Baseline and serial neurohormones in patients with congestive heart failure treated with and without bucindolol: results of the neurohumoral substudy of the Beta-Blocker Evaluation of Survival Study (BEST).
BACKGROUND
Serial neurohormones may serve as markers of efficacy of congestive heart failure (CHF) therapy. We measured serial plasma big-endothelin (Big-ET), ET-1, N-terminal atrial natriuretic peptide, and brain natriuretic peptide (BNP) in 206 patients randomized to bucindolol or placebo in Beta-Blocker Evaluation of Survival Trial (BEST).


RESULTS
Neurohormones were measured at baseline and 3 and 12 months. At baseline, BNP and Big-ET levels were greater in New York Heart Association (NYHA) Class IV than in Class III patients (median 122 pg/mL versus 447 pg/mL, P = .001; and 20.0 pg/mL versus 9.9 pg/mL, P = .003), and in patients with left ventricular ejection fraction (LVEF) < or = 20% compared with LVEF > 20% (median 211 pg/mL versus 99.1 pg/mL; and 12.9 pg/mL versus 8.0 pg/mL, both P = .003). Big-ET and BNP were the strongest predictors of the composite end point of CHF hospitalization or death. LVEF at 12 months correlated inversely with 12-month BNP levels (r = -0.41, P = .0001). Bucindolol had no effect on neurohormones except that bucindolol treated patients had lower Big-ET levels at 3 months than patients receiving placebo (median 9.1 pg/mL versus 10.9 pg/mL, P = .05). A decline in ET-1 was associated with increased risk of the composite endpoint.


CONCLUSIONS
Lack of effect of bucindolol on natriuretic peptide levels appears consistent with its overall lack of efficacy in BEST.
Division of Cardiovascular Diseases, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, Minnesota 55905, USA.
Robert P
RP
Frantz
Brian D
BD
Lowes
Paul A
PA
Grayburn
Michel
M
White
Heidi
H
Krause-Steinrauf
Vaishali
V
Krishnan
Lauren
L
Uyeda
John C
JC
Burnett
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D016232:Endothelins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011412:Propanolamines / Q000627:therapeutic use*; D011863:Radioimmunoassay; D013318:Stroke Volume; D015996:Survival Rate; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D019332:Endothelin-1; D016232:Endothelins; D011412:Propanolamines; C075556:big-endothelin (1-22); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C024307:bucindolol