Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity

Author(s):Show less -

Avila, Monica Samuel ^[1] ; Ayub-Ferreira, Silvia Moreira ^[1] ; de Barros Wanderley, Jr., Mauro Rogerio ^[1] ; Cruz, Fatima das Dores ^[1] ; Goncalves Brandao, Sara Michelly ^[1] ; Carvalho Rigaud, Vagner Oliveira ^[1] ; Higuchi-dos-Santos, Marilia Harumi ^[2] ; Hajjar, Ludhmila Abrahao ^{[2, 3]} ; Kalil Filho, Roberto ^{[2, 3]} ; Hoff, Paulo Marcelo ^[2] ; Sahade, Marina ^[2] ; Ferrari, Marcela S. M. ^[2] ; de Paula Costa, Romulo Leopoldo ^[2] ; Mano, Max Senna ^[2] ; Bittencourt Viana Cruz, Cecilia Beatriz ^[2] ; Abduch, Maria Cristina ^[3] ; Lofrano Alves, Marco Stephan ^[3] ; Guimaraes, Guilherme Veiga ^[1] ; Issa, Victor Sarli ^[1] ; Bittencourt, Marcio Sommer ^{[4, 2, 3]} ; Bocchi, Edimar Alcides ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Heart Failure Dept, Heart Inst InCor, R Dr Eneas de Carvalho Aguiar 44, BR-05403900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Heart Inst InCor, Fac Med, Hosp Clin, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Univ Hosp, Ctr Clin & Epidemiol Res, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of the American College of Cardiology; v. 71, n. 20, p. 2281-2290, MAY 22 2018.
• Web of Science Citations: 60

Abstract

BACKGROUND Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with beta-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/m(2)) 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 beta-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 Chemotherap-Induced Cardiotoxicity {[}CECCy] NCTO1724450)(C) 2018 by the American College of Cardiology Foundation. (AU)

• FAPESP's process: 10/18078-8 - Double-blind randomized and controled trial of beta-blocker effect in the prevention of Chemotherapy-induced Cardiomyopathy
• Grantee: Edimar Alcides Bocchi
• Support Opportunities: Research Projects - Thematic Grants