LONG-TERM SAFETY OF HYPOXIA INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITORS IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS
JEFFREY T. HA1,2,3, SWAPNIL HIREMATH4, MIN JUN2,3, SUETONIA C. PALMER5, DAVID C. WHEELER6, DANIEL W. COYNE7, VLADO PERKOVIC2,3, SUNIL V. BADVE 1,2,3 1Department of Renal Medicine, St George Hospital, Sydney, NSW, Australia2The George Institute for Global Health, Sydney, NSW, Australia3Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia4Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada5Department of Medicine, University of Otago, Christchurch, New Zealand6Department of Renal Medicine, University College London, London, United Kingdom7Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri, USA
Abstract
Background: Hypoxia inducible factor (HIF)-prolyl hydroxylase inhibitors are an alternative to erythropoiesis-stimulating agents (ESA) to treat anaemia of chronic kidney disease (CKD).
Aim: We assessed long-term safety of HIF-prolyl hydroxylase inhibitors in CKD.
Methods: In this systematic review and meta-analysis, MEDLINE, Embase and Cochrane databases were searched to March 2023. Randomised trials comparing HIF-prolyl hydroxylase inhibitors to ESA or placebo with ≥48 weeks of follow-up were eligible for inclusion. Primary outcome was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke (PROSPERO registration CRD42021278011).
Results: Twenty-five trials involving 26,478 participants were eligible (13 trials involving 13,230 participants with dialysis-dependent CKD, and 12 trials involving 13,248 participants with non-dialysis CKD at baseline). There was little to no difference in MACE between HIF-prolyl hydroxylase inhibitors and ESA in dialysis-dependent CKD (RR 0·99, 95% CI 0·92 to 1·08) and non-dialysis CKD (RR 1·08, 95% CI 0·95 to 1·22), and between HIF-prolyl hydroxylase inhibitors and placebo (RR 1·10, 95% CI 0·96 to 1·27) in non-dialysis CKD. Findings were consistent for individual components of MACE, and cardiovascular death across all comparisons. The non-cardiovascular safety profile of HIF-prolyl hydroxylase inhibitors was similar to ESA in dialysis-dependent CKD. In non-dialysis CKD, dialysis access thrombosis, venous thromboembolism, infections, hyperkalaemia and seizures occurred more frequently in the HIF-prolyl hydroxylase inhibitor group than the placebo group. In non-dialysis CKD, oesophageal or gastric erosion was more frequent with HIF-prolyl hydroxylase inhibitors than ESA.
Conclusions: The long-term safety profile of HIF-prolyl hydroxylase inhibitors was similar to ESA in dialysis-dependent CKD. In patients with non-dialysis CKD, HIF-prolyl hydroxylase inhibitors may be a reasonable alternative to ESA but used with caution.
Biography
Jeffrey is a nephrologist at Canterbury Hospital in the Sydney Local Health District. He is completing a PhD through The George Institute for Global Health, to better understand and manage the high burden of cardiovascular disease in patients with kidney disease. His research interests are in epidemiology, clinical trials, and expertise in anticoagulation and the treatment of cardiovascular disease in CKD. He also currently serves as an Editorial Fellow with the American Journal of Kidney Diseases.