Administration of angiotensin-converting enzyme inhibitors and β-blockers during adjuvant trastuzumab chemotherapy for nonmetastatic breast cancer: marker of risk or cardioprotection in the real world?

BACKGROUND: Adjuvant trastuzumab therapy improves the outcome of patients with early breast cancer (EBC) and overexpression of human epidermal growth factor receptor 2 (HER2). However, it is potentially cardiotoxic. This study aims to evaluate the relationship between the use of angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARBs) and/or β-blockers and development of heart failure (HF) and/or left ventricular dysfunction during 1 year of adjuvant trastuzumab therapy.

METHODS: A total of 499 women receiving adjuvant trastuzumab therapy for EBC entered in a multicenter registry and were divided into four subgroups according to treatment with ACEi/ARBs and/or β-blockers. Occurrence of HF and decrease of left ventricular ejection fraction (LVEF; minimum 10 percentage points) were recorded.

RESULTS: HF occurred in 2% of patients who did not take either ACEi/ARBs or β-blockers, 8% of patients receiving ACEi/ARBs alone, 8% receiving β-blockers alone (p = .03), and 19% receiving both medications (p < .01). The prevalence of patients with LVEF that decreased by at least 10 percentage points was similar in all groups. Combined ACEi/ARBs and β-blocker therapy was independently associated with hypertension and a significant reduction of LVEF from baseline to 3-month evaluation. The use of ACEi/ARBs alone or β-blockers alone was predicted only by hypertension. Combined therapy of ACEi/ARBs plus β-blockers predicted LVEF recovery from the 3-month to 12-month evaluation.

CONCLUSIONS: In clinical practice, the degree of hypertension and decrease in LVEF during the first 3 months of adjuvant trastuzumab therapy for EBC are associated with the use of ACEi/ARBs and β-blockers. The combined use of these two medications is associated with a recovery of LVEF during months 3-12 of adjuvant trastuzumab therapy.