Nesiritide Infusions for the Management of Decompensated Heart Failure -- Safety and Efficacy Results of the FUSION II Trial

Luis Gruberg, MD, FACC

Disclosures

June 12, 2007

Nesiritide, a recombinant form of human B-type natriuretic peptide, is an intravenous treatment that is US Food and Drug Administration (FDA)-approved for patients with acutely decompensated heart failure who have dyspnea at rest or with minimal activity.

The Follow-Up Serial Infusions of Nesiritide for the Management of Patients With Heart Failure II (FUSION II) trial analyzed the safety and efficacy of serial infusion of nesiritide in patients with advanced heart failure.

FUSION II was a placebo-controlled, double-blind trial that randomized patients in a 2:1 ratio to receive nesiritide bolus (2 microgram [mcg]/kg) followed by a 4- to 6-hour infusion of 0.01 mcg/kg/minute or matching placebo administered once or twice weekly for 12 weeks.

Patients with a left ventricular ejection fraction ≤ 40%, more than 2 heart failure hospitalizations or equivalent within a year, New York Heart Association class II or IV on optimal chronic heart failure therapy were included in the study. Patients with a systolic blood pressure < 90 mm Hg, on ≥ 2 vasoactive infusions within the last 30 days, and on chronic or expected dialysis were excluded from enrollment.

Primary endpoint: Time to all-cause death or first cardiovascular or renal hospitalization through week 12.

Secondary endpoints:

  • Number of cardiovascular and/or renal hospitalizations adjusted for observation period duration;

  • Days alive and out of hospital;

  • Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score; and

  • Time to cardiovascular death.

A total of 911 patients were randomized to placebo (n = 306) or nesiritide (n = 605). Baseline characteristics of patients were well balanced between the 2 groups, and all patients were on excellent background medical therapy ( Table 1 ).

The composite primary endpoint through week 12 -- all-cause mortality and cardiovascular/renal hospitalization -- was identical in the placebo and nesiritide arms (37%). There was also no difference in the rate of secondary endpoints between the 2 groups ( Table 2 ). The results remained consistent in all subgroups studied.

  1. In this large patient population with advanced heart failure, there is no evidence of drug-induced renal harm compared with placebo with serial infusion of nesiritide, and there is no evidence of increased mortality at prespecified endpoints.

  2. However, serial infusions of nesiritide did not result in a demonstrable clinical benefit over intensive outpatient management of decompensated heart failure.

Unfortunately, the results of this study showed that treatment with nesiritide did not improve the outcomes of patients with decompensated heart failure. However, treatment with nesiritide was not associated with increased mortality or deterioration in renal failure, a concern that has been raised repeatedly with this drug.

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