TOPLINE:

In a multicentre trial, sacubitril-valsartan did not significantly prevent the anthracycline- and trastuzumab-related decline in left ventricular ejection fraction during breast cancer treatment. However, this combination prevented the decline in the echocardiographic global longitudinal strain and reduced chronic myocardial injury and stress.

METHODOLOGY:

• Researchers conducted a randomised, parallel-group, placebo-controlled trial (PRADA II) including 138 adult women with early breast cancer scheduled for (neo)adjuvant chemotherapy with epirubicin and cyclophosphamide between January 2019 and January 2023.
• Participants were randomly assigned to receive either sacubitril-valsartan (n = 69; mean age, 53.6 years; 97.1% European) or matching placebo (n = 69; mean age, 54.5 years; 98.6% European) prior to the initiation of anthracycline therapy.
• The primary outcome was the change in left ventricular ejection fraction, assessed using cardiovascular magnetic resonance from randomisation to 18 months.
• Secondary outcomes included changes in echocardiographic global longitudinal strain and circulating concentrations of cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to 18 months.

TAKEAWAY:

• Left ventricular ejection fraction on cardiovascular magnetic resonance declined by 2.2 percentage points with placebo vs 1.1 percentage points with sacubitril-valsartan from baseline to 18 months, with a non-significant between-group difference of 1.1 percentage points (95% CI, -0.4 to 2.7; P = .16).
• Left ventricular global longitudinal strain remained stable in the sacubitril-valsartan group but declined progressively in the placebo group (between-group difference, -0.85; 95% CI, -1.52 to -0.18).
• From baseline to 18 months, increases in concentrations of NT-proBNP and cardiac troponin I were lower with sacubitril-valsartan than with placebo (between-group difference, -0.53 [95% CI, -0.95 to -0.11] and -0.30 [95% CI, -0.55 to -0.055], respectively); however, concentrations of cardiac troponin T did not differ between the two groups.
• Overall, 29 serious adverse events were reported: 13 in the sacubitril-valsartan group with no deaths and 16 in the placebo group with one death.

IN PRACTICE:

"In conclusion, adjuvant treatment for early breast cancer is associated with a reduction in left ventricular ejection fraction that was not significantly attenuated by sacubitril-valsartan," the authors wrote.

SOURCE:

This study was led by Torbjørn Omland, MD, PhD, MPH, K.G. Jebsen Centre for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. It was published online on August 29, 2025, in Circulation.

LIMITATIONS:

This study had limited statistical power to detect differences in categorical endpoints, including clinical events. The placebo-controlled trial design prevented the evaluation of whether treatment effects were due to sacubitril or valsartan specifically. Additionally, the study population was generally at low-to-moderate cardiovascular risk and ethnically homogeneous, potentially limiting the generalisability of the findings.

DISCLOSURES:

The trial received funding from the National Programme for Clinical Therapy Research in the Specialist Health Services, Norwegian Cancer Society, South-Eastern Norway Regional Health Authority, and University of Oslo. Two authors were supported by a grant from the Kristian Gerhard Jebsen Foundation. Some authors reported receiving speaker or consulting honoraria or having other ties with various pharma companies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.