Methoxy polyethylene glycol epoetin beta and the treatment of anaemia in chronic heart failure

Abstract

Aim. To study erythropoietic activity and safety of methoxy polyethylene glycol epoetin beta (MEB) and its effects on haemoglobin (Hb), erythropoietin, ferritin, NT-proBNP, cytokines, and chronic heart failure (CHF) symptoms and signs. Material and methods. In total, 84 patients with Functional Class (FC) II–IV (NYHA) CHF and anaemia were examined (mean age 59,7±1,6 years; 54 men and 30 women). Anaemia criteria were Hb levels <120 g/l in men and <110 g/l in women. CHF was due to coronary heart disease, CHD (post-infarction cardiosclerosis; n=40); to CHD in combination with Type 2 diabetes mellitus, DM-2 (n=10), and arterial hypertension, AH (n=14); and to the combination of CHD, AH, and DM-2 (n=10). Left ventricular ejection fraction (LVEF) in CHF patients with FC II, III, and IV was ≤45%, ≤40%, and ≤30%, respectively. At baseline and after 6 months of MEB treatment, the levels of ferritin, transferrin, erythropoietin, NT-proBNP, and pathologic cytokines were assessed. MEB was administered to patients without iron deficiency. All participants were randomised into two groups: Group I (n=44) received standard treatment with ACE inhibitors, digoxin, beta-blockers, and diuretics; Group II (n=40) received standard therapy and subcutaneous MEB (0,60 mkg/kg (50 U) once a month, for 6 months). Results. LVEF in Group II increased by 23,3% (р<0,02). Exercise capacity (6-minute walk test), decreased at baseline, also significantly increased in patients receiving MEB, compared to individuals receiving placebo (+42,8%; p<0,01). Positive hemodynamic effects were accompanied by a marked clinical improvement, as demonstrated by a reduced need for diuretics (–32–35%) and by the quality of life improvement. In Group I, mean Hb levels significantly increased and reached 104,5 g/l, while in Group II, this significant increase was even higher (up to 113,7 g/l). Group II, compared to Group I, demonstrated an increase in Hb levels by 21,9% (p<0,05) and normalisation of erythropoietin levels. Of note, an increase in erythropoietin levels was accompanied by a slight reduction in ferritin levels (up to 102,7±21,2 mkg/l) in participants with ferritin saturation >20%. In Group II, the increase in erythropoietin levels was associated with suppressed cytokine activation, decreased levels of interleukin-6 (–48,4%; p<0,05) and tumour necrosis factor-alpha (–39,7%; p<0,01), and a slight increase in interleukin-1 levels (+0,97%; p<0,02). Conclusion. The use of MEB for the anaemic syndrome correction in CHF patients effectively treats erythropoietin deficiency, anaemia, and cytokine activation.