**Background:** Chronic heart failure (CHF) and renal anemia are common comorbidities that form a vicious cycle known as cardio-renal-anemia syndrome, leading to worsening of both cardiac and renal function. Erythropoiesis-stimulating agents (ESAs) have shown benefits in improving NYHA class and reducing hospitalizations, but the effects of continuous erythropoietin receptor activator (CERA), a long-acting ESA, on cardiac and renal function and oxidative stress in CHF patients with renal anemia had not been studied. This prospective single-arm study aimed to evaluate the impact of CERA on these parameters over 12 months.
**Methods:** Sixty patients with CHF (NYHA I-III) and renal anemia (hemoglobin ≤ 11 g/dL, CKD stage 3b or lower) were enrolled at Sekino Hospital, Japan. CERA was administered intravenously as an add-on treatment, starting at 50 μg/month and adjusted to maintain Hb between 11 and <13 g/dL. The primary endpoints were changes in hemoglobin (Hb) and hematocrit (Ht). Secondary endpoints included atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), NYHA class, echocardiographic parameters (LVEF, LVMI, etc.), renal function markers (BUN, sCr, eGFR, cystatin C, urinary albumin), high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (Ox-LDL), and renin-angiotensin-aldosterone system components. Measurements were taken at baseline and at 1, 3, 6, and 12 months. Statistical analysis used one-way ANOVA with p < 0.05 considered significant.
**Key Results:** No deaths, cardiac/renal events, thrombosis, or adverse reactions occurred. The mean maintenance dose of CERA at month 12 was 82.0 ± 4.8 μg/month. Hb levels increased significantly from baseline (9.8 ± 0.1 g/dL) to all time points (month 12: 12.2 ± 0.2 g/dL, all p < 0.001). Ht also increased significantly (baseline: 30.4 ± 0.4%; month 12: 37.5 ± 0.5%, all p < 0.001). BNP decreased significantly from baseline (174.2 ± 21.2 pg/mL) to month 12 (111.7 ± 12.2 pg/mL, p = 0.001). ANP decreased significantly from baseline (104.9 ± 9.1 pg/mL) to months 3, 6, and 12 (month 12: 83.9 ± 6.8 pg/mL, p < 0.001). NYHA class improved significantly at months 6 and 12 (p = 0.007). Among echocardiographic parameters, only left ventricular mass index (LVMI) decreased significantly from baseline to month 12 (p = 0.008). Renal function improved: sCr decreased significantly at months 3, 6, and 12 (p < 0.001 to p = 0.001); eGFR increased significantly at all time points (p < 0.001); cystatin C decreased significantly at months 3, 6, and 12 (p = 0.03, 0.033, 0.038). Ox-LDL decreased significantly at months 6 (p = 0.036) and 12 (p = 0.017). Angiotensin-II levels decreased significantly from baseline to month 12 (p = 0.003). No significant changes were seen in LVEF, hs-CRP, or other RAAS components.
**Clinical Implications:** This study demonstrates that CERA treatment for 12 months in patients with CHF and renal anemia not only corrects anemia but also reduces cardiac stress (as evidenced by decreased BNP, ANP, and LVMI), improves renal function (sCr, eGFR, cystatin C), and lowers oxidative stress (Ox-LDL). These findings suggest that CERA may help break the cardio-renal-anemia vicious cycle, potentially preventing further deterioration of heart and kidney function. The safety profile was favorable with no thrombotic events. However, the single-arm design and lack of a control group limit the ability to attribute improvements solely to CERA. The results provide a useful baseline for future studies comparing CERA with newer agents like HIF-PH inhibitors. Larger, randomized controlled trials with longer follow-up are needed to confirm these benefits and assess impact on hard outcomes such as mortality and hospitalizations.