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Introduction: This integrated phase 3 analysis examined efficacy and cardiovascular safety for roxadustat vs erythropoiesis-stimulating agents (ESAs) in dialysis-dependent patients. Methods: Efficacy and safety results from four phase 3, randomized, open-label studies comparing roxadustat to ESAs (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES) in dialysis-dependent patients with anemia of chronic kidney disease (CKD) were evaluated by study, pooled population and in two subgroups: incident dialysis and stable dialysis. The primary efficacy endpoint per study was hemoglobin change from baseline (CFB) to weeks 28–36 using least-squares mean difference (LSMD) without rescue therapy. Pooled safety endpoints included time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality [ACM]) and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for non-inferiority at 1.8 and 1.3 margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized. Results: In total, 4714 patients were randomized (2354 roxadustat; 2360 ESA). Hemoglobin CFB to weeks 28–36 achieved non-inferiority for roxadustat vs ESA in each study. Roxadustat was non-inferior to ESA for risks for MACE and MACE+ in the entire cohort (MACE: HR 1.09, 95% CI 0.95–1.26; MACE+ : HR 0.98, 95% CI 0.86–1.11) and similar to the incident dialysis and stable dialysis subgroups; ACM results were consistent with MACE and MACE+ (HR 1.13, 95% CI 0.95–1.34). TEAEs were generally comparable between groups. Conclusion: Roxadustat improved hemoglobin similarly to ESA while demonstrating comparable cardiovascular and overall safety profiles in a wide spectrum of dialysis-dependent patients with anemia of CKD. Roxadustat represents an oral alternative to ESAs for achieving a target hemoglobin for anemia of CKD in dialysis-dependent patients. [ABSTRACT FROM AUTHOR]

Background: Anemia is a common comorbidity in patients with chronic kidney disease (CKD). That affects the vast majority and can have a significant impact on patient morbidity and mortality. Erythropoiesis-stimulating agents (ESAs) are the main lines in management of anemia in hemodialysis patients. Replacement therapy with recombinant human erythropoietin (r- HuEPO) has provided an effective treatment for patients with renal "Epoetin alfa" is a recombinant erythropoietin with the same amino acid sequence as human erythropoietin (EPO). In comparison to epoetin alfa, darbepoetin alfa (DPO) contains an increased amount of sialic acid-containing carbohydrate chains. It shows a much longer elimination half-life than epoetin alfa, with prolonged erythropoietic effect. Aim of the Work: to evaluate whether darbpoetin and epopoetin alpha can be used interchangeably on the same patient, achieving the same desired effect and to detect any difference in the occurrence of side effects between both ESAs. Patient and Methods: This was a crossover study that took place in the Pediatrics Dialysis unit, Children's Hospital, Ain Shams University. The study was conducted on 40 children with end stage renal disease on regular hemodialysis over a period of 6 months. The patients were randomly put into two groups A and B, each group contained 20 patients. Each group received one type of ESA either (darbpoetin alpha or epopoetin alpha)for 3 months and then shifted to the other type of ESA for another 3 months. The dosage of epoetin alfa used was (200IU/kg/week) and a conversion rate of EPO: DPO, 300:1. A period of 6 weeks was agreed as a washout period after the first drug given in both groups in which no results were recorded but ESA was not stopped due to its essentiality. Blood tests (hemoglobin (Hb), serum urea, serum creatinine and iron profile; (S. iron, S. ferritin, TIBC, and transferrin saturation)) were withdrawn at the start and the end of the 3 months' period of each drug. Results: We found no difference on the Hb level with both drugs. The interchange between them did not yield any significant drop in the Hb levels. Hb target in both EPO and DPO was reached in 22.5% of total cases, and was not reached in 62.5%. This proved that both drugs give the same effect with nearly negligible difference. No serious Sside effect as convulsions, hypertension, and thrombosis were noticed in both groups. Conclusion: The target Hb was not reached in most patients of both groups of ESRD on regular hemodialysis at the unit and none of both drugs showed superior results or less side effects than the other. [ABSTRACT FROM AUTHOR]