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. Δ logBNP/ Δ Hb 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.