Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on hemoglobin, B-type natriuretic peptide, and renal function in anemic heart failure patients: A systematic review and meta-analysis

Abstract

Background: Anemia is a common comorbidity in heart failure (HF) patients, often leading to worsened outcomes. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors represent a novel approach for anemia management, yet their efficacy and safety in HF patients remain unclear. We aimed to conduct a systematic review and meta-analysis of studies on the effects of HIF-PH inhibitors on hemoglobin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), or estimated glomerular filtration rate (eGFR) in HF patients with chronic kidney disease (CKD).

Methods and results: The search of electronic databases identified four studies including 98 patients. Among the included studies, two were conducted prospectively, while two were retrospective in design. No studies were identified that compared HIF-PH inhibitors with erythropoiesis-stimulating agents or placebo. In cases of significant heterogeneity (I² > 50 %), data were pooled using a random-effects model; otherwise, a fixed-effects model was used. In pooled analyses, hemoglobin levels increased at one (weighted mean difference [WMD]: 0.697 [0.473, 0.920] g/dL; P_fix < 0.001; I² = 24 %) and three months (WMD: 0.760 [0.443, 1.076] g/dL; P_fix < 0.001; I² = 31 %) after the use of HIF-PH inhibitors. NT-proBNP levels showed a modest decrease at one month but no significant changes at three months. eGFR remained unchanged, and no severe adverse events were reported.

Conclusion: This meta-analysis suggests that HIF-PH inhibitors effectively improve anemia in HF patients with CKD without notable changes in renal or HF-related biomarkers. However, the small number of included studies and the absence of a comparator group underscore the need for cautious interpretation of the findings.

Keywords: Anemia; Heart failure; Hypoxia-inducible factor prolyl hydroxylase inhibitors; Meta-analysis; Systematic review.

Fig. 1

Selection process for studies included in meta-analysis.

Fig. 2

Forest plots showing the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on hemoglobin (Hb) levels (g/dL) at one (a) and three (b) months.

Fig. 3

Forest plots showing the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels ln(pg/ml) at one (a) and three (b) months and on eGFR levels (mL/min/1.73 m²) at three months (c).