Hypoxia-inducible factor prolyl- hydroxylase inhibitors for anaemia in patients with chronic kidney disease: Analysis of adverse events

Hypoxia-inducible factor prolyl-hydroxylase inhibitors are a newer class of orally administered drugs for the treatment of anaemia in chronic kidney disease (CKD). Several meta-analyses have shown HIF-PHIs to have comparable efficacy to erythropoiesis stimulating agents (ESAs), however, evaluation of the safety of HIF-PHIs is ongoing.

This systematic review and meta-analysis evaluated the cardiac and kidney-related adverse effects of HIF-PHIs among patients with CKD and anaemia, compared with placebo or an erythropoiesis stimulating agent (ESA).

The meta-analysis of 23 trials found no differences in the risk of cardiac events, kidney-related adverse events, progression to end-stage kidney disease or starting dialysis, drug-related serious adverse events, or death detected between the HIF-PHIs group and the placebo or ESAs groups.

HIF-PHIs were associated with a significant increase in the risk of hypertension when compared to placebo, but with less risk of hypertension when compared with parenteral ESA. Other secondary findings include a higher risk of hyperkalaemia in the HIF-PHIs group compared to the placebo group, but comparable risk to that in the ESA group. Importantly, these risks do not seem to translate into clinical outcomes, including cardiac- or kidney-related adverse events.

These agents are now available in the UK for initiation in patients with non-dialysis CKD with iron replete anaemia at a comparable price to ESA therapy and will be an attractive alternative for many clinicians, patients and clinical services.

The full study can be read here.