Impact on clinical outcomes of renin-angiotensin system inhibitors against doxorubicin-related toxicity in patients with breast cancer and hypertension: A nationwide cohort study in South Korea

BACKGROUND: Although doxorubicin (DOX) is a commonly used potent chemotherapeutic agent in patients with breast cancer, its cardiotoxic effect is a concern, particularly in patients with hypertension. Antihypertensive renin-angiotensin system (RAS) inhibitors may potentially play a role in preventing overt heart failure (HF) due to DOX toxicity. This study aimed to evaluate whether the use of RAS inhibitors improves clinical outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy. METHODS: A total of 54,344 female patients who were first diagnosed with breast cancer and initiated into DOX therapy between 2008 and 2015 were recruited from a nationwide Korean cohort. Patients were divided into two groups: with and without hypertension (HT, n = 10,789; non-HT, n = 43,555), and the RAS inhibitor group (n = 1,728) was sub-classified from the HT group. Two propensity score-matched cohorts were constructed to compare the clinical outcomes between non-HT and HT groups and between non-HT and RAS inhibitor groups. The primary outcome was the composite of HF and death. RESULTS: After propensity score matching, the HT group had a higher risk for HF (adjusted hazard ratio [HR] = 1.30, 95% confidence intervals [95% CI] = 1.09-1.55) compared to the non-HT group, but there was no significant difference in primary outcome between the two groups. The RAS inhibitor group had a lower risk for primary outcome (adjusted HR = 0.78, 95% CI = 0.65-0.94) and death (adjusted HR = 0.81, 95% CI = 0.66-0.99) compared to the non-HT group. CONCLUSIONS: Hypertension is a risk factor for HF in patients with breast cancer undergoing DOX chemotherapy. However, the RAS inhibitors used to treat hypertension may contribute to decreased mortality and improved clinical outcomes.