Nesiritide not effective for acute heart failure, study finds

Nesiritide is not an effective treatment for acute decompensated heart failure, according to a new controlled trial.

The study randomized more than 7,000 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. End points were change in dyspnea and rehospitalization or death within 30 days. The results were published in the July 7 New England Journal of Medicine.

Patients taking nesiritide reported improved dyspnea at both six hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but these differences did not meet the study's prespecified minimum for statistical significance. Very little difference was seen between the groups in rehospitalization or death (9.4% on nesiritide vs. 10.1% on placebo, P=0.31), death at 30 days (3.6% on nesiritide vs. 4.0% on placebo) or worsening renal function (defined as a >25% decrease in estimated glomerular filtration rate, 31.4% on nesiritide vs. 29.5% on placebo, P=0.11). However, nesiritide did significantly increase rates of hypotension in patients who took it: 26.6% versus 15.3% (P<0.001).

Based on the results, study authors concluded that “nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure.” They noted that their findings are consistent with results of the trial that led to FDA approval of nesiritide a decade ago. That study included about 500 patients and showed that the drug significantly improved dyspnea at 3 hours, but made little difference at 24 hours

The current study contradicted widespread assumptions about both the effectiveness of nesiritide in relieving dyspnea and its potential to harm patients by reducing survival and renal function, the authors noted. The results show the need for rigorously designed, adequately powered trials of new medications, the authors said. An accompanying editorial expanded on this conclusion, saying that “the FDA should be provided the full regulatory authority to require definitive trials and withdraw a drug if the sponsor does not conduct a far-reaching clinical end-point trial.”