ASCEND-HF: Nesiritide Does Not Benefit Patients with Acute Heart Failure
Rapid approval of the drug for early symptom relief has proven to be unjustified.
Many drugs are introduced into practice with scant information about their effects on patient outcomes. Nesiritide, a recombinant B-type natiuretic peptide, was approved by the FDA in 2001 for acute heart failure (HF) based on studies showing that it reduced pulmonary-capillary wedge pressure and symptoms after a few hours of treatment. In 2005, after pooled-study analyses, questions were raised about risks associated with the drug. In response, ASCEND-HF, an industry-sponsored trial, was launched to determine the effects of nesiritide on dyspnea, HF readmission, death, and renal function. Investigators randomized 7141 patients hospitalized with acute HF to receive nesiritide or placebo for 24 to 168 hours. The co-primary endpoints were change in dyspnea at 6 and 24 hours and the composite of rehospitalization for HF and death at 30 days.
Neither primary endpoint differed significantly between the two groups. Thirty-day incidences of clinical outcomes with nesiritide compared with placebo were:
* Death or rehospitalization for HF: 9.4% vs. 10.1%
* Death: 3.6% vs. 4.0%
* Rehospitalization for HF: 6.0% vs. 6.1%
* Decrease in estimated glomerular filtration of >25%: 31.4% vs. 29.5%
* Hypotension: 26.6% vs. 15.3% (P<0.001)
O'Connor CM et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med 2011 Jul 7; 365:32.