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Eur J Heart Fail. 2016 Jun;18(6):684-92. doi: 10.1002/ejhf.487. Epub 2016 Jan 27.

Nesiritide in patients hospitalized for acute heart failure: does timing matter? Implication for future acute heart failure trials.

Author information

1
Heart Lung Institute, The Prince Charles Hospital, Chermside, QLD, Australia.
2
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
3
University of Alberta, Edmonton, Alberta, Canada.
4
Cardiology, The Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
5
Cleveland Clinic Foundation, Cleveland, OH, USA.

Abstract

AIMS:

It remains unclear if early administration of i.v. nesiritide in patients hospitalized with acute heart failure (AHF) is associated with improved clinical outcomes.

METHODS AND RESULTS:

We analysed data from 7007 patients enrolled in ASCEND-HF to examine the associations between time to treatment with study medication (nesiritide or placebo) and clinical endpoints: (i) moderate to marked dyspnoea relief on a 7-point Likert scale at 6 h; (ii) 30-day all-cause mortality or re-hospitalization; and (iii) 30-day all-cause mortality. The median time to study drug administration was 16.7 h (25th, 75th percentiles = 6.5, 23.1), with significant regional variation (e.g. median of 13.0 h in Asia-Pacific vs. 18.4 h in North America). After risk adjustment, each hour delay in study medication after the first 10 h from initial hospital presentation was associated with modestly reduced odds of dyspnoea relief [(adjusted odds ratio (OR) 0.98, 95% confidence interval (CI) 0.98-0.99; P < 0.0001]. Every hour delay in study medication was associated with modestly higher all-cause mortality or re-hospitalization (unadjusted OR 1.01, 95% CI 1.01-1.02; P < 0.001) due to pre-randomization therapies and known predictors of 30-day outcomes (adjusted P = 0.12). There was no significant association between time to study drug and all-cause mortality (P > 0.08).

CONCLUSION:

In a large international AHF trial, time to treatment with study medication varied markedly across regions. Earlier administration of study medication was associated with modestly better dyspnoea relief, but not 30-day clinical outcomes. The association between timing of treatment with study medication and study endpoints may have implications for the interpretation of AHF studies and future trial design.

KEYWORDS:

Acute heart failure; Clinical trials; Nesiritide

PMID:
26817735
DOI:
10.1002/ejhf.487
[Indexed for MEDLINE]
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