Effect of beta-blockade and ACE inhibition on B-type natriuretic peptides in stable patients with systolic heart failure.
BACKGROUND
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 cardiovascular 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)).


CONCLUSIONS
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.
Rosenberg
Jens
J
Cardiology Department, Frederiksberg University Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark. cor@dadlnet.dk
Gustafsson
Finn
F
Remme
Willem J
WJ
Riegger
Günter A J
GA
Hildebrandt
Per Rossen
PR
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D011412:Propanolamines / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002227:Carbazoles; D010446:Peptide Fragments; D011412:Propanolamines; C109794:pro-brain natriuretic peptide (1-76); D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D004656:Enalapril