Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis
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 (...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1163908/full |
| _version_ | 1797821479042154496 |
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| author | Dinghua Chen Yue Niu Fei Liu Yue Yang Xue Wang Ping Li Xiangmei Chen |
| author_facet | Dinghua Chen Yue Niu Fei Liu Yue Yang Xue Wang Ping Li Xiangmei Chen |
| author_sort | Dinghua Chen |
| collection | DOAJ |
| description | 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.Systematic review registration: This study is registered with PROSPERO (registration number CRD42022312252) |
| first_indexed | 2024-03-13T09:53:18Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T09:53:18Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-2377cc7668af4d689942245aca9b3e5c2023-05-24T04:28:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11639081163908Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysisDinghua Chen0Yue Niu1Fei Liu2Yue Yang3Xue Wang4Ping Li5Xiangmei Chen6Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Urology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, ChinaAim: 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.Systematic review registration: This study is registered with PROSPERO (registration number CRD42022312252)https://www.frontiersin.org/articles/10.3389/fphar.2023.1163908/fullhypoxia-inducible factor prolyl hydroxylase inhibitorschronic kidney diseaseanemiarenal dialysisadverse eventerythropoiesis-stimulating agent |
| spellingShingle | Dinghua Chen Yue Niu Fei Liu Yue Yang Xue Wang Ping Li Xiangmei Chen Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis Frontiers in Pharmacology hypoxia-inducible factor prolyl hydroxylase inhibitors chronic kidney disease anemia renal dialysis adverse event erythropoiesis-stimulating agent |
| title | Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis |
| title_full | Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis |
| title_fullStr | Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis |
| title_full_unstemmed | Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis |
| title_short | Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis |
| title_sort | safety of hif prolyl hydroxylase inhibitors for anemia in dialysis patients a systematic review and network meta analysis |
| topic | hypoxia-inducible factor prolyl hydroxylase inhibitors chronic kidney disease anemia renal dialysis adverse event erythropoiesis-stimulating agent |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1163908/full |
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