Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma
David Austin, Rebecca Maier, Nasima Akhter, Mohammad Sayari, Emmanuel Ogundimu, Jamie Maddox, Sharareh Vahabi, Alison C. Humphreys, Janine Graham, Helen Oxenham, Sophie Haney, Nicola Cresti, Mark Verrill, Wendy Osborne, Kathryn L Wright, Rebecca Goranova, James R. Bailey, Nagesh Kalakonda, Mac Macheta, Mari F Kilner, Moya E. Young, Nick J. Morley, Pratap Neelakantan, Georgia Gilbert, Byju K Thomas, Richard Graham, Takeshi Fujisawa, Nicholas L. Mills, Victoria Hildreth, Jonathan Prichard, Adetayo Kasim, Helen Hancock, Chris Plummer
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: 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).