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Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.

Abstract：

BACKGROUND:Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent. METHODS AND RESULTS:Systemic venous norepinephrine was measured at baseline, 3 months, and 12 months in the beta-Blocker Evaluation of Survival Trial (BEST), which compared placebo treatment with the beta-blocker/sympatholytic agent bucindolol. Baseline norepinephrine level was associated with a progressive increase in rates of death or death plus CHF hospitalization that was independent of treatment group. On multivariate analysis, baseline norepinephrine was also a highly significant (P<0.001) independent predictor of death. In contrast, the relation of the change in norepinephrine at 3 months to subsequent clinical outcomes was complex and treatment group-dependent. In the placebo-treated group but not in the bucindolol-treated group, marked norepinephrine increase at 3 months was associated with increased subsequent risks of death or death plus CHF hospitalization. In the bucindolol-treated group but not in the placebo-treated group, the 1st quartile of marked norepinephrine reduction was associated with an increased mortality risk. A likelihood-based method indicated that 18% of the bucindolol group but only 1% of the placebo group were at an increased risk for death related to marked reduction in norepinephrine at 3 months. CONCLUSIONS:In BEST, a subset of patients treated with bucindolol had an increased risk of death as the result of sympatholysis, which compromised the efficacy of this third-generation beta-blocker.

journal_name

Circulation

journal_title

Circulation

authors

Bristow MR,Krause-Steinrauf H,Nuzzo R,Liang CS,Lindenfeld J,Lowes BD,Hattler B,Abraham WT,Olson L,Krueger S,Thaneemit-Chen S,Hare JM,Loeb HS,Domanski MJ,Eichhorn EJ,Zelis R,Lavori P

doi

10.1161/01.CIR.0000141297.50027.A4

subject

Has Abstract

pub_date

2004-09-14 00:00:00

pages

1437-42

issue

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000141297.50027.A4

journal_volume

110

pub_type

临床试验,杂志文章,多中心研究,随机对照试验

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Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.