The Role of Lisinopril and Bisoprolol to Prevent Anthracycline Induced Cardiotoxicity in Locally Advanced Breast Cancer Patients

BACKGROUND: Anthracyclines are a class of chemotherapeutic agents that are used to treat many different cancers, including breast cancer. Although anthracyclines remain an effective and commonly used therapy, their use is limited by cardiotoxicity. Heart failure and left ventricular (LV) dysfunction are the short and long-term complications of anthracyline exposure occurring in 5% to 23% of patients. Recent prospective studies have investigated the prophylactic role of ACE inhibitors and beta-blockers as cardioprotective agents. This study aimed to evaluate whether the addition of lisinopril and bisoprolol could prevent anthracycline induced cardiotoxicity. METHODS: In this randomized, controlled trial, 74 subjects with locally advanced breast cancer were randomly assigned to a group receiving lisinopril and bisoprolol (n=37) or to a control group (n=37). Lisinopril and bisoprolol was started simultaneously 24 h before the first cycle of chemotherapy. The initial dose was 2.5 mg each, once daily, and was increased gradually under close supervision to 10 mg if SBP persistently remained >90 mmHg and HR >60 bpm. Echocardiographic studies were performed before and after the 6th cycle of neoadjuvant anthracycline-based chemotherapy (FAC). The primary endpoint was the change from baseline LVEF. RESULTS: There was no difference in baseline LVEF between intervention and control group (65.77 ± 4.56 % v 65.64 ± 455 %, p = 0.92). There was also no difference in total anthracycline doses between 2 groups (579.48 ± 65.10 mg vs 557.50 ± 47.76 mg, p = 0.18). However, after 6 cycles of FAC, the rate of decline in LVEF was greater in control group (-5.52 ± 8,90 %) than in the intervention group (-0.27 ± 5.73 %) with p = 0.017. No severe adverse effects occurred in the intervention group related to the treatment with lisinopril and bisoprolol. CONCLUSION: Combined treatment with lisinopril and bisoprolol may prevent anthracycline-induced cardiotoxicity in patients with locally advanced breast cancer treated with anthracycline-based chemotherapy. The clinical relevance of this study should be confirmed in larger studies with longer follow up time.