Effects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors on Relationship Between B-Type Natriuretic Peptide and Hemoglobin Levels in Patients With Cardiorenal Anemia Syndrome.

BACKGROUNDS: Anemia is associated with poor prognosis in heart failure patients. Erythropoiesis-stimulating agents have been used for the treatment of renal anemia, but they increase the risk of thrombotic events. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a new treatment for renal anemia. HIF-PHIs are expected to have pleiotropic effects beyond correcting anemia. Evidence regarding the effects of HIF-PHIs in cardiorenal anemia syndrome has not been established.

METHODS AND

RESULTS

The present study is a single-center, retrospective analysis of patients with heart failure and renal anemia who were treated with HIF-PHIs or oral iron supplementation at Kyushu University Hospital (n = 39 and n = 26). Both treatments significantly raised hemoglobin levels (HIF-PHIs 9.1 [8.6-9.6] vs. 10.3 [9.5-11.8], p < 0.001; oral iron 10.1 [9.3-11.0] vs. 11.8 [10.6-13.2], p < 0.001). Log-transformed BNP level (logBNP) decreased in the HIF-PHI-treated patients but not in those treated with oral iron despite the similar improvement in hemoglobin levels (HIF-PHIs 2.74 [2.28-2.99] vs. 2.47 [2.16-2.66], p = 0.005; oral iron 2.38 [1.89-2.66] vs. 2.37 [1.90-2.50], p = 0.711). The levels of iron metabolism-related parameters after treatment were comparable between the two groups. ΔlogBNP/ΔHb slope was significantly steeper in the HIF-PHI group than the oral iron supplementation group (-0.100 vs. -0.047, p = 0.039), meaning that HIF-PHIs further reduced BNP levels than anticipated by the increase of hemoglobin with conventional treatment.

CONCLUSION

HIF-PHIs reduce BNP levels more than anticipated by the elevation of hemoglobin levels compared to oral iron supplementation. HIF-PHIs may have therapeutic benefits against heart failure beyond the correction of anemia in the heart failure patients.