A biomarker-guided approach to cardioprotection in cancer patients receiving anthracyclines is associated with improvements in left ventricular ejection fraction

1. An N-terminal pro–B-type natriuretic peptide (NT-proBNP)-guided approach to neurohormonal therapy for cardioprotection in patients receiving anthracyclines for breast cancer or lymphoma is safe, feasible, and associated with early improvement in left ventricular ejection fraction (LVEF).

Evidence Rating Level: 2 (Good)

Study Rundown: Anthracyclines are a class of chemotherapy drugs used to treat a wide variety of cancers, including leukemias, lymphomas, and solid tumours such as breast, ovarian, and lung cancers. However, cardiotoxicity is a serious, dose-dependent side-effect that can lead to treatment interruptions and worse overall survival. Existing studies have evaluated the efficacy of neurohormonal antagonists for cardioprotection but shown mixed results, likely due to a “one size fits all” approach that includes low-risk populations. Therefore, there is a need for a risk-guided cardioprotection approach to identify patients at higher cardiovascular risk who may benefit from intervention.

This prospective, multicenter, open-label, randomized clinical trial was conducted across multiple sites at the University of Pennsylvania Health System from March 18, 2021, to October 20, 2023. Participants included patients aged 18 years or older with a diagnosis of breast cancer or lymphoma and planning for anthracycline-based chemotherapy. Patients randomized to the NT-proBNP-guided arm had NT-proBNP concentrations measured and subsequent initiation/titration of neurohormonal therapy as determined by a predefined treatment algorithm. Patients randomized to the usual care arm received routine clinical care, and NT-proBNP concentrations were not measured.

Overall, this study found that patients in the NT-proBNP arm had a significantly higher LVEF at 3 months. However, the difference diminished over time and was not significant by the end of the study period (12 months). There were no significant differences in the incidence of adverse events. An NT-proBNP-guided cardioprotection strategy was safe and was associated with early improvement in LVEF. Future studies are required to further elucidate the risks and benefits of an NT-proBNP-guided approach to cardioprotection in patients receiving anthracyclines for cancer. 

Click here to read this study in JAMA Network Open

Relevant reading: Efficacy of Neurohormonal Therapies in Preventing Cardiotoxicity in Patients With Cancer Undergoing Chemotherapy

In-Depth [randomized clinical trial]:

Current studies intended to provide cardioprotection for patients receiving anthracyclines for cancer have delivered mixed results, likely due to the absence of specific, risk-directed guidelines. This randomized clinical trial investigated the efficacy and safety of an NT-proBNP-guided approach to neurohormonal therapy. The primary outcomes were the feasibility and safety of this approach.

100 patients were randomized in a 1:1 ratio to the NT-proBNP-guided (mean [SD] age = 54.5 (12.5); 84.0% female)  and usual care arms (mean [SD] age = 50.0 (15.9); 88.0% female). At 12 months, participants in the NT-proBNP–guided arm were more likely to be taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (19 of 47 [40.4%] vs 2 of 42 [4.8%]; P < .001) and β-blockers (11 of 47 [23.4%] vs 3 of 42 [7.1%]; P = .04), compared with participants in the usual care arm. There was no significant difference in the incidence of adverse events, including acute kidney injury, bradycardia, chest pain, cough, dyspnea, fatigue, and headache. At 3 months, LVEF was slightly greater in the NT-proBNP–guided arm compared with the usual care arm (mean difference, 2.0% [95% CI, 0.5%-3.5%]; P = .007). However, there was a nonsignificant difference (P=0.18) at 12 months. There was no significant difference in any other echocardiographic measurement.

Image: PD

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