Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis

by Selleckchem | Sep 18 2023

Aim: We performed a systematic review and network meta-analysis evaluating the safety and efficacy of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among dialysis chronic kidney disease patients.

Methods: Safety was evaluated with any adverse events (AEs), serious adverse events (SAEs), and 12 common events. Efficacy was mainly analyzed with hemoglobin response. All reported results were summarized using mean difference and risk ratio (RR) with 95% confidence interval (CI). Publication bias was assessed through funnel plots.

Results: Twenty trials (19 studies) with 14,947 participants were included, comparing six HIF-PHIs with erythropoiesis-stimulating agents (ESAs). No significant differences were indicated in overall AEs and SAEs between each HIF-PHI and ESA. The occurrence of gastrointestinal disorder was higher in enarodustat and roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52-31.40, p = 0.01; RR: 1.30, 95% CI: 1.04-1.61, p = 0.02). The occurrence of hypertension was lower in vadadustat than in ESAs (RR: 0.81, 95% CI: 0.69-0.96, p = 0.01). The occurrence of vascular-access complications was higher in roxadustat (RR: 1.15, 95% CI: 1.04-1.27, p<0.01) and lower in daprodustat (RR: 0.78, 95% CI: 0.66-0.92, p<0.01) than in ESAs. In the risk of the other nine events, including cardiovascular events, no significant differences were observed between HIF-PHIs and ESAs. For hemoglobin response, network meta-analysis showed that compared with ESAs, significant increases were shown in roxadustat (RR: 1.04, 95% CI: 1.01-1.07, p<0.01) and desidustat (RR: 1.22, 95% CI: 1.01-1.48, p = 0.04), whereas noticeable reductions were indicated in vadadustat (RR: 0.88, 95% CI: 0.82-0.94, p<0.01) and molidustat (RR: 0.83, 95% CI: 0.70-0.98, p = 0.02). There was no significant difference between daprodustat and ESAs (RR: 0.97, 95% CI: 0.89-1.06, p = 0.47).

Conclusion: Although HIF-PHIs did not show significant differences from ESAs in terms of overall AEs and SAEs, statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications were observed between HIF-PHIs, which deserved to be noted in clinical decision making.

Comments:

Summary of the study: The aim of this systematic review and network meta-analysis was to evaluate the safety and efficacy of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among chronic kidney disease patients on dialysis. The study included 20 trials involving 14,947 participants and compared six HIF-PHIs with erythropoiesis-stimulating agents (ESAs).

Safety was assessed based on adverse events (AEs), serious adverse events (SAEs), and 12 common events. No significant differences were found in overall AEs and SAEs between each HIF-PHI and ESA. However, the occurrence of gastrointestinal disorder was higher in enarodustat and roxadustat compared to ESAs. Hypertension was less common with vadadustat than with ESAs. Vascular-access complications were more frequent with roxadustat and less common with daprodustat compared to ESAs. No significant differences were observed in the risk of other events, including cardiovascular events, between HIF-PHIs and ESAs.

Efficacy was primarily assessed using hemoglobin response. The network meta-analysis revealed that compared to ESAs, roxadustat and desidustat showed significant increases in hemoglobin response, while vadadustat and molidustat showed noticeable reductions. Daprodustat did not significantly differ from ESAs in terms of hemoglobin response.

In conclusion, HIF-PHIs did not significantly differ from ESAs in terms of overall AEs and SAEs. However, there were statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications among HIF-PHIs, which should be considered in clinical decision-making.

Note: The information provided is a summary of the findings presented in the study and should not be considered as medical advice.