
FUSION: Follow Up Serial Infusions of Nesiritide
Nesiritide is safe and well tolerated when administered as weekly infusions on an outpatient basis in patients with advanced congestive heart failure (CHF) who are at high risk of hospitalization, according to the results of the Follow-Up Serial Infusions of Nesiritide (FUSION) trial. The FUSION data also suggest that compared with standard care, nesiritide administered in this setting may confer additional benefits, such as fewer deaths and hospitalizations and improvement in New York Heart Association (NYHA) heart failure class and overall clinical status.
Nesiritide, a recombinant form of human B-type natriuretic peptide, is approved in the United States for the treatment of acutely decompensated CHF in patients with dyspnea at rest or with minimal activity. It is currently administered in hospitalized patients. If the benefits seen in FUSION on clinical outcomes such as mortality and hospitalizations are replicated in a larger trial, however, nesiritide has the potential to become an effective outpatient treatment for hundreds of thousands of patients with advanced chronic heart failure, according to FUSION investigator Clyde W Yancy, MD (University of Texas Southwestern Medical Center, Dallas).
FUSION was a multicenter, randomized, open-label study in which 210 CHF patients at high risk of hospitalization were randomized to 1 of 3 treatment arms: standard care (consisting of long-term cardiac medications with or without intravenous inotropes) or serial infusions of either 0.005 or 0.01 mcg/kg/min of nesiritide in addition to their usual long-term cardiac medications, excluding intravenous inotropes. Patients were further classified as low or high risk on the basis of the following 7 criteria:
Patients with ≥ 4 positive criteria were considered high risk. All patients had weekly outpatient visits for 12 weeks and nesiritide patients received a 4- to 6-hr infusion at each weekly visit. Patients were observed for an additional period of 4 weeks after completion of the 3-month treatment period.
No significant difference was seen between treatment groups with regard to the frequency of serious adverse events (SAEs), and no adverse event (eg, heart failure, hypotension, renal AEs) occurred more frequently in the nesiritide groups. Out of a total of 1645 nesiritide infusions administered, only 11 (1%) were discontinued due to an AE.
Through 12 weeks, more patients in the standard-treatment group died or were hospitalized than in the nesiritide-treated groups (58% vs 48%, P = .185). Ten percent of standard-care patients died compared with 6% of nesiritide patients (P = .314), and 54% vs 46%, respectively, were hospitalized (P = .378) over the same period. Patients classified as high risk and treated with nesiritide showed statistically significant reductions in death and all-cause hospitalization compared with high-risk patients on standard care (52% vs 78%, P < .038). The same group also had higher survival rates and were out of hospital longer (mean 75.0 days vs 67.2 days, P = .027). Among the high-risk patients, 5% of nesiritide patients died over the course of the 12-week treatment period compared with 17% of high-risk patients on standard care.
A larger study is planned to assess the efficacy of serial outpatient infusions of nesiritide for several months in reducing death and hospitalizations in patients with chronic CHF who are at high risk for hospitalization.
Reference
Nesiritide is safe and well tolerated when administered as weekly infusions on an outpatient basis in patients with advanced congestive heart failure (CHF) who are at high risk of hospitalization, according to the results of the Follow-Up Serial Infusions of Nesiritide (FUSION) trial. The FUSION data also suggest that compared with standard care, nesiritide administered in this setting may confer additional benefits, such as fewer deaths and hospitalizations and improvement in New York Heart Association (NYHA) heart failure class and overall clinical status.
Nesiritide, a recombinant form of human B-type natriuretic peptide, is approved in the United States for the treatment of acutely decompensated CHF in patients with dyspnea at rest or with minimal activity. It is currently administered in hospitalized patients. If the benefits seen in FUSION on clinical outcomes such as mortality and hospitalizations are replicated in a larger trial, however, nesiritide has the potential to become an effective outpatient treatment for hundreds of thousands of patients with advanced chronic heart failure, according to FUSION investigator Clyde W Yancy, MD (University of Texas Southwestern Medical Center, Dallas).
FUSION was a multicenter, randomized, open-label study in which 210 CHF patients at high risk of hospitalization were randomized to 1 of 3 treatment arms: standard care (consisting of long-term cardiac medications with or without intravenous inotropes) or serial infusions of either 0.005 or 0.01 mcg/kg/min of nesiritide in addition to their usual long-term cardiac medications, excluding intravenous inotropes. Patients were further classified as low or high risk on the basis of the following 7 criteria:
Serum creatinine ≥ 2.0 mg/L within 30 days;
NYHA class IV; ≥ 65 years old;
History of sustained ventricular tachycardia;
Ischemic etiology for CHF;
History of diabetes;
Outpatient use of inotropes within 6 months; or
Nesiritide within 6 months.
Patients with ≥ 4 positive criteria were considered high risk. All patients had weekly outpatient visits for 12 weeks and nesiritide patients received a 4- to 6-hr infusion at each weekly visit. Patients were observed for an additional period of 4 weeks after completion of the 3-month treatment period.
No significant difference was seen between treatment groups with regard to the frequency of serious adverse events (SAEs), and no adverse event (eg, heart failure, hypotension, renal AEs) occurred more frequently in the nesiritide groups. Out of a total of 1645 nesiritide infusions administered, only 11 (1%) were discontinued due to an AE.
Through 12 weeks, more patients in the standard-treatment group died or were hospitalized than in the nesiritide-treated groups (58% vs 48%, P = .185). Ten percent of standard-care patients died compared with 6% of nesiritide patients (P = .314), and 54% vs 46%, respectively, were hospitalized (P = .378) over the same period. Patients classified as high risk and treated with nesiritide showed statistically significant reductions in death and all-cause hospitalization compared with high-risk patients on standard care (52% vs 78%, P < .038). The same group also had higher survival rates and were out of hospital longer (mean 75.0 days vs 67.2 days, P = .027). Among the high-risk patients, 5% of nesiritide patients died over the course of the 12-week treatment period compared with 17% of high-risk patients on standard care.
A larger study is planned to assess the efficacy of serial outpatient infusions of nesiritide for several months in reducing death and hospitalizations in patients with chronic CHF who are at high risk for hospitalization.
Reference
Yancy CW, Saltzberg M, Berkowitz RL, for the FUSION Investigators. Management of patients with congestive heart failure after hospitalization: Results from the Follow Up Serial Infusions of Nesiritide (FUSION) trial. J Card Fail. 2003;9(5 suppl):S11. Abstract 034.