Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: results of the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial

Abstract

Background: Patients with American College of Cardiology/American Heart Association stage C/D heart failure experience substantial morbidity and mortality, but available interventions beyond standard medical and device therapies are limited. Nesiritide relieves dyspnea and reduces pulmonary congestion, but its risk profile is uncertain. Pilot data suggested a potential benefit of nesiritide given as serial outpatient infusions.

Methods and results: The Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial was a randomized, double-blind, placebo-controlled trial of outpatient serial nesiritide infusions for patients with American College of Cardiology/American Heart Association stage C/D heart failure. Patients with 2 recent heart failure hospitalizations, ejection fraction <40%, and New York Heart Association class IV symptoms, or New York Heart Association class III symptoms with creatinine clearance <60 mL/min, were randomized to nesiritide (2-microg/kg bolus plus 0.01-microg/kg-per-minute infusion for 4 to 6 hours) or matching placebo, once or twice weekly for 12 weeks. All patients were treated to optimal goals with evidence-based medical/device therapy facilitated by careful disease management during the study. The primary end point was time to all-cause death or cardiovascular or renal hospitalization at 12 weeks. A total of 911 patients were randomized and treated. The primary end point occurred in 36.8% and 36.7% of the placebo and nesiritide groups, respectively (hazard ratio, 1.03; 95% confidence interval, 0.82 to 1.3; log-rank test P=0.79). There were no statistically significant differences between groups in any of the secondary end points, including the number of cardiovascular or renal hospitalizations, the number of days alive and out of the hospital, change in Kansas City Cardiomyopathy Questionnaire score, or cardiovascular death. Adverse events were similar between groups; nesiritide was associated with more hypotension but less predefined worsening renal function.

Conclusions: Serial outpatient nesiritide infusions do not provide a demonstrable clinical benefit over intensive outpatient management of patients with advanced American College of Cardiology/American Heart Association stage C/D heart failure.

Trial registration: ClinicalTrials.gov NCT00091520.