Association of Neurohormonal Antagonists on Incident Cardiotoxicity in Patients With Breast Cancer

Cardiovascular disease is the leading cause of mortality among breast cancer survivors. Anthracyclines and trastuzumab have been associated with an increased risk of cardiotoxicity, requiring close follow-up for signs of clinical heart failure or asymptomatic left ventricular systolic dysfunction. Whether neurohormonal antagonism with angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor blockers (ARBs), or β-blockers can prevent the development of chemotherapy-induced cardiomyopathy in this population remains unknown. We studied 459 women who were diagnosed with breast cancer at our medical center from January 2014 to December 2021 and evaluated baseline characteristics, oncologic treatment, and outcomes. The primary end point was the development of cardiotoxicity, defined as symptomatic decline in ejection fraction of ≥5% below 55% or an asymptomatic decline of ≥10% after treatment with chemotherapy. Patients who were exposed to neurohormonal antagonists were more likely to have hypertension, hyperlipidemia, and diabetes. There was an increased risk of cardiotoxicity noted for patients who were older (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.01 to 1.1), smokers within the past 10 years (HR 2.54, 95% CI 1.41 to 4.6), or who received a combination of both trastuzumab and anthracycline therapy (HR 2.52, 95% CI 1.01 to 6.3). Over a median follow-up of 12 months, there were no significant protective benefits noted for patients who were taking ACE-I/ARBs (HR 0.49, 95% CI 0.17 to 1.4), β-blockers (HR 0.50, 95% CI 0.16 to 1.6), or both (HR 1.30, 95% CI 0.44 to 3.9). In conclusion, previous use of ACE-I/ARBs and β-blockers, separately or in combination, was not associated with a reduction in the development of cardiotoxicity in patients receiving anthracycline or trastuzumab therapies. Older age, smoking, and combination chemotherapy were found to be associated with an increased risk.