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
Marcely Gimenes Bonatto, Mônica Samuel Ávila, Silvia Moreira Ayub‐Ferreira, Luka David Lechinewski, Rafael Torres, Amanda de Nadai Costa, Nadya Rocumback Alves da Costa, Andressa de Oliveira Coiradas, Talita Beithum Ribeiro Mialski, Julyana Maiolino, Tammy Tiemy Ota, Laís Contin, Larissa Arlete Mosko, Márcio Sommer Bittencourt, Sanderson Cauduro, Lídia Zytynski Moura, Edimar Alcides Bocchi, Amanda de Nadai Costa, Andressa de Oliveira Coiradas, Edimar Alcides Bocchi, Julyana Maiolino, Laís Contin, Larissa Arlete Mosko, Lídia Ana Zytynski Moura, Luka David Leichinewski, Marcely Gimenes Bonatto, Marcio Sommer Bittencourt, Mônica Samuel Avila, Nadya Rocumback Alves da Costa, Rafael de Almeida Torres, Sanderson Cauduro, Sílvia Moreira Ayub Ferreira, Talita Beithum Ribeiro Mialski, Tammy Tiemy Ota
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.