Effects of nesiritide and predictors of urine output in acute decompensated heart failure: results from ASCEND-HF (acute study of clinical effectiveness of nesiritide and decompensated heart failure)

Objectives: This study sought to determine if nesiritide increases diuresis in congestive heart failure patients.

Background: In the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure), 7,141 patients hospitalized with acute decompensated heart failure (ADHF) were randomized to receive nesiritide or placebo for 24 to 168 h, in addition to standard care. There were minimal effects of nesiritide on survival, future hospitalizations, and symptoms. However, whether or not nesiritide increases diuresis in ADHF patients is unknown.

Methods: Urine output was measured in 5,864 subjects; of these, 5,320 received loop diuretics and had dose data recorded. Loop diuretics other than furosemide were converted to furosemide equivalent doses. A total of 4,881 patients had complete data. We used logistic regression models to identify the impact of nesiritide on urine output and the factors associated with high urine output.

Results: Median (25th, 75th percentiles) 24-h urine output was 2,280 (1,550, 3,280) ml with nesiritide and 2,200 (1,550, 3,200) ml with placebo (p = NS). Loop diuretic dose (furosemide equivalent) was 80 (40, 140) mg with both nesiritide and placebo. Diuretic dose was a strong predictor of urine output. Other independent predictors included: male sex, greater body mass index, higher diastolic blood pressure, elevated jugular venous pressure, recent weight gain, and lower blood urea nitrogen. The addition of nesiritide did not change urine output. None of the interaction terms between nesiritide and predictors affected the urine output prediction.

Conclusions: Nesiritide did not increase urine output in patients with ADHF. Higher diuretic dose was a strong predictor of higher urine output, but neurohormonal activation (as evidenced by blood urea nitrogen concentration) and lower blood pressure limited diuresis.