title: Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies).
abstract: OBJECTIVE
  This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies.
  
  
  BACKGROUND
  Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy.
  
  
  METHODS
  In this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD were randomly assigned to a group receiving enalapril and carvedilol (n = 45) or to a control group (n = 45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction (LVEF).
  
  
  RESULTS
  The mean age of patients was 50 ± 13 years old, and 43% were women. At 6 months, LVEF did not change in the intervention group but significantly decreased in controls, resulting in a -3.1% absolute difference by echocardiography (p = 0.035) and -3.4% (p = 0.09) in the 59 patients who underwent CMR. The corresponding absolute difference (95% confidence interval [CI]) in LVEF was -6.38% (95% CI: -11.9 to -0.9) in patients with acute leukemia and -1.0% (95% CI: -4.5 to 2.5) in patients undergoing autologous HSCT (p = 0.08 for interaction between treatment effect and disease category). Compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF <45% (6.7% vs. 24.4%, p = 0.02).
  
  
  CONCLUSIONS
  Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy. The clinical relevance of this strategy should be confirmed in larger studies. (Prevention of Left Ventricular Dysfunction During Chemotherapy [OVERCOME]; NCT01110824).
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: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.forename: Marta
authors.initials: M
authors.lastname: Sitges
authors.forename: Ariadna
authors.initials: A
authors.lastname: Domènech
authors.forename: José T
authors.initials: JT
authors.lastname: Ortiz-Pérez
authors.forename: Teresa M
authors.initials: TM
authors.lastname: de Caralt
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales-Ruiz
authors.forename: Rosario J
authors.initials: RJ
authors.lastname: Perea
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzó
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004656:Enalapril