A pilot study of chronic, low-dose epoetin-{beta} following percutaneous coronary intervention suggests safety, feasibility, and efficacy in patients with symptomatic ischaemic heart failure
Martin W Bergmann, Sven Haufe, Florian von Knobelsdorff-Brenkenhoff, Heidrun Mehling, Ralf Wassmuth, Ines Münch, Andreas Busjahn, Jeanette Schulz-Menger, Jens Jordan, Friedrich C Luft, Rainer Dietz, Martin W Bergmann, Sven Haufe, Florian von Knobelsdorff-Brenkenhoff, Heidrun Mehling, Ralf Wassmuth, Ines Münch, Andreas Busjahn, Jeanette Schulz-Menger, Jens Jordan, Friedrich C Luft, Rainer Dietz
Abstract
Aims: Low-dose epoetin-β improved neo-angiogenesis and cardiac regeneration in experimental models of ischaemic cardiomyopathy without raising haemoglobin. No clinical study has tested this approach to date.
Methods and results: We performed a randomized, placebo-controlled, double-blind, single-centre study of 35 IU/kg body weight epoetin-β given subcutaneously once weekly for 6 months started within 3 weeks after successful percutaneous coronary intervention (PCI). Patients were included if they presented with a lesion within the proximal segment of the left anterior descending artery, the right coronary artery, or circumflex and had symptomatic heart failure. Patients with ST-segment elevation due to an acute myocardial infarct were excluded. The outcome variables were measured at baseline and at 6 months. Primary outcome measure was individual change in ejection fraction; secondary outcome was safety, change in N-terminal pro-brain natriuretic peptide, and peak VO(2). Twenty-four patients completed the 6-month treatment course. No adverse event related to the treatment occurred. Low-dose epoetin-β following PCI significantly improved global ejection fraction as measured by echocardiography (EPO: ΔEF 5.2 ± 2.0%, P= 0.013; placebo: ΔEF 0.3 ± 1.6%, P= 0.851; P= 0.019 for the inter-group difference) and cardiac magnetic resonance (EPO: ΔEF 3.1 ± 1.6%, P= 0.124; placebo: -1.9 ± 1.2%, P= 0.167; P= 0.042 for the inter-group difference). N-terminal pro-brain natriuretic peptide levels decreased in both groups without significant inter-group differences. Peak VO(2) levels increased significantly by 3.9 ± 1.1% (P< 0.05) in the EPO group, whereas in the placebo group the increase did not reach statistical significance (Δpeak VO(2) 3.0 ± 1.6, P = ns). No significant difference regarding peak VO(2) was observed between the EPO and placebo groups.
Conclusions: Low-dose epoetin-β treatment following PCI is safe and feasible, and has possible beneficial effects on global ejection fraction and measures of exercise capacity. Extended low-dose epoetin-β treatment warrants further mechanistic studies as well as larger clinical trials.
Clinical trial registration information: NCT00568542.
Source: PubMed