Abstract: Objective This study aims to investigate the relationship between the angiotensin receptor enkepriliase inhibitor Sacubitril/Valsartan and the occurrence of anemia in patients with chronic heart failure (CHF) through a prospective trial, and Explore the possible influencing factors. Methods A total of 406 CHF patients who met the inclusion and exclusion criteria from Linyi People's Hospital and Linyi Hospital of Traditional Chinese Medicine from January 2021 to June 2023 were selected as the research subjects. According to the random number table method the research subjects were randomly divided into the ARNI group and the ARB group at a 1:1 ratio. At the beginning of enrollment, both groups received conventional treatment. On this basis, 203 cases in the ARB group were treated with valsartan, and 203 cases in the ARNI group were treated with sacubitril/valsartan. Before treatment and 12 months after treatment, the levels of hemoglobin content, serum ferritin, serum iron and other anemia and iron metabolism-related indicators, as well as erythropoietin (EPO), vitamin B₁₂, folic acid levels and inflammatory indicators (IL-6) were detected in both groups. The differences in the incidence and degree of anemia in the two groups 12 months after treatment were analyzed. Binary logistic regression was used to analyze the related influencing factors of anemia occurrence, and further comparative analysis was conducted on the meaningful factors. Results After 12 months of treatment, the levels of EPO, ferritin, and IL-6 in the anemic patients in both groups were all increased compared with those before treatment. In the non-anemic patients in the ARNI group, the ferritin level showed a decreasing trend after treatment, while in the ARB group, it showed an increasing trend. The inflammatory indicator IL-6 in the non-anemic groups of both groups showed a decreasing trend. All the above differences were statistically significant (P<0.05). The incidence of anemia in the ARNI group was lower than that in the ARB group, and the degree of anemia in the ARNI group was milder than that in the ARB group, with statistically significant differences (P<0.05). Binary logistic regression analysis indicated that higher EPO levels, increased ferritin levels, and a high inflammatory state were common predictive factors for the occurrence of anemia in patients in both groups. While advanced age (≥65 years old) and poorer cardiac function classification were only risk factors for the occurrence of anemia in the ARB group. The increase level of EPO before and after treatment in anemic patients in the ARNI group was significantly higher than that in the ARB group, while the increase levels of ferritin and inflammatory indicators before and after treatment in anemic patients in the ARB group were significantly higher than those in the ARNI group, with statistically significant differences (P<0.05). Conclusion Both sacubitril/valsartan and valsartan have the risk of causing anemia in patients with chronic heart failure, but the incidence and degree of anemia caused by sacubitril/valsartan are lower. Higher EPO level, increased ferritin level, and high inflammatory state are common predictive factors for anemia in patients with chronic heart failure caused by the two drugs, but advanced age and poorer cardiac function classification are only risk factors for anemia caused by taking valsartan orally. This difference may be attributed to the fact that sacubitril/valsartan can affect the secretion of EPO, the absorption and utilization of iron, and the inhibition of inflammation in patients with heart failure.

Key words: sacubitril/valsartan, chronic heart failure, anemia, factor analysis