CardioExchange Archive

In a new analysis of data from the ASCEND-HF trial, investigators found that nesiritide did not increase urine output in patients with acute decompensated heart failure (ADHF). CardioExchange Editor-in-Chief Harlan Krumholz interviews lead investigator Stephen Gottlieb about the study, which was recently published in the Journal of the American College of Cardiology.

Krumholz: You found that nesiritide did not increase urine output. Many clinicians would have bet that it did increase diuresis on the basis of their clinical experience. Did the result surprise you?

Gottlieb: In my clinical experience, I have not seen improved diuresis with nesiritide, but certainly many clinicians believe that it is very effective.  I wonder whether this reflects treatment of different patients.  Perhaps severe chronic HF patients don’t respond, while patients with acute HF or rapid decrease in brain natriuretic peptide (e.g., after total artificial heart implant) do respond. This may be worth investigating, but one would want to know if patients who did respond to nesiritide derived benefit from it (or would they also respond to conventional diuretics).

Krumholz:  What does ASCEND-HF tell us about the importance of doing outcomes trials to test interventions that are approved based on surrogate endpoints? Did it change your thoughts at all?

Gottlieb: I believe that ASCEND-HF answered many clinically important outcomes and, thus, was an important study.  The results of ASCEND-HF showed no improvement in what doctors and patients care about — mortality, hospitalizations, renal function, and urine output.  Whether FDA approval for short-term dyspnea improvement is appropriate is a different question that ASCEND-HF cannot answer.

Krumholz: What does your study tell clinicians about their care of patients with HF? Should we be using diuretics in higher doses for patients with ADHF?

Gottlieb: Not all HF patients need diuresis, but in those who do (probably a majority of those hospitalized) I believe that reluctance to use high doses of furosemide has limited success in diuresis.  This is consistent with the excellent diuresis seen in the aggressive protocols of CARESS.