Acute decompensated heart failure (ADHF) is a growing health problem due to its poor prognosis, increasingly frequent reason for hospitalization, and high cost to the health care system.1-4 Furthermore, about one-fifth of those hospitalized were rehospitalized within 30 days.5 The syndrome of ADHF predominantly features the development of dyspnea and other symptoms usually due to volume overload and/or hypoperfusion.6,7 Nesiritide is an intravenous recombinant B-type natriuretic peptide (BNP) indicated for the treatment of patients with ADHF who have dyspnea at rest or with minimal activity.8 Two meta-analyses suggest that nesiritide is associated with increased risk of worsening renal function and an increase in mortality.9,10
To clarify the safety and efficacy of nesiritide in addition to standard therapy, the ASCEND-HF trial was conducted. The ASCEND-HF was a large, randomized, double-blind, placebo-controlled trial that included a little over 7,000 patients who were experiencing dyspnea at rest or with minimal activity at the time of randomization. Eligible patients were randomly assigned in a 1:1 ratio to receive nesiritide or placebo. The nesiritide group was recommended an optional intravenous bolus of 2 µg/kg nesiritide, then was administered a continuous infusion of nesiritide at 0.010 µg/kg/min for 24 hours or more for up to 7 days. The two co-primary end points were the change in self-reported dyspnea at 6 and 24 hours after the study-drug initiation and the composite end point of rehospitalization for heart failure and death from any cause during the period from randomization to day 30.11
When compared to placebo, the nesiritide group showed no significant difference in the improvement of dyspnea at either 6 hours (44.5% vs. 42.1%, P=0.03) or 24 hours (68.2 vs. 66.1%, P=0.007). There was also no difference in the rehospitalization for heart failure or death from any cause during the 30 days with patients in the nesiritide group as compared to patients in the placebo group (9.4% vs. 10.1%, P=0.31). The occurrence of hypotension was significantly greater in the nesiritide group than in the placebo group (26.6% vs. 15.3%, P<0.001, number needed to harm = 9), irrespective of whether the hypotension was symptomatic or asymptomatic. No significant differences were observed in serious adverse events.11
The Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial,12 which formed the basis for the Food and Drug Administration’s approval of nesiritide, included a total of 498 patients. Patients receiving nesiritide showed improvement in self-reported dyspnea from baseline to 3 hours after the start of drug administration. Nesiritide offered no significant difference in decreasing rehospitalization or incidence of death at 30 days.
The ASCEND-HF trial provides hard evidence in the lack of clinical benefit in the use of nesiritide in addition to standard therapy in ADHF patients. Importantly, the number needed to harm for hypotension was 9. When choosing medication therapy, the risks and benefits ratio should be in favor of the benefits to provide optimal patient care. In the case of nesiritide, the lack of benefit combined with its greater risk for causing hypotension clearly denotes that the use of this medicine should not be ...