Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial
Mônica Samuel Avila, Silvia Moreira Ayub-Ferreira, Mauro Rogerio de Barros Wanderley Jr, Fatima das Dores Cruz, Sara Michelly Gonçalves Brandão, Vagner Oliveira Carvalho Rigaud, Marília Harumi Higuchi-Dos-Santos, Ludhmila Abrahão Hajjar, Roberto Kalil Filho, Paulo Marcelo Hoff, Marina Sahade, Marcela S M Ferrari, Romulo Leopoldo de Paula Costa, Max Senna Mano, Cecilia Beatriz Bittencourt Viana Cruz, Maria Cristina Abduch, Marco Stephan Lofrano Alves, Guilherme Veiga Guimaraes, Victor Sarli Issa, Marcio Sommer Bittencourt, Edimar Alcides Bocchi, Mônica Samuel Avila, Silvia Moreira Ayub-Ferreira, Mauro Rogerio de Barros Wanderley Jr, Fatima das Dores Cruz, Sara Michelly Gonçalves Brandão, Vagner Oliveira Carvalho Rigaud, Marília Harumi Higuchi-Dos-Santos, Ludhmila Abrahão Hajjar, Roberto Kalil Filho, Paulo Marcelo Hoff, Marina Sahade, Marcela S M Ferrari, Romulo Leopoldo de Paula Costa, Max Senna Mano, Cecilia Beatriz Bittencourt Viana Cruz, Maria Cristina Abduch, Marco Stephan Lofrano Alves, Guilherme Veiga Guimaraes, Victor Sarli Issa, Marcio Sommer Bittencourt, Edimar Alcides Bocchi
Abstract
Background: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial.
Objectives: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity.
Methods: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction.
Results: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057).
Conclusions: In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).
Keywords: cardiomyopathy; chemotherapy; prevention; troponin; β-blockers.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed