Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
Condition: Cardiomyopathies; Chemotherapy Effect; Diastolic Dysfunction; Systolic Dysfunction
MeSH terms: Cardiomyopathies; Cardiotoxicity
Study type: Interventional
Phase: Phase 3

Summary: 
      Anthracyclines are one of the most well-known and effective drugs used to treat
      malignancies.The most important limiting factor in the use of this drug is its cardiac
      toxicity which includes cardiomyopathy and congestive heart failure. Bisoprlol is a
      β1-specific β-blocker that can reduce cardiac overload and also have anti-inflammatory
      antioxidant effects and can reduce reactive oxygen metabolites so it can be used as a
      cardioprotective agent in patients with a high risk of heart failure. To the best of our
      knowledge, no study has been performed to evaluate the prophylactic effect of bisoprolol
      solely in patients under chemotherapy with anthracyclines. This study is aimed to evaluate
      the cardioprotective role of bisoprolol in patients with non-metastatic breast cancer
      receiving doxorubicin, by measuring global longitudinal strain before and after treatment.
    

Detailed description: 
      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.

      Transthoracic echocardiography was performed 1 week prior to the chemotherapy and 1 week
      after the fourth doxorubicin cycle. Strain, strain-rate parameters and LVEF wereevaluated. A
      decrease of more than 10-50% in LVEF was considered as a criterion for discontinuing
      chemotherapy with anthracycline and patients were excluded from the study.

      Blind conventional 2D echocardiography done using an EPIQ 7 premium ultrasound system
      (Philips Healthcare, Stockholm, Sweden) equipped with a 2.5-MHz transducer. All measurements
      were performed following the recommendations of the American Society of Echocardiography
      (21)in apical (2- and 4-chamber and apical long axis) and parasternal (long and short axis)
      views and measured at the time of acquisition without reference to previous measurements.
      Images was digitally stored for off-line Speckle-tracking analysis (EchoPAC 108.1.5,
      GE-Vingmed). Longitudinal strain, evaluating the shortening (negative strain) and lengthening
      (positive strain) of the myocardial wall, was measured from the three apical views (long-axis
      and two- and four-chamber views): GLS was calculated by averaging the peak strain values of
      18 segments. The mean frame rate of 2D images was 90 ±4 frames/s.

      SPSS version 18.0 (SPSS, Inc., Chicago, IL) was used for statistical analysis. All
      quantitative data have been expressed as mean ± SD.Categorical variables were summarized as
      number(percent), and continuous variables as either median (range) or mean ± standard
      deviation. Independent-sample t-tests were used to compare LVEF, strain and strain-rate
      parameters between the two groups before and after the intervention. Paired sample t-tests
      were used to compare the echocardiography findings in each group before and after the
      chemotherapy. P-values less than 0.05 were considered to be statistically significant.
    

Intervention name(s): Bisoprolol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): For patients who were candidates to start therapy with anthracycline, bisoprolol was administrated as explained before to determine the effect of this drug on the reduction of anthracycline-induced cardiomyopathy.; Tablets with similar shape and size and color to bisoprolol were given to the patients whom undergone chemotherapy with anthracyclines to compare the effects between two groups.
Intervention MeSH terms: Bisoprolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: Bisoprolol; Cardiomyopathy; Chemotherapy; Anthracyclines