title: Cardioprotective Effects of Carvedilol in Inhibiting Doxorubicin-induced Cardiotoxicity.
abstract: OBJECTIVE
  Anthracyclines (ANTs) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer. We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity.
  
  
  METHODS
  In this randomized, single-blind, placebo-controlled study, 91 women with recently diagnosed breast cancer undergoing ANT therapy were randomly assigned to groups treated with either carvedilol (n = 46) or placebo (n = 45). Echocardiography was performed before and at 6 months after randomization, and absolute changes in the mean left ventricular ejection fraction, left ventricular end diastolic volume, and left ventricular end systolic volume were determined. Furthermore, the percentage change in the left atrial (LA) diameter and other variables of left ventricular (LV) diastolic function, such as transmitral Doppler parameters, including early (E wave) and late (A wave) diastolic velocities, E/A ratio and E wave deceleration time, pulmonary venous Doppler signals, including forward systolic (S wave) and diastolic (D wave) velocities into LA, late diastolic atrial reversal velocity, and early diastolic tissue Doppler mitral annular velocity (e') were measured. In addition, tissue Doppler mitral annular systolic (s') velocity, as a marker of early stage of LV systolic dysfunction, E/e' ratio, as a determinant of LV filling pressure, and troponin I level, as a marker of myocardial necrosis were measured.
  
  
  RESULTS
  At the end of follow-up period, left ventricular ejection fraction did not change in the carvedilol group. However, this parameter was significantly reduced in the control group (P < 0.001). Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group. In pulse Doppler studies, pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group. Moreover, a significant decrease in the mitral annuli early diastolic (e') and peak systolic (s') velocities and a significant increase in the E (the peak early diastolic velocity)/e' ratio in the control group were also observed. However, none of these variables were adversely changed at the end of follow-up in the carvedilol group. Furthermore, the TnI level was significantly higher in the control group than in the carvedilol group (P = 0.036) at 30 days after the initiation of chemotherapy.
  
  
  CONCLUSIONS
  Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity, even at low doses.
authors.affiliation: *Department of Cardiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; †Department of Hematology, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran; ‡Student Research Committee, Cardiovascular Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; §Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran; and ¶Department of Biostatics, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nabati
authors.forename: Ghasem
authors.initials: G
authors.lastname: Janbabai
authors.forename: Saideh
authors.initials: S
authors.lastname: Baghyari
authors.forename: Khadige
authors.initials: K
authors.lastname: Esmaili
authors.forename: Jamshid
authors.initials: J
authors.lastname: Yazdani
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D016279:Atrial Function, Left / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy*; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D066126:Cardiotoxicity; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007492:Iran; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D002227:Carbazoles; D002317:Cardiovascular Agents; D011412:Propanolamines; D019210:Troponin I; D000077261:Carvedilol