Sacubitril-Valsartan for the Prevention of Anthracycline Cardiotoxicity in Patients With Elevated Cardiac Troponin I Concentration During Chemotherapy: A Double-Blind Randomized Placebo-Controlled Clinical Trial: The SARAH Trial
Abstract
BACKGROUND: The clinical effects of sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, on anthracycline-induced cardiotoxicity remain unknown. Experimental evidence suggests cardioprotective properties. This study evaluated the efficacy of sacubitril-valsartan in reducing cardiotoxicity in patients with increased cardiac troponin I concentrations during anthracycline chemotherapy. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 114 patients with elevated cardiac troponin I levels during anthracycline treatment. Participants were randomized 1:1 to receive either sacubitril-valsartan or placebo for 6 months, with a target dose of 97/103 mg twice daily. The primary end point was the occurrence of a >15% reduction in the global longitudinal strain from baseline to 6 months. Secondary end points included changes in biomarkers, echocardiographic and cardiac magnetic resonance parameters, and adverse events. This trial was initially conceptualized as a pilot investigation because of its exploratory nature. Data were analyzed according to the intention-to-treat principle. RESULTS: Among the randomized patients, 90% were women, and 80.7% had breast cancer. The primary end point occurred in 4 patients (7%) in the sacubitril-valsartan group and 14 patients (25%) in the placebo group (odds ratio, 0.23 [95% CI, 0.07–0.75]; P= 0.015). The sacubitril-valsartan group showed a 2.5% improvement in global longitudinal strain, whereas the placebo group experienced a 7.6% decline ( P <0.001). No significant differences in changes in cardiac troponin I or NT-proBNP (N-terminal pro-B-type natriuretic peptide) were observed. Hypotension (systolic blood pressure <100 mm Hg) occurred more frequently in the sacubitril-valsartan group than in the placebo group (8 cases versus 1 case; P =0.032). CONCLUSIONS: The SARAH trial (Sacubitril-Valsartan for the Prevention of Anthracycline Cardiotoxicity in Patients With Elevated hs-cTnI Concentrations During Chemotherapy) demonstrated the potential of sacubitril-valsartan therapy to reduce the incidence of left ventricular dysfunction, as assessed by global longitudinal strain, in patients with elevated high-sensitivity cardiac troponin I after anthracycline treatment. REGISTRATION: URL: https://ensaiosclinicos.gov.br/rg/RBR-5q4gm5b ; UTN code: U1111-1274-1961.
Article Details
Authors (18)
Luka David Lechinewski
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Amanda de Nadai Costa
Department of Cardiovascular Imaging, Institute of Neurology of Curitiba Hospital, Paraná, Brazil (R.d.A.T., A.d.N.C.).
Andressa de Oliveira Coiradas
Department of Cardiology, Division of Heart Failure, Santa Casa of Curitiba Hospital, Paraná, Brazil (M.G.B., A.d.O.C.).
Edimar Alcides Bocchi
Heart Failure Clinics, Instituto do Coração (Incor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil (M.G.B., M.S.A., S.M.A.F., E.A.B.).
Julyana Maiolino
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Laís Contin
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Larissa Arlete Mosko
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Lídia Ana Zytynski Moura
Department of Medicine, Division of Cardiology, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil (L.A.Z.M.).
Luka David Leichinewski
Marcely Gimenes Bonatto
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Márcio Sommer Bittencourt
Center for Clinical and Epidemiologic Research, Hospital Universitario, University of Sao Paulo, Sao Paulo, Brazil (P.A.L., I.M.B., M.S.B.)
Mônica Samuel Avila
Heart Failure Clinics, Instituto do Coração (Incor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil (M.G.B., M.S.A., S.M.A.F., E.A.B.).
Nadya Rocumback Alves da Costa
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Rafael de Almeida Torres
Department of Cardiovascular Imaging, Institute of Neurology of Curitiba Hospital, Paraná, Brazil (R.d.A.T., A.d.N.C.).
Sanderson Cauduro
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Sílvia Moreira Ayub Ferreira
Heart Failure Clinics, Instituto do Coração (Incor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil (M.G.B., M.S.A., S.M.A.F., E.A.B.).
Talita Beithum Ribeiro Mialski
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).
Tammy Tiemy Ota
Department of Cardiology, Division of Cardio-Oncology, Erasto Gaertner Hospital, Curitiba, Paraná, Brazil (M.G.B., L.D.L., N.R.A.d.C., T.B.R.M., J.M., T.T.O., L.C., L.A.M., S.C.).