Follow-Up Serial Infusions of Nesiritide for the Management of Patients With Heart Failure - FUSION II
The goal of the trial was to evaluate treatment with serial outpatient nesiritide compared with placebo among patients with chronic decompensated heart failure (CDHF).
Patients Enrolled: 920
Mean Follow Up: 24 weeks
Mean Patient Age: Mean age, 65 years
Mean Ejection Fraction: Mean at baseline, 24.8%
CDHF with ≥2 heart failure hospitalizations in prior year; LVEF <40%; NYHA class IV heart failure; or NYHA class III heart failure with creatinine clearance <60 ml/min
Continuous or intermittent IV vasoactive drugs, or systolic blood pressure <90 mm Hg
All-cause death or CV or renal hospitalization
Days alive out of hospital, CV mortality, and quality of life
Patients were randomized 2:1 to serial outpatient nesiritide once or twice weekly (2 mcg/kg bolus and 0.01 mcg/kg/min infusion for 4-6 hours; n = 605) or placebo (n = 306) for 12 weeks. Following the 12-week active therapy, there was a 4-week taper and an additional 8-week follow-up. All patients were also treated with standard heart failure therapy per the treating physician.
At study entry, New York Heart Association (NYHA) class III was present in 47% of patients and class IV in 53% of patients. Heart failure was of ischemic etiology in 64% of patients. Mean left ventricular ejection fraction (LVEF) at baseline was 25%. An implantable cardioverter defibrillator had been implanted in 39% of patients, and 74% had a history of coronary artery disease. Slightly more than half of the patients were diabetics (51%).
There was no difference in the primary endpoint of all-cause death or cardiovascular (CV) or renal hospitalization between groups (36.7% for nesiritide vs. 36.8% for placebo, hazard ratio 1.03, p = 0.79). Among the components of the composite endpoint, there was no difference in either mortality (9.5% vs. 9.6%, respectively, p = 0.98) or CV or renal hospitalizations (32.9% vs. 33.9%, p = 0.95). Mean number of hospitalizations was 1.0 in the nesiritide group and 0.8 in the placebo group. There was no difference in quality-of-life measurements.
Drug-related adverse events occurred more frequently in the nesiritide group (42.0% vs. 27.5%, p < 0.01), primarily due to an increase in hypotension, but there was no difference in serious drug-related adverse events (8.0% vs. 8.2%). Frequency of increase in serum creatinine of >0.5 mg/dl was lower with nesiritide than placebo (32% vs. 39%, p < 0.05).
Among patients with CDHF, treatment with serial outpatient nesiritide for 12 weeks was not associated with a difference in the primary composite endpoint of death or CV or renal hospitalizations compared with placebo.
Nesiritide is currently approved for treatment of acute decompensated heart failure, but not for CDHF. Safety concerns have been raised regarding worsening renal function and mortality. While there was no efficacy demonstrated for nesiritide in the present study, there was also no safety hazard with respect to renal function or mortality in this setting, although it should be noted that the trial was relatively small.
Presented by Dr. Clyde W. Yancy at the American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.
Yancy CW, Krum H, Massie BM, et al. 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. Circ Heart Fail. 2008 May;1(1):9-16.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Coronary Artery Disease, Heart Failure, Natriuretic Agents, Hypotension, Stroke Volume, Creatinine, Hospitalization, Defibrillators, Implantable, Diabetes Mellitus, Natriuretic Peptide, Brain
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