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Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.
Circulation. 2004 Sep 14; 110(11):1437-42.Circ

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.

Authors+Show Affiliations

University of Colorado Health Sciences Center, Division of Cardiology, Denver, Colo 80262, USA. michael.Bristow@uchsc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15337700

Citation

Bristow, M R., et al. "Effect of Baseline or Changes in Adrenergic Activity On Clinical Outcomes in the Beta-blocker Evaluation of Survival Trial." Circulation, vol. 110, no. 11, 2004, pp. 1437-42.
Bristow MR, Krause-Steinrauf H, Nuzzo R, et al. Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial. Circulation. 2004;110(11):1437-42.
Bristow, M. R., Krause-Steinrauf, H., Nuzzo, R., Liang, C. S., Lindenfeld, J., Lowes, B. D., Hattler, B., Abraham, W. T., Olson, L., Krueger, S., Thaneemit-Chen, S., Hare, J. M., Loeb, H. S., Domanski, M. J., Eichhorn, E. J., Zelis, R., & Lavori, P. (2004). Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial. Circulation, 110(11), 1437-42.
Bristow MR, et al. Effect of Baseline or Changes in Adrenergic Activity On Clinical Outcomes in the Beta-blocker Evaluation of Survival Trial. Circulation. 2004 Sep 14;110(11):1437-42. PubMed PMID: 15337700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial. AU - Bristow,M R, AU - Krause-Steinrauf,H, AU - Nuzzo,R, AU - Liang,Cheng-Seng, AU - Lindenfeld,J, AU - Lowes,B D, AU - Hattler,B, AU - Abraham,W T, AU - Olson,L, AU - Krueger,S, AU - Thaneemit-Chen,S, AU - Hare,J M, AU - Loeb,H S, AU - Domanski,M J, AU - Eichhorn,E J, AU - Zelis,R, AU - Lavori,P, Y1 - 2004/08/30/ PY - 2004/9/1/pubmed PY - 2005/4/12/medline PY - 2004/9/1/entrez SP - 1437 EP - 42 JF - Circulation JO - Circulation VL - 110 IS - 11 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15337700/Effect_of_baseline_or_changes_in_adrenergic_activity_on_clinical_outcomes_in_the_beta_blocker_evaluation_of_survival_trial_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000141297.50027.A4?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -