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

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. 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. 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]; <i>P=</i>0.015). The sacubitril-valsartan group showed a 2.5% improvement in global longitudinal strain, whereas the placebo group experienced a 7.6% decline (<i>P</i><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; <i>P</i>=0.032). 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. URL: https://ensaiosclinicos.gov.br/rg/RBR-5q4gm5b; UTN code: U1111-1274-1961.