Meta-Analysis: Long-term Safety of HIF-PHIs in Patients With CKD

Anemia associated with chronic kidney disease (CKD) can be treated with oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). Jeffery Ha and colleagues recently conducted a systematic review and meta-analysis designed to assess the long-term safety of HIF-PHIs in patients with CKD.

Results were reported during a poster session at the American Society of Nephrology Kidney Week 2023. The poster was titled Long-term Safety of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in CKD: A Systematic Review and Meta-Analysis of Randomized Trials.

The researchers searched MEDLINE, Embase, and Cochrane databases to March 2023. Randomized trials comparing HIF-PHIs with an erythropoiesis-stimulating agent (ESA) or placebo with at least 48 weeks of follow-up were eligible for the review. Outcomes of interest were major adverse cardiovascular events (MACE), individual components of composite cardiovascular end points, thrombotic events, and non-cardiovascular adverse events. Separate analyses were conducted in those with CKD treated with dialysis and those not treated with dialysis.

A total of 25 trials representing 26,478 participants were eligible. Of those, 13 were conducted among 13,230 participants with dialysis-dependent CKD (DD-CKD), and 12 were conducted among 13,248 participants with non-dialysis-dependent CKD (NDD-CKD). There was no evidence indicating that HIF-PHIs and ESA had different effects on MACE in those with DD-CKD (relative risk [RR], 0.99; 95% CI, 0.92-1.08) and in those with NDD-CKD (RR, 1.08; 95% CI, 0.95-1.22).

Likewise, there was no evidence that HIF-PHIs and placebos had different effects on MACE in participants with NDD-CKD (RR, 1.10; 95% CI, 0.96-1.27). The lack of difference between HIF-PHIs and ESA or placebo was also seen for the individual components of MACE and for cardiovascular death.

In the DD-CKD group, the safety of HIF-PHIs for other outcomes was similar. In the NDD-CKD group, adverse events (dialysis access thrombosis, infection, hyperkalemia, and seizures) occurred more frequently in the HIF-PHI group compared with the placebo group. Esophageal or gastric erosion were more frequent with HIF-PHIs than with ESAs in the NDD-CKD group.

“The long-term effects of HIF-PHIs were similar to ESA in dialysis-dependent CKD,” the researchers said. “However, HIF-PHIs increased the incidence of some adverse events in non-dialysis CKD.”

Source: Ha J, Hiremath S, Jun M, et al. Long-term safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in CKD: a systematic review and meta-analysis of randomized trials. TH-PO987. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2023; November 2, 2023; Philadelphia, Pennsylvania.