Author + information
- Received February 16, 2018
- Revision received February 28, 2018
- Accepted February 28, 2018
- Published online March 11, 2018.
- Monica Samuel Avila, MDa,
- Silvia Moreira Ayub-Ferreira, MD, PhDa,
- Mauro Rogerio de Barros Wanderley Junior, MDa,
- Fatima das Dores Cruz, RNa,
- Sara Michelly Gonçalves Brandão, RNa,
- Vagner Oliveira Carvalho Rigaud, PhDa,
- Marilia Higushi-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, Brazil
- bHeart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
- cInstituto do Câncer do Estado de São Paulo-USP, Brazil
- dCenter for Clinical and Epidemiological Research, University Hospital, University of São Paulo, São Paulo, Brazil
- ↵∗Address for correspondence: Edimar Alcides Bocchi, MD, PhD R. Dr. Eneas de Carvalho Aguiar 44 São Paulo Brazil, 05403900 Telephone and Fax: +551126615419, Twitter @monicaAGrinberg.
Background Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial.
Objective The aim of this prospective, randomized, double-blind, placebo-controlled study was to evaluate the role of carvedilol in preventing ANT cardiotoxicity.
Methods We 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 (TnI), BNP, and diastolic dysfunction.
Results Primary endpoint occurred in 14 (14.5%) in the carvedilol group and 13 (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or BNP were noted between groups. A significant difference existed between groups in TnI 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 follow-up was noted in the carvedilol group (44.1±3.64 to 45.2±3.2 vs 44.9±3.6 to 46.4±4.0 mm, p = 0.057).
Conclusion In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage, we noted a 13.5 –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. (NCT01724450).
Clinical Trial ClinicalTrials.gov Identifier NCT01724450
Drs. Monica Samuel Avila and Silvia Moreira Ayub-Ferreira contributed equally to this article.
Disclosure: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2010/18078-8) as part of Monica Samuel Avila’s doctoral thesis under the guidance of Silvia Moreira Ayub-Ferreira. None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the present manuscript.
Consideration Of Private Enterprise: Baldacci Laboratories S.A. donated the carvedilol and placebo used in this study. The Baldacci Laboratories did not participate in any phase of the study.
- Received February 16, 2018.
- Revision received February 28, 2018.
- Accepted February 28, 2018.
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