title: Prevention of chemotherapy-induced left ventricular dysfunction with enalapril and carvedilol: rationale and design of the OVERCOME trial.
abstract: BACKGROUND
  The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents, including high-dose myeloablative regimens used in autologous hematopoietic stem cell transplantation (HSCT). Many of these treatments could induce left ventricular dysfunction (LVD), and limit their efficacy. Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infarction, and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity.
  
  
  METHODS
  This is a prevention, parallel-assignment, randomized, controlled, clinical efficacy study. Ninety patients recently diagnosed of acute leukemia or undergoing autologous HSCT and with normal LV ejection fraction will be randomized to enalapril and carvedilol or to the control group. Echocardiogram and a cardiac magnetic resonance imaging studies will be performed at baseline and 6-9 months after randomization. The primary efficacy endpoint is the change from baseline in LV ejection fraction. Secondary endpoints include the assessment of LV volumes and diastolic function, and the incidence of death, heart failure, or LVD.
  
  
  CONCLUSIONS
  The OVERCOME study will be the first clinical trial to test the preventive efficacy on LVD of combined treatment with enalapril and carvedilol administered to patients with hematologic malignancies submitted to current treatment with intensive chemotherapy.
authors.affiliation: Cardiology Department, Thorax Institute, Hospital Clinic, Barcelona, Spain. xbosch@clinic.ub.es
authors.forename: Xavier
authors.initials: X
authors.lastname: Bosch
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Marta
authors.initials: M
authors.lastname: Sitges
authors.forename: Teresa M
authors.initials: TM
authors.lastname: de Caralt
authors.forename: Ariadna
authors.initials: A
authors.lastname: Domènech
authors.forename: José T
authors.initials: JT
authors.lastname: Ortiz
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzó
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales-Ruiz
authors.forename: Rosario J
authors.initials: RJ
authors.lastname: Perea
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D018401:Sample Size; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004656:Enalapril