Mohamed M G Mohamed1, Mosunmoluwa Oyenuga2, Safia Shaikh2, Abayomi Oyenuga3, Babikir Kheiri4, Christian Nwankwo5. 1. Department of Internal Medicine, SSM Health St. Mary's Hospital-St.Louis, 6420 Clayton Rd, Suite 2218, St. Louis, MO, 63117, USA. Mohamed.mohamed@ssmhealth.com. 2. Department of Internal Medicine, SSM Health St. Mary's Hospital-St.Louis, 6420 Clayton Rd, Suite 2218, St. Louis, MO, 63117, USA. 3. Department of Internal Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. 4. Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA. 5. Department of Nephrology, SSM Health St. Mary's Hospital-St. Louis, St. Louis, MO, USA.
Abstract
PURPOSE: Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies. METHODS: We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software. RESULTS: We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea. CONCLUSION: HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.
PURPOSE: Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies. METHODS: We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software. RESULTS: We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea. CONCLUSION: HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.
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Authors: Ajay K Singh; Kevin Carroll; John J V McMurray; Scott Solomon; Vivekanand Jha; Kirsten L Johansen; Renato D Lopes; Iain C Macdougall; Gregorio T Obrador; Sushrut S Waikar; Christoph Wanner; David C Wheeler; Andrzej Więcek; Allison Blackorby; Borut Cizman; Alexander R Cobitz; Rich Davies; Tara L DiMino; Lata Kler; Amy M Meadowcroft; Lin Taft; Vlado Perkovic Journal: N Engl J Med Date: 2021-11-05 Impact factor: 91.245
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