Abstract

Introduction and Hypothesis: Female sex has long been considered a risk factor for anthracycline-associated cardiotoxicity, based largely on data in childhood cancer survivors. However, preclinical experiments suggest that female sex hormones present in adulthood may protect against doxorubicin cardiotoxicity. We therefore hypothesized that female sex would be associated with a decreased odds of heart failure in adult patients treated with anthracyclines. Methods: We conducted a retrospective cohort study of 871 adult patients (44% women and 56% men) at our medical center with no prior history of heart failure who were treated with anthracyclines for non-hormone-dependent malignancies including lymphoma, leukemia, and sarcoma. Patients who expired during the study period were excluded. The presence or absence of heart failure within five years of initiation of anthracyclines was assessed using ICD-9/10 codes. Logistic regression models were used to assess odds ratios based on self-reported sex and other covariates, adjusting for age. Results: Baseline characteristics were similar in men and women, including age, total cumulative anthracycline dose, and prevalence of cardiovascular comorbidities such as hypertension, diabetes, and coronary artery disease. The odds of heart failure increased modestly with age (OR: 1.02; 95% CI: 1.01 to 1.03, p = 0.001). In an age-adjusted model, female sex was not associated with subsequent heart failure (OR: 1.03, 95% CI 0.72 to 1.47, p = 0.88), including after stratification by age ≤ 50 years or > 50 years as a surrogate for menopausal status. Conclusions: In this retrospective cohort study, female sex was not associated with heart failure in adult patients treated with anthracyclines for non-hormone-dependent tumors. These findings diverge from prior reports suggesting an increased risk of cardiotoxicity in women. Future studies will assess the competing risks of cancer and cardiovascular disease/death in men versus women treated with anthracyclines.

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