Effect of Beta-blockade and ACE Inhibition on B-type Natriuretic Peptides in Stable Patients with Systolic Heart Failure Jens Rosenberg & Finn Gustafsson & Willem J. Remme & Günter A. J. Riegger & Per Rossen Hildebrandt Published online: 29 February 2008 # Springer Science + Business Media, LLC 2008 Abstract Introduction The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N- terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure. Methods Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+ enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardio- vascular hospitalisation. Results NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P<0.001), BNP 119 to 85 pg/ml (P<0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P=0.003), BNP 117 to 93 pg/ml (P=0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P=0.06), BNP 114 to 130 pg/ml (P=0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT- proBNP HR 1.018 95% CI (1.005–1.032), BNP 1.171 (1.088–1.260)). Conclusion Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT- proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition. Key words brain natriuretic peptide . adrenergic beta-antagonists . carvedilol . angiotensin-converting enzyme inhibitors . enalapril . prognosis . congestive heart failure Introduction Elevated plasma concentrations of B-type natriuretic pep- tides are important risk markers for death and hospital- isation in patients with heart failure (HF) [1, 2]. Indeed, therapeutic monitoring using these peptides has recently been suggested [3, 4]. Plasma levels of natriuretic peptides in patients with HF are lowered by treatment with various medications, such as ACE inhibitors [5], spironolactone [6, 7] and diuretics [8] and by non-pharmacological Cardiovasc Drugs Ther (2008) 22:305–311 DOI 10.1007/s10557-008-6099-6 The work originates from Cardiology Dept., Frederiksberg University Hospital, Frederiksberg, Denmark. J. Rosenberg (*) Cardiology Department, Frederiksberg University Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark e-mail: cor@dadlnet.dk F. Gustafsson Cardiology Department, Rigshospitalet, Copenhagen, Denmark W. J. Remme Sticares Cardiovascular Research Foundation, Oever 1-5, 3161GR Rhoon, The Netherlands G. A. J. Riegger Department of Internal Medicine 2, University of Regensburg, Regensburg, Germany P. R. Hildebrandt Cardiology Department, Roskilde County Hospital, Roskilde, Denmark