Differences in efficacy and safety between HIF-PHIS and ESA/placebo in a sample of hemodialysis patients: a systematic review and meta-analysis

Treatment of anemia is one of the main goals of supportive care in patients on hemodialysis. In this context, the use of therapy with hypoxia inducible factor inhibitors (HIF-PHI) represents a further promising resource. The main objective is to evaluate the difference in hemoglobin levels after treatment with HIF-PHI compared to placebo/ESA. We performed a systematic search in PubMed, CINAHL, EMBASE, and Register of Controlled Trials (CENTRAL), looking for randomized controlled trials (RCTs). Eligible studies considered hemodialysis patients older than 18 years with the diagnosis of anemia treated with HIF-PHIs. Protocol was previously published on PROSPERO (CRD42024589848). Among a total of 126 references, 32 citations were selected by screening of titles and abstracts, for full-text evaluation, and 14 articles referring were included in the review after the screening for full-text articles. Data on hemoglobin differences were reported by all studies and the pooled analysis involving 3890 patients (2267 in the experimental group and 1623 in the control group), network metanalysis did not show significant differences in Delta Hemoglobin among any HIF-PHIs types and ESA/placebo. Similarly, no significant differences were found comparing HIF-PHIs to ESA Splitting (11 studies, N.=3611). However, a significant difference was found comparing HIF-PHIs to Placebo (MD=1.48, 95%CI: 1.15/1.81, P<0.001). The experimental and control groups differed for gastrointestinal adverse events, whereas there were no differences for any other adverse events. The similar efficiency and safety between HIF-PHIs and ESA care could modify the usual clinical treatment of anemia in hemodialysis patients, and allow personalized therapy.