Nesiritide is approved in the United States for early relief of dyspnea in patients with
acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity
and the mortality associated with this agent.
We randomly assigned 7141 patients who were hospitalized with acute heart failure to
receive either nesiritide or placebo for 24 to 168 hours in addition to standard care.
Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on
a 7-point Likert scale, and the composite end point of rehospitalization for heart failure
or death within 30 days.
Patients randomly assigned to nesiritide, as compared with those assigned to placebo,
more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5
vs. 42.1 , P = 0.03) and 24 hours (68.2 vs. 66.1 , P = 0.007), but the prespecified level
for significance (Pa??0.005 for both assessments or Pa??0.0025 for either) was not met.
The rate of rehospitalization for heart failure or death from any cause within 30 days
was 9.4 in the nesiritide group versus 10.1 in the placebo group (absolute difference,
a??0.7 percentage points; 95 confidence interval [CI], a??2.1 to 0.7; P = 0.31).
There were no significant differences in rates of death from any cause at 30 days
(3.6 with nesiritide vs. 4.0 with placebo; absolute difference, a??0.4 percentage
points; 95 CI, a??1.3 to 0.5) or rates of worsening renal function, defined by more
than a 25 decrease in the estimated glomerular filtration rate (31.4 vs. 29.5 ;
odds ratio, 1.09; 95 CI, 0.98 to 1.21; P = 0.11).
Nesiritide was not associated with an increase or a decrease in the rate of death and
rehospitalization and had a small, nonsignificant effect on dyspnea when used in
combination with other therapies. It was not associated with a worsening of renal
function, but it was associated with an increase in rates of hypotension. On the basis