David Austin MBChB, MD , Rebecca H. Maier MSc , Nasima Akhter PhD , Mohammad Sayari MSc , Emmanuel Ogundimu PhD , Jamie M. Maddox MBChB , Sharareh Vahabi MBChB, MD , Alison C. Humphreys MBBcH, MD , Janine Graham MBChB , Helen Oxenham MBChB, MD , Sophie Haney MBBS , Nicola Cresti MD, PhD , Mark Verrill MB, BChir , Wendy Osborne MBBS , Kathryn L. Wright MBChB , Rebecca Goranova MBBS , James R. Bailey MBBS, PhD , Nagesh Kalakonda MBBS, PhD , Mac Macheta MBChB , Mari F. Kilner MBChB , Chris Plummer BM, BCh, PhD
{"title":"Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma","authors":"David Austin MBChB, MD , Rebecca H. Maier MSc , Nasima Akhter PhD , Mohammad Sayari MSc , Emmanuel Ogundimu PhD , Jamie M. Maddox MBChB , Sharareh Vahabi MBChB, MD , Alison C. Humphreys MBBcH, MD , Janine Graham MBChB , Helen Oxenham MBChB, MD , Sophie Haney MBBS , Nicola Cresti MD, PhD , Mark Verrill MB, BChir , Wendy Osborne MBBS , Kathryn L. Wright MBChB , Rebecca Goranova MBBS , James R. Bailey MBBS, PhD , Nagesh Kalakonda MBBS, PhD , Mac Macheta MBChB , Mari F. Kilner MBChB , Chris Plummer BM, BCh, PhD","doi":"10.1016/j.jaccao.2024.07.010","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.</div></div><div><h3>Objectives</h3><div>The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.</div></div><div><h3>Methods</h3><div>This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m<sup>2</sup> doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.</div></div><div><h3>Results</h3><div>Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.</div></div><div><h3>Conclusions</h3><div>Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; <span><span>NCT03265574</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"6 5","pages":"Pages 684-696"},"PeriodicalIF":12.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jacc: Cardiooncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666087324002655","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.
Objectives
The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.
Methods
This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.
Results
Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.
Conclusions
Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)
期刊介绍：
JACC: CardioOncology is a specialized journal that belongs to the esteemed Journal of the American College of Cardiology (JACC) family. Its purpose is to enhance cardiovascular care for cancer patients by publishing high-quality, innovative scientific research and sharing evidence-based knowledge.
The journal aims to revolutionize the field of cardio-oncology and actively involve and educate professionals in both cardiovascular and oncology fields. It covers a wide range of topics including pre-clinical, translational, and clinical research, as well as best practices in cardio-oncology. Key areas of focus include understanding disease mechanisms, utilizing in vitro and in vivo models, exploring novel and traditional therapeutics (across Phase I-IV trials), studying epidemiology, employing precision medicine, and investigating primary and secondary prevention.
Amyloidosis, cardiovascular risk factors, heart failure, and vascular disease are some examples of the disease states that are of particular interest to the journal. However, it welcomes research on other relevant conditions as well.
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