Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: The effects of sacubitril/valsartan (ARNi) on anthracycline-induced cardiotoxicity are unclear. Experimental studies suggest potential cardioprotection. We tested the hypothesis that ARNi is effective in reducing cardiotoxicity in high-risk patients receiving anthracycline (ATN) chemotherapy.
Study Design and Methods: Prospective randomized, double-blind, placebo-controlled trial.
Sample Size: 114 patients.
Population Studied: High-risk patients defined by troponin levels exceeding the 99th percentile during ATN treatment.
Intervention(s): Participants were randomized in a 1:1 ratio to receive either ARNi or a placebo for 6 months, with a target dose of 97/103 mg twice daily. Evaluations included biomarkers, echocardiographic assessments, and cardiac magnetic resonance (CMR).
Power Calculations: A sample size of 100 patients was calculated based on estimated event rates of 35% in the placebo group and 12% in the ARNi group, with 80% power and a type I error rate of 0.05.
Primary End Points: The incidence of patients exhibiting a greater than 15% reduction in global longitudinal stain (GLS) of the left ventricle (LV) after 6 months.
Secondary End Points: Changes in biomarkers, GLS, LV ejection fraction (EF), ventricular diameters, extracellular matrix, interstitial fibrosis and adverse events from baseline to 6 months.
Outcome(s): Among patients 90% were women, 92% white, the mean age was 51.7 ± 11,6 years, and 64% had at least one comorbidity. The ATN dose was 244 ± 40,5 mg/m². The baseline GLS and LVEF were -20.1% (-15.5% to -29%) and 64% (53.1% to 79.2%), respectively. The primary endpoint was achieved in 7.1% of patients receiving ARNi, compared to 25% in the placebo group (hazard ratio, 0.23; 95% confidence interval [CI], 0.07 to 0.75; P<0.015). The ARNi group improved GLS by 2.5%, whereas the placebo group experienced a 7.6% decline (p=0.015). After 6 months, the LVEF assessed by CMR increased by 0.19% in the ARNi group and decreased by 3.47% in the control group (p=0.011). No significant between-group differences were observed in biomarkers and other echocardiographic or CMR parameters. A higher number of patients in the ARNi group experienced hypotension. The SARAH TRIAL is the first study to demonstrate the cardioprotective potential of ARNi in high-risk patients receiving ATN therapy. Ventricular dysfunction assessed by reductions in LV GLS was significantly lower in patients receiving ARNi than in those on placebo.