB in the prevention of anthracycline-induced cardiotoxicity were obtained by searching Pubmed, Embase, Web of Science, and Cochrane databases. 7 studies were finally included. A meta-analysis was performed on the 7 studies. The end points were changes in left ventricle ejection fraction (LVEF), early and late diastolic peak velocity ratio ( E/ A), and occurrence of hypotensive events. Results: Prophylactic use of ACEI/ARB has potential benefits for anthracycline-induced cardiotoxicity. LVEF was better preserved in the experimental group than in the control group (weighted mean difference [WMD] −3.16%, 95% confidence interval [CI] [−5.78, −0.54], p = 0.02). Follow-up time, tumor type, drug type, and geographical region did not affect the results. There was no significant benefit of E/ A in the experimental group (WMD 0.02, 95% CI [−0.06, 0.11], p = 0.58), and no increase in the incidence of hypotension (risk ratio 3.79, 95% CI [0.44, 32.89], p = 0.23). Conclusions: We found that prophylactic use of ACEI/ARB reduced the clinical or subclinical cardiotoxicity of anthracycline, and the increase in hypotensive events was not significant. Due to the relatively small number of clinical studies and participants, more related studies are necessary to further verify our results.

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          Most cited references32

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline.

            Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.
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              Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.

              Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity.

                Author and article information

                S. Karger AG
                July 2021
                04 May 2021
                : 146
                : 4
                : 469-480
                [_a] aDepartment of Oncology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
                [_b] bShantou University Medical College, Shantou, China
                [_c] cDepartment of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China
                Author information
                512848 Cardiology 2021;146:469–480
                © 2021 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.

                : 23 April 2020
                : 05 November 2020
                Page count
                Figures: 6, Tables: 3, Pages: 12
                Cardiovascular Prevention: Systematic Review

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Cardiotoxicity,Anthracyclines,Angiotensin-converting enzyme inhibitors,Meta-analysis,Angiotensin-receptor antagonists


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