Nesiritide Administration in Patients Hospitalized for Acute Decompensated Heart Failure: Does Timing Matter?

Abstract

Background: It is unclear if early administration of nesiritide in patients with acute decompensated heart failure (ADHF) is associated with better patient reported or clinical outcomes. We sought to identify if time to study medication administration from hospital presentation is associated with these outcomes. Methods: Using data from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF), we examined the associations of time to study medication administration with moderate/marked improvement in dyspnea at 6 hours (7-point Likert scale) and 30-day all-cause death or re-hospitalization using multivariable lo- gistic regression. Furthermore, we examined if there is a differential effect of time to study medication administration on outcomes depending on treatment assignments (nesiritide vs. placebo). Linear splines (# and O 10 hours after admission) were ap- plied to time to study medication administration due to non-linear relationship with dyspnea improvement at 6 hours. Results: Of the 7003 patients, median time to study drug administration was 16.7 hours (25th, 75th percentiles 5 6.5, 23.1) with signif- icant regional variations (Figure). After adjusting for pre-randomization therapies and known predictors of outcomes, each hour delay in administrating study medication after the first 10 hours was associated with modestly reduced odds of achieving mod- erate/marked dyspnea improvement 6 hours after starting treatment (adjusted OR 0.98, 95% CI 0.98, 0.99; P!0.0001), but not 30-day outcomes (unadjusted OR 1.01, 95% CI 1.00, 1.02; P50.07). There was no significant differential effects of time to study medication administration on outcomes between treatment assignments (P values for interactions O0.1). Conclusion: Time to treatment with study medica- tion varied significantly across regions. Earlier administration of nesiritide was asso- ciated with modestly higher odds of moderate or marked dyspnea improvement at 6 hours but not 30-day outcomes. These findings may have implications for interpreta- tion of ADHF studies and future study designs.