{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:48:43Z","timestamp":1792396123667,"version":"4.4.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Anemia is common in heart failure (HF) patients with chronic kidney disease (CKD) and is associated with worse outcomes. Iron supplementation improves symptoms and is associated with reduced risk of hospitalization for HF in iron-deficiency HF patients. However, iron deficiency is present in &lt;30% of anemic HF patients. Erythropoiesis stimulating agents (ESAs) improve symptoms but are associated with increased risk of thromboembolic events in anemic HF patients with CKD. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia. These agents work by stabilizing the HIF complex, thereby stimulating endogenous erythropoietin production. We hypothesized that HIF-PH inhibitors may be associated with reduced risk of cardiovascular outcomes compared with ESAs in anemic HF patients with CKD. Accordingly, we aim to perform the meta-analysis of studies on the efficacy and safety of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This meta-analysis will include prospective cohort studies and randomized controlled trials on the effect of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be cardiovascular death. The secondary outcomes will be all-cause death, hospitalization for HF, HF symptoms, exercise capacity, health-related quality of life, and hemoglobin levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>This meta-analysis will evaluate the effect of HIF-PH inhibitors in anemic HF patients with CKD, providing evidence regarding the use of HIF-PH inhibitors in these patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Systematic review registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/inplasy.com\/INPLASY202230103\" xlink:type=\"simple\">INPLASY202230103<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0275311","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T18:24:28Z","timestamp":1664389468000},"page":"e0275311","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypoxia-inducible factor prolyl hydroxylase inhibitors for anemia in heart failure patients: A protocol for systematic review and 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An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals","volume":"2","author":"K Thorlund","year":"2010","journal-title":"Clin Epidemiol"},{"key":"pone.0275311.ref022","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/nep.13835","article-title":"Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors","volume":"26","author":"DYH Yap","year":"2021","journal-title":"Nephrology (Carlton)"},{"key":"pone.0275311.ref023","doi-asserted-by":"crossref","first-page":"e011130","DOI":"10.1161\/JAHA.118.011130","article-title":"Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease","volume":"8","author":"MF Eisenga","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"pone.0275311.ref024","doi-asserted-by":"crossref","first-page":"e14434","DOI":"10.14814\/phy2.14434","article-title":"Erythropoietin and a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) lowers FGF23 in a model of chronic kidney disease (CKD)","volume":"8","author":"ML Noonan","year":"2020","journal-title":"Physiol Rep"},{"key":"pone.0275311.ref025","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1253\/circj.CJ-19-1039","article-title":"Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice","volume":"84","author":"H Deguchi","year":"2020","journal-title":"Circ J"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0275311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T18:24:56Z","timestamp":1664389496000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0275311"}},"subtitle":[],"editor":[{"given":"Frank T.","family":"Spradley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,28]]},"references-count":25,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0275311","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,28]]}}}