Can Bisoprolol Administration Prevent Anthracycline-induced Cardiotoxicity?: a Double-blind Randomized Trial.

This study was a double-blinded randomized control trial that was conducted at the Iran University of medical sciences.

Sixty-three patients that was diagnosed with non-metastatic breast cancer and anthracycline-based chemotherapy were planned for them were enrolled in this study. The exclusion criteria included: established ischemic heart disease, baseline LVEF <50%, cardiomyopathy (restrictive, dilated, or hypertrophic) detected by transthoracic echocardiography, moderate or severe valvular disease, prior chemotherapy, presence of contraindication for beta-blockers and cardiac arrhythmias and lack of patient compliance. Also, all the patients that had consumed angiotensin-converting enzyme Inhibitors, angiotensin receptor Inhibitors,diuretics, statins,other beta-blockers or non-dihydropyridin calcium channel blockers were excluded.Pateinets were randomly divided into two case and control groups by a box randomization method. At first, case group was comprised of 31 patients who were given bisoprolol at a dose of 1.25 mg daily, and in the absence of clinical symptoms and heart rate above 60 and systolic blood pressure above 100, 1.25 mg was added to the therapeutic dose every 2 weeks to reach 5 mg daily.

Two placebo tablets in similar shape and color to bisoprolol were given on a daily basis to each of the remaining 32 patients as the control group. Both bisoprolol and placebo administration was started since 7 days before start of chemotherapy and continued for 6 months.The study protocol was explained to each patient, and written consent was obtained from all patients.

chemotherapy regimen included doxorubicin (60 mg/m 2) and cyclophosphamide (600 mg/m2) followed by docetaxel (100 mg/m2) that was completed in four consecutive cycles, each cycle lasted 21 days and the cumulative dose of doxorubicin reached 240 mg/m2.

None of patients were treated with hormonal therapy or trastuzumab during the study period. Patients were visited by a cardiologist at baseline, before chemotherapy and every month after start of treatment. The presence of drug-related side effects (in particular hypotension and bradycardia) if any were recorded. The occurrence of heart failure, hospitalization and death were also collected.