TY - JOUR
T1 - Baseline and Serial Neurohormones in Patients With Congestive Heart Failure Treated With and Without Bucindolol
T2 - Results of the Neurohumoral Substudy of the Beta-Blocker Evaluation of Survival Study (BEST)
AU - Frantz, Robert P.
AU - Lowes, Brian D.
AU - Grayburn, Paul A.
AU - White, Michel
AU - Krause-Steinrauf, Heidi
AU - Krishnan, Vaishali
AU - Uyeda, Lauren
AU - Burnett, John C.
N1 - Funding Information:
BEST was sponsored by the Division of Epidemiology and Clinical Applications of the National Heart, Lung and Blood Institute and the Department of Veterans Affairs Cooperative Studies Program through an interagency agreement. Additional support was provided by Incara Pharmaceuticals Corporation, which also supplied bucindolol and placebo. The authors have no conflicts of interest or relevant financial disclosures to report.
PY - 2007/8
Y1 - 2007/8
N2 - 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). Methods and 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) ≤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.
AB - 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). Methods and 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) ≤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.
KW - CHF
KW - endothelin
KW - natriuretic peptides
KW - prognosis
KW - β-adrenergic antagonists
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U2 - 10.1016/j.cardfail.2007.03.007
DO - 10.1016/j.cardfail.2007.03.007
M3 - Article
C2 - 17675057
AN - SCOPUS:34547474630
SN - 1071-9164
VL - 13
SP - 437
EP - 444
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 6
ER -