Elsevier

The American Journal of Cardiology

Volume 188, 1 February 2023, Pages 68-79
The American Journal of Cardiology

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

https://doi.org/10.1016/j.amjcard.2022.11.006Get rights and content

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.

Section snippets

Methods

This study was approved by the institutional review board. This was a single-center, retrospective cohort study of patients diagnosed with breast cancer from January 2014 to December 2021. Patients were included in the study if they had received a diagnosis of breast cancer, received treatment for their cancer with anthracycline and/or trastuzumab, and had an echocardiogram performed before and after treatment initiation. Patients were excluded from the study if they did not receive treatment

Results

Over the study period, 937 patients were screened and 459 met the inclusion criteria. Baseline characteristics are shown in Table 1. The average age of all participants was 55 years (SD ± 12). A total of 375 were White (82%), 51 were Black (11%), and 33 were self-reported as “Other” (7%) for their racial background. All patients were women and 113 had triple negative breast cancer (25%). A total of 239 were treated with only trastuzumab (52%), 158 with only anthracycline (34%) and 62 were

Discussion

The principal finding of our study showed no association between previous neurohormonal antagonist use and development of cardiotoxicity. This finding remained consistent even after matching for relevant baseline characteristics. The time-to-event analysis failed to show significant differences between treatment and nontreatment groups; a finding that also persisted after matching. Secondarily, increased age was a notable risk factor and emphasizes the importance of screening for asymptomatic

Disclosures

The authors have no conflicts of interest to declare.

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