In an interim analysis of the Italian phase III SAFE trial reported in JAMA Oncology, Livi et al found that a cardioprotective strategy using ramipril and/or bisoprolol reduced the risk of myocardial dysfunction in women with nonmetastatic breast cancer receiving anthracycline-based chemotherapy.
Study Details
The interim analysis was performed after the first 174 eligible women were enrolled in the double-blind multicenter trial. Patients with no diagnosis of cardiovascular disease who were to receive primary or postoperative anthracycline-based chemotherapy were randomly assigned 1:1:1:1 between July 2015 and June 2020 to receive placebo (n = 42), ramipril at a target dose of 5 mg once daily (n = 43), bisoprolol at a target dose of 5 mg once daily (n = 45), or ramipril and bisoprolol (n = 43). Treatment was given for 1 year from initiation of chemotherapy or until the end of trastuzumab therapy in HER2-positive patients.
The primary endpoint was defined as detection of any subclinical impairment (worsening ≥ 10%) in myocardial function and deformation measured with standard and three-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain. Findings at 12 months are reported.
Key Findings
At 12 months, 3D-LVEF worsened by 4.4% in the placebo group vs 3.0%, 1.9%, and 1.3% in the ramipril, bisoprolol, and ramipril/bisoprolol groups, respectively (overall P = .01).
The interim analysis of this randomized clinical trial suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy–related LVEF decline and heart remodeling.— Livi et al
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Global longitudinal strain worsened by 6.0% in the placebo group; worsened by 1.5% and 0.6% in the ramipril and bisoprolol groups, respectively; and improved by 0.1% in the ramipril/bisoprolol group (overall P < .001).
Total patients with a reduction of ≥ 10% in 3D-LVEF were eight (19%) in the placebo group, five (11.5%) in the ramipril group, five (11.4%) in the bisoprolol group, and three (6.8%) in the ramipril/bisoprolol group. Global longitudinal strain worsening of ≥ 10% was observed in 15 patients (35.7%) in the placebo group, 7 (15.9%) in the ramipril group, 6 (13.6%) in the bisoprolol group, and 6 (13.6%) in the ramipril/bisoprolol group (overall P = .03).
Patients in the ramipril/bisoprolol group were more likely to have dose reduction (18.6%) and had higher rates of hypotension (14%) and cough (4.7%) compared with the other groups (all P < .05).
The investigators concluded, “The interim analysis of this randomized clinical trial suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy–related LVEF decline and heart remodeling.”
Icro Meattini, MD, of the Department of Experimental and Clinical Biomedical Sciences, University of Florence, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
