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Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors.
MEDLINE, Embase and Cochrane databases were searched for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with ≥48 weeks of follow-up. The primary review outcome was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction or stroke. Treatment effects were pooled using random-effects models.
Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio [RR] 0.99, 95% CI 0.92 to 1.08) and nondialysis-dependent CKD (RR 1.08, 95% CI 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (RR 1.10, 95% CI 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable to ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials; whereas seizures occurred more frequently with HIF prolyl hydroxylase inhibitors, irrespective of the comparator. Compared with ESA, esophageal or gastric erosion occured more frequently with HIF prolyl hydroxylase inhibitors in nondialysis-dependent CKD, but less frequently in dialysis-dependent CKD.
There was no difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and nondialysis-dependent CKD. This abstract was also submitted for the ASN Kidney Week 2023 congress. By submitting the abstract to WCN’24, abstract authors declare that re-submitting the abstract is permitted by the organizers of the previous meeting.