Author + information
- Received February 16, 2018
- Revision received February 28, 2018
- Accepted February 28, 2018
- Published online May 14, 2018.
- Mônica Samuel Avila, MDa,∗,
- Silvia Moreira Ayub-Ferreira, MD, PhDa,∗,
- Mauro Rogerio de Barros Wanderley Jr., MDa,
- Fatima das Dores Cruz, RNa,
- Sara Michelly Gonçalves Brandão, RNa,
- Vagner Oliveira Carvalho Rigaud, PhDa,
- Marília Harumi Higuchi-dos-Santos, MD, PhDc,
- Ludhmila Abrahão Hajjar, MD, PhDb,c,
- Roberto Kalil Filho, MD, PhDb,c,
- Paulo Marcelo Hoff, MD, PhDc,
- Marina Sahade, MDc,
- Marcela S.M. Ferrari, MDc,
- Romulo Leopoldo de Paula Costa, MDc,
- Max Senna Mano, MD, PhDc,
- Cecilia Beatriz Bittencourt Viana Cruz, MDb,c,
- Maria Cristina Abduch, VMDb,
- Marco Stephan Lofrano Alves, MD, PhDb,
- Guilherme Veiga Guimaraes, PhDa,
- Victor Sarli Issa, MD, PhDa,
- Marcio Sommer Bittencourt, MD, MPH, PhDb,c,d and
- Edimar Alcides Bocchi, MD, PhDa,∗ ()
- aHeart Failure Department, Heart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- bHeart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- cInstituto do Câncer do Estado de São Paulo-Universidade de São Paulo, São Paulo, Brazil
- dCenter for Clinical and Epidemiological Research, University Hospital, University of São Paulo, São Paulo, Brazil
- ↵∗Address for correspondence:
Dr. Edimar Alcides Bocchi, Heart Failure Department, Heart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, R. Dr. Eneas de Carvalho Aguiar 44, São Paulo 05403900, Brazil.
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)
↵∗ Drs. Avila and Ayub-Ferreira contributed equally to this article and are joint first authors.
This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2010/18078-8) as part of Mônica Samuel Avila’s doctoral thesis under the guidance of Silvia Moreira Ayub-Ferreira. Baldacci Laboratories donated the carvedilol and placebo used in this study. The Baldacci Laboratories did not participate in any phase of the study. Dr. Issa has received speaking honoraria from Novartis. Dr. M. Bittencourt has received unrestricted funding support from Sanofi; and speaking honoraria from Boston Scientific. Dr. Bocchi has received consulting fees from Servier and AstraZeneca; subsidized travel/hotel/registration fees and other honoraria from Servier; serves on steering committees for Servier and Novartis; and is a contracted researcher for Jansen and Bayer/Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 16, 2018.
- Revision received February 28, 2018.
- Accepted February 28, 2018.
- 2018 American College of Cardiology Foundation