COMPARATIVE EFFECTIVENESS AND SAFETY OF HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITORS COMPARED WITH ERYTHROPOIESIS-STIMULATING AGENTS FOR ANEMIA ASSOCIATED WITH CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Author(s)
GAUTAM SAHU, MS, PhD, Sandeep Arora, MS, PhD, Tapan Behl, MS, PhD.
Pharmacy, Amity Institute of Pharmacy, Amity University Punjab, Mohali, Punjab, India, SAS NAGAR, PUNJAB, India.
Pharmacy, Amity Institute of Pharmacy, Amity University Punjab, Mohali, Punjab, India, SAS NAGAR, PUNJAB, India.
OBJECTIVES: Anemia is a frequent complication of chronic kidney disease (CKD). Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as oral alternatives to erythropoiesis-stimulating agents (ESAs). This study compared their effectiveness and safety to inform evidence-based treatment decisions.
METHODS: PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus were systematically searched from inception to March 2026. Randomized controlled trials of HIF-PHIs compared with ESAs in adult patients with anemia and CKD. The main outcomes were a change in haemoglobin concentration and target levels of haemoglobin. Secondary outcomes were transferrin saturation (TSAT), ferritin, major adverse cardiovascular events (MACE), thromboembolic events, serious adverse events (SAEs), all-cause mortality and treatment discontinuation. We performed random-effects meta-analysis using Review Manager 5.4. The risk of bias was assessed with the Cochrane RoB 2 tool.
RESULTS: Twenty-one randomized controlled trials with 15,842 patients fulfilled the inclusion criteria. HIF-PHIs were associated with significantly higher hemoglobin compared to ESAs (MD=0.31 g/dL; 95% CI: 0.18-0.44; p<0.001) and increased likelihood of achieving target hemoglobin levels (RR=1.12; 95% CI: 1.05-1.20). HIF-PHIs also reduced intravenous iron use (MD=−18.7 mg/month; 95% CI: −29.8 to −7.6) and increased indices of iron utilisation. There were no significant differences for MACE (RR=1.03; 95% CI: 0.94-1.13), all-cause mortality (RR=0.98; 95% CI: 0.88-1.10), SAEs (RR=1.01; 95% CI: 0.95-1.08) or thromboembolic events (RR=1.05; 95% CI: 0.89-1.23). The evidence was moderate to highly certain.
CONCLUSIONS: HIF-PHIs are effective in improving hemoglobin levels and iron utilization and seem to be safe compared to ESAs in treating anemia associated with CKD. The findings support the use of these products in evidence based anemia management and provide relevant evidence for health technology assessment, reimbursement decisions and value-based healthcare.
METHODS: PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus were systematically searched from inception to March 2026. Randomized controlled trials of HIF-PHIs compared with ESAs in adult patients with anemia and CKD. The main outcomes were a change in haemoglobin concentration and target levels of haemoglobin. Secondary outcomes were transferrin saturation (TSAT), ferritin, major adverse cardiovascular events (MACE), thromboembolic events, serious adverse events (SAEs), all-cause mortality and treatment discontinuation. We performed random-effects meta-analysis using Review Manager 5.4. The risk of bias was assessed with the Cochrane RoB 2 tool.
RESULTS: Twenty-one randomized controlled trials with 15,842 patients fulfilled the inclusion criteria. HIF-PHIs were associated with significantly higher hemoglobin compared to ESAs (MD=0.31 g/dL; 95% CI: 0.18-0.44; p<0.001) and increased likelihood of achieving target hemoglobin levels (RR=1.12; 95% CI: 1.05-1.20). HIF-PHIs also reduced intravenous iron use (MD=−18.7 mg/month; 95% CI: −29.8 to −7.6) and increased indices of iron utilisation. There were no significant differences for MACE (RR=1.03; 95% CI: 0.94-1.13), all-cause mortality (RR=0.98; 95% CI: 0.88-1.10), SAEs (RR=1.01; 95% CI: 0.95-1.08) or thromboembolic events (RR=1.05; 95% CI: 0.89-1.23). The evidence was moderate to highly certain.
CONCLUSIONS: HIF-PHIs are effective in improving hemoglobin levels and iron utilization and seem to be safe compared to ESAs in treating anemia associated with CKD. The findings support the use of these products in evidence based anemia management and provide relevant evidence for health technology assessment, reimbursement decisions and value-based healthcare.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO181
Topic
Clinical Outcomes, Epidemiology & Public Health, Health Technology Assessment
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Personalized & Precision Medicine, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain), Urinary/Kidney Disorders