Serial infusions of nesiritide have no apparent benefit for outpatients with chronic decompensated heart failure who already receive excellent care, but there is no evidence of adverse effects on renal failure or risk of death, according to results from a late-breaking trial presented at the scientific session of the American College of Cardiology.

For patients with stage D or chronic decompensated heart failure, hospitalization is frequent and treatment options are limited. The FUSION II trial (Follow-Up Serial Infusions of Nesiritide in Advanced Heart Failure) tested the benefit of a novel drug infusion regimen of serial administration of nesiritide versus placebo in outpatients with advanced heart failure.

Nesiritide, a recombinant form of human B-type natriuretic peptide, is approved in the United States for the treatment of acute decompensated heart failure, but questions regarding the safety of nesiritide have been raised. Currently, it is primarily administered to hospitalized patients, but the current study tested the potential benefit and safety of outpatient treatment to improve the natural history of patients with chronic heart failure.

FUSION II was a randomized, double-blind, placebo-controlled study with 920 patients. The trial was designed to prospectively evaluate efficacy and safety of serial outpatient infusions; it followed promising results from FUSION I. Patients in FUSION II were randomized to nesiritide 2 mcg/kg bolus and 0.01 mcg/kg/min for 4-6 hours (605 patients) or matching placebo (306 patients) once or twice weekly for 12 weeks, with a 4-week taper and 8-week follow-up.

Although the primary results on all-cause mortality and cardiorenal hospitalizations were neutral, there was no evidence of renal harm or excess mortality attributed to use of nesiritide.

Background therapy was excellent with high compliance regarding standard, evidence-based medical and device therapy, along with an extraordinary program of precise disease management. The event rates in FUSION II were 33 percent lower than that seen in FUSION I, likely due to the excellent background therapy and medical care. Of note, outpatient inotropic support was allowed in FUSION I, but not in FUSION II.

In that context, the primary effect of NES infusion therapy was neutral, as the benefit of background therapy was substantially greater than that seen in the first trial. Regarding the questions of safety that persist with the use of nesiritide, this study demonstrated no evidence of renal harm or excess mortality.

“This is the largest heart failure trial to date in patients with stage D heart failure, the least stable of all heart failure patients who are in dire need of novel treatment methods. Serial administration of outpatient nesiritide infusions was not shown to be significantly beneficial in the context of excellent care. The lesson learned here is that appropriate use of evidence-based medical and device therapy, as well as avoidance of non-evidence based therapies done in concert with highly sophisticated and rigorous follow-up, is beneficial even in advanced disease,” said Clyde W. Yancy, MD, of Baylor University Medical Center at Dallas, and lead study author. “Practitioners should follow the current guidelines and strive to achieve optimal medical and device therapy in this patient population. It is reassuring to note that the safety data regarding nesiritide, obtained in this vulnerable patient population who have advanced heart failure, are neutral.”