Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in low-risk breast cancer women: results of a prospective randomized study

BACKGROUND: Anthracyclineinduced cardiotoxicity (AIC) remains the main longterm irreversible side effect in malignancy survivors. Cardiotoxicity prevention is one of the most reasonable approaches. AIMS: In this prospective randomized openlabel study, we aimed to verify whether ramipril protects from earlyonset AIC in women with breast cancer (BC). METHODS: We analyzed data from 96 women (median age, 47 years) with BC after breast surgery, without significant cardiovascular diseases, who were eligible for adjuvant anthracyclines. They were randomized to a ramipril or control arm. Cardiotoxicity was estimated with repeat echocardiography and themeasurement of troponin I and Nterminal fragment of the prohormone brain natriuretic peptide (NTproBNP) levels over 1year followup. Anthracyclineinduced cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF), elevated biomarker levels, and/or occurrence of heart failure (HF) or cardiac death. RESULTS: A decrease in LVEF above 10percent points occurred in 6.3% of ramipril patients and 18.5% ofcontrols (P = 0.15). No cases of HF, cardiac death, or LVEF decline below 50% were reported. The percentage of patients with elevated NTproBNP levels increased with time in controls (P = 0.003) and remained unchanged in the ramipril arm. At the end of followup, an increase in NTproBNP levels was more common and decline was less common in the control than ramipril arm (P = 0.01). No significant differences in troponin levels were found between the study arms. Ramipril was well tolerated in normotensive women. CONCLUSIONS: In relatively young women with BC without serious comorbidities, who received anthracyclines, 1year treatment with ramipril exerts potentially protective effects on cardiotoxicity assessed with NTproBNP levels.