In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients Hospitalized for Worsening Heart Failure. Insights From the EVEREST Trial

Alicia Mecklai; Haris Subačius; Marvin A. Konstam; Mihai Gheorghiade; Javed Butler; Andrew P. Ambrosy; Stuart D. Katz

doi:10.1016/j.jchf.2016.02.008

In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients Hospitalized for Worsening Heart Failure. Insights From the EVEREST Trial

Alicia Mecklai, Haris Subačius, Marvin A. Konstam, Mihai Gheorghiade, Javed Butler, Andrew P. Ambrosy, Stuart D. Katz^*

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Objectives: The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF). Background: Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for HF, but the association between loop diuretic agent dose response and post-discharge outcomes has not been well characterized. Methods: Cox proportional hazards models were used to estimate the association among average loop diuretic agent dose, congestion status at discharge, and 30-day post-discharge all-cause mortality and HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) study. Results: In univariate analysis, subjects exposed to high-dose diuretic agents (≥160 mg/day) had greater risk for the combined outcome than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio: 2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for pre-specified covariates of disease severity, the association between diuretic agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical assessments of volume status, 2,063 (69%) had little or no congestion at hospital discharge. Congestion status at hospital discharge did not modify the association between diuretic agent exposure and the combined endpoint (p for interaction = 0.84). Conclusions: Short-term diuretic agent exposure during hospital treatment for worsening HF was not an independent predictor of 30-day all-cause mortality and HF rehospitalization in multivariate analysis. Congestion status at discharge did not modify the association between diuretic agent dose and clinical outcomes.

Original language	English (US)
Pages (from-to)	580-588
Number of pages	9
Journal	JACC: Heart Failure
Volume	4
Issue number	7
DOIs	https://doi.org/10.1016/j.jchf.2016.02.008
State	Published - Jul 1 2016

Keywords

Acute heart failure
Loop diuretic agents
Outcomes

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jchf.2016.02.008

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@article{dd70d63bff0d42588919049e2ca78c50,

title = "In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients Hospitalized for Worsening Heart Failure. Insights From the EVEREST Trial",

abstract = "Objectives: The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF). Background: Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for HF, but the association between loop diuretic agent dose response and post-discharge outcomes has not been well characterized. Methods: Cox proportional hazards models were used to estimate the association among average loop diuretic agent dose, congestion status at discharge, and 30-day post-discharge all-cause mortality and HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) study. Results: In univariate analysis, subjects exposed to high-dose diuretic agents (≥160 mg/day) had greater risk for the combined outcome than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio: 2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for pre-specified covariates of disease severity, the association between diuretic agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical assessments of volume status, 2,063 (69%) had little or no congestion at hospital discharge. Congestion status at hospital discharge did not modify the association between diuretic agent exposure and the combined endpoint (p for interaction = 0.84). Conclusions: Short-term diuretic agent exposure during hospital treatment for worsening HF was not an independent predictor of 30-day all-cause mortality and HF rehospitalization in multivariate analysis. Congestion status at discharge did not modify the association between diuretic agent dose and clinical outcomes.",

keywords = "Acute heart failure, Loop diuretic agents, Outcomes",

author = "Alicia Mecklai and Haris Suba{\v c}ius and Konstam, {Marvin A.} and Mihai Gheorghiade and Javed Butler and Ambrosy, {Andrew P.} and Katz, {Stuart D.}",

note = "Funding Information: The EVEREST program was funded by Otsuka, and database management was provided by the trial sponsor. This work was supported in part by grant NIH/NCATS UL1 TR000038 from the National Center for Research Resources, National Institutes of Health. Dr. Katz has served as a member of the speakers bureau for Otsuka America Pharmaceuticals. Dr. Konstam has received research support from Otsuka America Pharmaceuticals. Dr. Gheorghiade has served as a consultant for Otsuka America Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2016 American College of Cardiology Foundation.",

year = "2016",

month = jul,

day = "1",

doi = "10.1016/j.jchf.2016.02.008",

language = "English (US)",

volume = "4",

pages = "580--588",

journal = "JACC: Heart Failure",

issn = "2213-1779",

publisher = "Elsevier BV",

number = "7",

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TY - JOUR

T1 - In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients Hospitalized for Worsening Heart Failure. Insights From the EVEREST Trial

AU - Mecklai, Alicia

AU - Subačius, Haris

AU - Konstam, Marvin A.

AU - Gheorghiade, Mihai

AU - Butler, Javed

AU - Ambrosy, Andrew P.

AU - Katz, Stuart D.

N1 - Funding Information: The EVEREST program was funded by Otsuka, and database management was provided by the trial sponsor. This work was supported in part by grant NIH/NCATS UL1 TR000038 from the National Center for Research Resources, National Institutes of Health. Dr. Katz has served as a member of the speakers bureau for Otsuka America Pharmaceuticals. Dr. Konstam has received research support from Otsuka America Pharmaceuticals. Dr. Gheorghiade has served as a consultant for Otsuka America Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2016 American College of Cardiology Foundation.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Objectives: The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF). Background: Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for HF, but the association between loop diuretic agent dose response and post-discharge outcomes has not been well characterized. Methods: Cox proportional hazards models were used to estimate the association among average loop diuretic agent dose, congestion status at discharge, and 30-day post-discharge all-cause mortality and HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) study. Results: In univariate analysis, subjects exposed to high-dose diuretic agents (≥160 mg/day) had greater risk for the combined outcome than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio: 2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for pre-specified covariates of disease severity, the association between diuretic agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical assessments of volume status, 2,063 (69%) had little or no congestion at hospital discharge. Congestion status at hospital discharge did not modify the association between diuretic agent exposure and the combined endpoint (p for interaction = 0.84). Conclusions: Short-term diuretic agent exposure during hospital treatment for worsening HF was not an independent predictor of 30-day all-cause mortality and HF rehospitalization in multivariate analysis. Congestion status at discharge did not modify the association between diuretic agent dose and clinical outcomes.

AB - Objectives: The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF). Background: Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for HF, but the association between loop diuretic agent dose response and post-discharge outcomes has not been well characterized. Methods: Cox proportional hazards models were used to estimate the association among average loop diuretic agent dose, congestion status at discharge, and 30-day post-discharge all-cause mortality and HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) study. Results: In univariate analysis, subjects exposed to high-dose diuretic agents (≥160 mg/day) had greater risk for the combined outcome than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio: 2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for pre-specified covariates of disease severity, the association between diuretic agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical assessments of volume status, 2,063 (69%) had little or no congestion at hospital discharge. Congestion status at hospital discharge did not modify the association between diuretic agent exposure and the combined endpoint (p for interaction = 0.84). Conclusions: Short-term diuretic agent exposure during hospital treatment for worsening HF was not an independent predictor of 30-day all-cause mortality and HF rehospitalization in multivariate analysis. Congestion status at discharge did not modify the association between diuretic agent dose and clinical outcomes.

KW - Acute heart failure

KW - Loop diuretic agents

KW - Outcomes

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In-Hospital Diuretic Agent Use and Post-Discharge Clinical Outcomes in Patients Hospitalized for Worsening Heart Failure. Insights From the EVEREST Trial

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