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 beta-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 beta-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 beta-blockers, 8% of patients receiving ACEi/ARBs alone, 8% receiving beta-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 beta-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 beta-blockers alone was predicted only by hypertension. Combined therapy of ACEi/ARBs plus beta-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 beta-blockers. The combined use of these two medications is associated with a recovery of LVEF during months 3-12 of adjuvant trastuzumab therapy. The Oncologist 2012;17:917-924