The SARAH trial – D’après la présentation « Effects of Sacubitril-Valsartan on Prevention of CArdiotoxicity in High-Risk Patients Undergoing Anthracycline Chemotherapy” – Marcely Gimenes Bonatto, University of São Paulo in Curitiba, Brazil.
Key message
A widely used heart failure drug, sacubitril/valsartan, was associated with a lower risk of myocardial injury compared with placebo in high-risk cancer patients treated with heart failure chemotherapies. anthracycline.
Introduction
The effects of sacubitril/valsartan (RNAi) on anthracycline-induced cardiotoxicity are unknown. Experimental studies suggest potential cardioprotection. The authors tested the hypothesis that Sacubitril-Valsartan is effective in reducing cardiotoxicity in high-risk patients receiving anthracycline (ATN)-based chemotherapy.
Method
The SARAH study is a prospective, randomized, double-blind, placebo-controlled trial. One hundred and fourteen high-risk patients defined by troponin levels exceeding the 99th percentile during NTD treatment were included. 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. Assessments included biomarker testing, echocardiographic assessments, and cardiac MRI. A sample size of 100 patients was calculated based on estimated event rates of 35% in the placebo group and 12% in the Sacubitril-Valsartan group, with a power of 80% and an error rate type I of 0.05.
- Main judgment criteria: the incidence of patients with a reduction of more than 15% in global longitudinal strain (GLS) of the left ventricle (LV) after 6 months.
- Secondary endpoints: changes in biomarkers, GLS, left ventricular ejection fraction (LVEF), ventricular diameters, extracellular matrix, interstitial fibrosis, and adverse events from baseline to 6-month follow-up .
Results
Among patients, 90% were women, 92% were 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. 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 RNAi, compared with 25% in the placebo group (hazard ratio, 0.23; 95% confidence interval [IC]0.07 to 0.75; PTable 1). The Sacubitril-Valsartan group improved GLS by 2.5%, while the placebo group experienced a decline of 7.6% (p=0.015).
After 6 months, LVEF assessed by MRI increased by 0.19% in the Sacubitril-Valsartan group and decreased by 3.47% in the control group (p=0.01). The variations in LVEF, TD volume and TS evaluated by MRI and echocardiography are presented in the Tableau 2.
Tableau 1 : incidence of patients with a reduction of more than 15% in global longitudinal strain (GLS) of the left ventricle after 6 months (Primary endpoint)
Tableau 2 : change in LVEF, LV end-diastolic and end-systolic volume during follow-up (one of the secondary endpoints)
Regarding side effects, more patients in the Sacubitril-Valsartan group suffered from low blood pressure and had an increase in serum potassium.
Conclusion
In the discussion, Dr. Bonnie Ky emphasizes that it will be necessary to confirm these results on a large population. It indicates that left ventricular dysfunction was significant in this study at 24 weeks (FEVGThe SARAH trial is the first study to show the cardioprotective potential of RNAi in high-risk patients receiving ATN treatment. Ventricular dysfunction assessed by the reduction in LV GLS was significantly lower in patients receiving Sacubitril-Valsartan than in those receiving placebo.
All the latest news from the AHA
Related News :