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Lookup NU author(s): Dr David Austin, Rebecca Maier, Dr Nicola Cresti, Dr Mark Verrill, Dr Wendy Osborne, Dr Kathryn Wright, Victoria Hildreth, Jon Prichard, Professor Adetayo Kasim, Professor Helen HancockORCiD, Dr Chris PlummerORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The AuthorsBackground: 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)
Author(s): Austin D, Maier RH, Akhter N, Sayari M, Ogundimu E, Maddox JM, Vahabi S, Humphreys AC, Graham J, Oxenham H, Haney S, Cresti N, Verrill M, Osborne W, Wright KL, Goranova R, Bailey JR, Kalakonda N, Macheta M, Kilner MF, Young ME, Morley NJ, Neelakantan P, Gilbert G, Thomas BK, Graham RJ, Fujisawa T, Mills NL, Hildreth V, Prichard J, Kasim AS, Hancock HC, Plummer C
Publication type: Article
Publication status: Published
Journal: JACC: CardioOncology
Year: 2024
Pages: epub ahead of print
Online publication date: 27/08/2024
Acceptance date: 12/07/2024
Date deposited: 27/09/2024
ISSN (electronic): 2666-0873
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.jaccao.2024.07.010
DOI: 10.1016/j.jaccao.2024.07.010
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