1. Nesiritide in patients hospitalized for acute heart failure: does timing matter? Implication for future acute heart failure trials.
- Author
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Wong, Yee Weng, Mentz, Robert J., Felker, G.Michael, Ezekowitz, Justin, Pieper, Karen, Heizer, Gretchen, Hasselblad, Vic, Metra, Marco, O'Connor, Christopher M., Armstrong, Paul W., Starling, Randall C., and Hernandez, Adrian F.
- Subjects
NESIRITIDE ,HEART failure patients ,DRUG utilization ,DYSPNEA ,HEART failure treatment ,CLINICAL trials ,CAUSES of death ,HEART failure ,HOSPITAL care ,MEDICAL care ,MORTALITY ,PATIENTS ,PEPTIDE hormones ,WATER-electrolyte balance (Physiology) ,RANDOMIZED controlled trials ,TREATMENT effectiveness ,ACUTE diseases ,PATIENT readmissions ,ODDS ratio ,ARTHRITIS Impact Measurement Scales ,DISEASE complications ,THERAPEUTICS - 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. [ABSTRACT FROM AUTHOR]- Published
- 2016
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