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?

Abstract

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 ␤-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 ␤-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 ␤-blockers, 8% of patients receiving

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Observational studies and small randomized clinical trials suggest a benefit in early initiation of angiotensin‐converting enzyme inhibitors and beta‐blockers for the prevention of cardiotoxicity 15, 89, 90, 91, 92, 93. The PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial tested whether angiotensin receptor blockers and/or beta‐blockers would be effective in preventing cardiotoxicity in patients diagnosed with breast cancer receiving anthracycline‐based chemotherapy with and without trastuzumab.…”

Cancer Therapy–Induced Cardiotoxicity: Basic Mechanisms and Potential Cardioprotective Therapies

“…There are nonrandomized data that suggest the combination of ACE inhibitors and carvedilol is beneficial for the recovery of LVEF in patients rechallenged with trastuzumab after initially experiencing cardiotoxicity with this agent . Furthermore, in a retrospective study of patients treated with trastuzumab, dual therapy with ACE inhibitors and β‐blockers was associated with LVEF recovery at 12 months . However, large, placebo‐controlled randomized clinical trials are warranted to determine the timing of initiation of these medications and the patients most likely to benefit from their use.…”

“…84 Furthermore, in a retrospective study of patients treated with trastuzumab, dual therapy with ACE inhibitors and b-blockers was associated with LVEF recovery at 12 months. 85 However, large, placebo-controlled randomized clinical trials are warranted to determine the timing of initiation of these medications and the patients most likely to benefit from their use. There are a number of studies under way investigating the utility of pharmacologic prophylaxis with b-blockers in the setting of trastuzumab use, including Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial 86 and NCT0100818 (www.clinicaltrials.gov).…”

Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection

“…In fact, most of the evidence comes from retrospective studies [78][79][80][81][82]. Compared to placebo, carvedilol seems to attenuate the LVEF decline and diastolic function impairment in patients treated with anthracyclines [81].…”