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Follow-Up Serial Infusions of Nesiritide Trial - FUSION I
Description:
The goal of the trial was to evaluate the safety and tolerability of outpatient serial infusion of nesiritide compared with usual care in patients with decompensated congestive heart failure.
Study Design
Study Design:
Patients Enrolled: 210
NYHA Class: Class III 65%; Class IV 35%
Mean Follow Up: 16 weeks
Mean Patient Age: Mean age 67 years
Female: 30
Patient Populations:
Age ≥18 years, New York Heart Association class III or IV heart failure for ≥60 days before randomization, six-minute walk test result of <400 m, and ≥2 hospital admissions (or unscheduled outpatient visits requiring intravenous vasoactive treatment) for acutely decompensated heart failure within 12 months
Exclusions:
Systolic blood pressure <90 mm Hg, undergone placement of a biventricular pacemaker within 60 days, undergone placement of an implantable cardioverter defibrillator within 30 days, receiving long-term dialysis or likely to require dialysis during the four-month study period, evidence of acute myocardial infarction within 30 days, unable to complete a six-minute walk test, or had received or were awaiting an organ transplantation
Primary Endpoints:
Adverse events
Drug/Procedures Used:
Patients were randomized to: 1) usual care (n=69); 2) usual care plus low-dose nesiritide (1.0 µg/kg bolus and 0.005 µg/kg/min infusion for 4-6 hours) (n=72); or 3) usual care plus high-dose nesiritide (2.0 µg/kg bolus and 0.01 µg/kg/min infusion for 4-6 hours) (n=69). Nesiritide treatment was performed weekly for 12 weeks.
Concomitant Medications:
Diuretics (99%), beta-blockers (74%), angiotensin-converting enzyme inhibitors (61%), nitrates (48%), spironolactone (42%), and angiotensin II receptor blockers (19%)
Principal Findings:
In the nesiritide arms, 1,645 infusions were given for a mean total duration of 55 hours during the study. Intravenous inotropic agent was given during the study due to decompensated heart failure to 58% of patients in the usual care group compared with <2% in the nesiritide group. Infusion was stopped due to an adverse event in 6% of patients in the nesiritide arm (n=9), although discontinuation due to an adverse event was in <1% of infusions (n=11). During the 12-week study, there was no difference in adverse events by the treatment group. The most common adverse events were decompensated heart failure (42%), asymptomatic hypotension (18%), dyspnea (17%), and symptomatic hypotension (11%).
There was no difference in the composite endpoint of death or hospitalization by treatment group (58% usual care, 46% low-dose nesiritide [p=0.175], and 49% high-dose nesiritide [p=0.385]). Likewise, there was no difference in either individiual endpoint, for death (10% usual care, 8% low-dose nesiritide [p=0.692], 4% high-dose nesiritide [p=0.194]), or hospitalization (54% usual care, 44% low-dose nesiritide [p=0.314], 48% high-dose nesiritide [p=0.610]). Days alive and out of the hospital trended longer in the high-dose and low-dose nesiritide groups compared with the usual care group (79 days and 76 days vs. 74 days, p=0.159 for high-dose comparison, p=0.253 for low-dose comparison). Ejection fraction improved in all treatment groups, but only reached significance in the high-dose nesiritide group (p=0.03).
Interpretation:
Among patients with decompensated congestive heart failure, treatment with outpatient serial infusion of nesiritide was safe and tolerable compared with usual care. There was no difference in any of the clinical endpoints, although the study was not powered to detect such a difference. Larger studies are warranted to evaluate the efficacy of nesiritide in the outpatient setting for treatment of heart failure. Prior studies have evaluated nesiritide treatment during hospitalization for heart failure, but the present study is the first to evaluate its use in the outpatient setting.
References:
Yancy CW, Saltzberg MT, Berkowitz RL, et al. Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I trial). Am J Cardiol 2004;94:595-601.
Keywords: Heart Failure, Natriuretic Agents, Hypotension, Dyspnea, Hospitalization, Natriuretic Peptide, Brain
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