{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:16:55Z","timestamp":1784636215945,"version":"3.55.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":2384,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T00:00:00Z","timestamp":1562803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta-analysis aims to assess the efficacy of beta-blockers or angiotensin-converting enzyme (ACE) inhibitors\/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We systematically searched Pubmed, Cochrane, EMBASE, and Web of Science databases for randomized controlled trials published until February 2019. The analysis included randomized studies that reported on left ventricular ejection fraction (LVEF) after 6 months of chemotherapy in cancer patients who received beta-blockers or ACE inhibitors\/ARBs for prevention of cardiotoxicity compared with controls. Studies on combination cardioprotective therapies were excluded from the analysis. The primary endpoint was prevention of a decrease in LVEF as defined by the individual study and as assessed by either transthoracic echocardiography or magnetic resonance imaging. We here show that patients under anthracycline-based chemotherapy have a moderate yet significant benefit in LVEF from beta-blockers or ACEs\/ARBs. The beta-blocker analysis included 769 cancer patients, and the ACE inhibitors\/ARBs analysis included a total of 581 cancer patients. The mean LVEF difference between the beta-blocker group and the control group was 2.57% (95% confidence interval 0.63\u20134.51, P = 0.009). The mean difference for ACE inhibitors\/ARBs was 4.71% (95% confidence interval 0.38\u20139.03, P = 0.03). However, the beneficial effects throughout the studies were variable as documented by significant heterogeneity between the studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systematic evidence is needed to solidly found recommendations for cardioprotective prevention during chemotherapy. Likewise, trials on other neurohumoral drugs (spironolactone) and lipid-lowering approaches are required to improve protection for cardio-oncology patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12493","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T23:07:56Z","timestamp":1562886476000},"page":"856-862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Heart Failure from Cancer Therapy: Can we Prevent It?"],"prefix":"10.1093","volume":"6","author":[{"given":"Matthias","family":"Totzeck","sequence":"first","affiliation":[{"name":"Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen , Hufelandstr. 55, 45147, Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca I.","family":"Mincu","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen , Hufelandstr. 55, 45147, Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Heusch","sequence":"additional","affiliation":[{"name":"Institute for Pathophysiology, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen , Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tienush","family":"Rassaf","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen , Hufelandstr. 55, 45147, Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,11]]},"reference":[{"key":"2026012115092298400_ehf212493-bib-0001","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ijcard.2019.01.038","article-title":"Cardio-oncology\u2014strategies for management of cancer-therapy related cardiovascular disease","volume":"280","author":"Totzeck","year":"2019","journal-title":"Int J Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0002","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.hfc.2016.12.011","article-title":"How to develop a cardio-oncology clinic","volume":"13","author":"Snipelisky","year":"2017","journal-title":"Heart Fail Clin"},{"key":"2026012115092298400_ehf212493-bib-0003","doi-asserted-by":"crossref","first-page":"e445","DOI":"10.1016\/S1470-2045(17)30535-1","article-title":"Cardiotoxic effects of anthracycline-based therapy: what is the evidence and what are the potential harms?","volume":"18","author":"Levis","year":"2017","journal-title":"Lancet Oncol"},{"key":"2026012115092298400_ehf212493-bib-0004","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1161\/CIR.0000000000000556","article-title":"Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from the American Heart Association","volume":"137","author":"Mehta","year":"2018","journal-title":"Circulation"},{"key":"2026012115092298400_ehf212493-bib-0005","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1016\/j.jacc.2017.09.1096","article-title":"Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 1","volume":"70","author":"Chang","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0006","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/eurheartj\/ehw211","article-title":"ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)","volume":"37","author":"Zamorano","year":"2016","journal-title":"Eur Heart J"},{"key":"2026012115092298400_ehf212493-bib-0007","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1161\/CIRCULATIONAHA.118.039371","article-title":"Management of cardiovascular disease in women with breast cancer","volume":"139","author":"Barish","year":"2019","journal-title":"Circulation"},{"key":"2026012115092298400_ehf212493-bib-0008","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1177\/2047487318755193","article-title":"Cardiovascular diseases in patients receiving small molecules with anti-vascular endothelial growth factor activity: a meta-analysis of approximately 29,000 cancer patients","volume":"25","author":"Totzeck","year":"2018","journal-title":"Eur J Prev Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0009","doi-asserted-by":"crossref","DOI":"10.1038\/srep41530","article-title":"Preprocedural C-reactive protein predicts outcomes after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction a systematic meta-analysis","volume":"7","author":"Mincu","year":"2017","journal-title":"Sci Rep"},{"key":"2026012115092298400_ehf212493-bib-0010","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.117.006278","article-title":"Cardiovascular adverse events in patients with cancer treated with bevacizumab: a meta-analysis of more than 20 000 patients","volume":"6","author":"Totzeck","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2026012115092298400_ehf212493-bib-0011","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0","author":"Higgins"},{"key":"2026012115092298400_ehf212493-bib-0012","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"2026012115092298400_ehf212493-bib-0013","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1016\/j.jacc.2006.07.052","article-title":"Protective effects of carvedilol against anthracycline-induced cardiomyopathy","volume":"48","author":"Kalay","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0014","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1016\/j.ijcard.2012.06.023","article-title":"Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study","volume":"167","author":"Kaya","year":"2013","journal-title":"Int J Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0015","doi-asserted-by":"crossref","first-page":"509","DOI":"10.5603\/CJ.a2013.0150","article-title":"Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: a prospective randomized controlled study with six-month follow-up","volume":"21","author":"Elitok","year":"2014","journal-title":"Cardiol J"},{"key":"2026012115092298400_ehf212493-bib-0016","doi-asserted-by":"crossref","first-page":"725","DOI":"10.4103\/ijmr.IJMR_1323_14","article-title":"Preventive role of carvedilol in adriamycin-induced cardiomyopathy","volume":"144","author":"Jhorawat","year":"2016","journal-title":"Indian J Med Res"},{"key":"2026012115092298400_ehf212493-bib-0017","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1159\/000442722","article-title":"Carvedilol administration can prevent doxorubicin-induced cardiotoxicity: a double-blind randomized trial","volume":"134","author":"Tashakori Beheshti","year":"2016","journal-title":"Cardiology"},{"key":"2026012115092298400_ehf212493-bib-0018","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1016\/j.ihj.2018.06.011","article-title":"Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin","volume":"70","author":"Abuosa","year":"2018","journal-title":"Indian Heart J"},{"key":"2026012115092298400_ehf212493-bib-0019","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.jacc.2018.02.049","article-title":"Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial","volume":"71","author":"Avila","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0020","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.2147\/CMAR.S166481","article-title":"Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer","volume":"10","author":"Cochera","year":"2018","journal-title":"Cancer Manag Res"},{"key":"2026012115092298400_ehf212493-bib-0021","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1161\/CIRCULATIONAHA.106.635144","article-title":"Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition","volume":"114","author":"Cardinale","year":"2006","journal-title":"Circulation"},{"key":"2026012115092298400_ehf212493-bib-0022","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/2193-1801-2-198","article-title":"Long-term, up to 18 months, protective effects of the angiotensin II receptor blocker telmisartan on Epirubin-induced inflammation and oxidative stress assessed by serial strain rate","volume":"2","author":"Dessi","year":"2013","journal-title":"SpringerPlus"},{"key":"2026012115092298400_ehf212493-bib-0023","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1001\/jamaoncol.2016.1726","article-title":"Angiotensin II-receptor inhibition with candesartan to prevent trastuzumab-related cardiotoxic effects in patients with early breast cancer: a randomized clinical trial","volume":"2","author":"Boekhout","year":"2016","journal-title":"JAMA Oncol"},{"key":"2026012115092298400_ehf212493-bib-0024","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s12012-016-9365-z","article-title":"Effect of enalapril on preventing anthracycline-induced cardiomyopathy","volume":"17","author":"Janbabai","year":"2017","journal-title":"Cardiovasc Toxicol"},{"key":"2026012115092298400_ehf212493-bib-0025","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/ajh.21840","article-title":"Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up","volume":"85","author":"Georgakopoulos","year":"2010","journal-title":"Am J Hematol"},{"key":"2026012115092298400_ehf212493-bib-0026","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1200\/JCO.2016.68.7830","article-title":"Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-Breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity","volume":"35","author":"Pituskin","year":"2017","journal-title":"J Clin Oncol"},{"key":"2026012115092298400_ehf212493-bib-0027","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1016\/j.jacc.2013.02.072","article-title":"Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)","volume":"61","author":"Bosch","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0028","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1093\/eurheartj\/ehw022","article-title":"Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol","volume":"37","author":"Gulati","year":"2016","journal-title":"Eur Heart J"},{"key":"2026012115092298400_ehf212493-bib-0029","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/ejhf.196","article-title":"Protective effects of spironolactone against anthracycline-induced cardiomyopathy","volume":"17","author":"Akpek","year":"2015","journal-title":"Eur J Heart Fail"},{"key":"2026012115092298400_ehf212493-bib-0030","doi-asserted-by":"crossref","first-page":"S4386","DOI":"10.21037\/jtd.2018.11.110","article-title":"Modern concepts in cardio-oncology","volume":"10","author":"Rassaf","year":"2018","journal-title":"J Thoracic Dis"},{"key":"2026012115092298400_ehf212493-bib-0031","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1016\/j.jacc.2014.01.073","article-title":"Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review","volume":"63","author":"Thavendiranathan","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2026012115092298400_ehf212493-bib-0032","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejca.2018.02.005","article-title":"Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: the International CardioOncology Society-one trial","volume":"94","author":"Cardinale","year":"2018","journal-title":"Eur J Cancer"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fehf2.12493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.12493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.12493","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/6\/4\/856\/66136236\/eschf_6_4_856.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/6\/4\/856\/66136236\/eschf_6_4_856.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T20:12:10Z","timestamp":1769026330000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/6\/4\/856\/8403556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,11]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,7,11]]},"published-print":{"date-parts":[[2019,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.12493","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8]]},"published":{"date-parts":[[2019,7,11]]},"assertion":[{"value":"2018-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}