Effect of nesiritide versus dobutamine on short-term outcomes in the treatment of patients with acutely decompensated heart failure.

OBJECTIVES: This study was designed to determine whether nesiritide, administered for acute decompensated congestive heart failure (CHF), affects healthcare costs by hospital length of stay (LOS), readmissions and short-term mortality, compared to dobutamine. BACKGROUND: Dobutamine is a commonly used inotropic treatment for CHF. Although dobutamine may have favorable hemodynamic and symptomatic effects, its use may be associated with side effects such as tachycardia, cardiac arrhythmias and myocardial ischemia. Nesiritide (B-type natriuretic peptide) is a new intravenous (IV) drug that produces hemodynamic and symptomatic improvement through balanced vasodilatory effects, neurohormonal suppression and enhanced natriuresis and diuresis. METHODS: From an open-label randomized study of nesiritide versus standard care (SC) in patients with CHF requiring hospitalization, we compared short-term outcome data from patients given nesiritide (0.015 or 0.03 microg/kg per min) with a subgroup of SC patients given dobutamine. A total of 261 patients are included in this analysis. RESULTS: Compared to dobutamine, both nesiritide doses were administered for a shorter total duration (p < 0.001), and the total duration of all IV vasoactive therapy (including study drug) was also shorter (p less-than-or-equal 0.012). Although there was no difference in LOS, there was a trend toward decreased readmissions in the two nesiritide groups (8% and 11%, respectively, vs. 20% in the dobutamine group). Six-month mortality was lower in the nesiritide groups. CONCLUSIONS: Treatment of decompensated CHF with nesiritide may lead to lower healthcare costs and reduced mortality compared to treatment with dobutamine.

Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE).

BACKGROUND: The ADHERE is designed to study characteristics, management, and outcomes in a broad sample of patients hospitalized with acute decompensated heart failure. Heart failure is a leading cause of hospitalization for adults older than 65 years in the United States. Most available data on these patients are limited by patient selection criteria and study design of clinical trials and single-center studies. METHODS: Participating hospitals identify patients with a primary or secondary discharge diagnosis of heart failure. Medical history, management, treatments, and health outcomes data are collected through review of medical records and entered into a database via secure web browser technology. RESULTS: As of January 2004, data on 107 362 patients have been received from 282 participating hospitals. Of enrollees with available analyzable data (N = 105 388 from 274 hospitals), the mean age was 72.4 (+/-14.0), and 52% were women. The most common comorbid conditions were hypertension (73%), coronary artery disease (57%), and diabetes (44%). Evidence of mild or no impairment of systolic function was found in 46% of patients. Inhospital mortality was 4.0% and the median hospital length of stay was 4.3 days. CONCLUSIONS: The ADHERE demonstrates both the feasibility and significant implications of gathering representative data on large numbers of patients hospitalized with heart failure. Initial data provided important insights into the clinical characteristics and patterns of care of these patients. Ongoing registry work will provide the framework for improved treatment strategies for patients hospitalized with decompensated heart failure.

Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study.

BACKGROUND: Dobutamine is commonly used as a means of treating decompensated congestive heart failure (CHF). Although typically effective at improving short-term hemodynamics and symptomatology, the frequent occurrence of arrhythmias and tachycardia is undesirable. In this randomized, multicenter trial, we compared the safety and clinical effectiveness of the cardiac hormone nesiritide (human B-type natriuretic peptide) with dobutamine in hospitalized patients with decompensated CHF. METHODS: The study population consisted of 255 patients who were randomized to 1 of 2 doses of intravenous nesiritide (0.015 or 0.03 microg/kg/min) or dobutamine (> or =5 microg/kg/min) and stratified by means of an earlier history of ventricular tachycardia. Patients were also assessed with 24 hour Holter recordings immediately before and during study drug therapy and by means of signs and symptoms of CHF. RESULTS: Dobutamine significantly increased the mean (1) number of ventricular tachycardia events per 24 hours by 48 +/- 205 (P =.001), (2) repetitive ventricular beats per hour by 15 +/- 53 (P =.001), (3) premature ventricular beats per hour by 69 +/- 214 (P =.006), and (4) heart rate by 5.1 +/- 7.7 beats per minute (P <.001). These end points were significantly decreased or unchanged in the nesiritide groups. Nesiritide did not increase heart rate, despite a greater reduction of blood pressure. Both drugs were similarly effective means of improving signs and symptoms of CHF. CONCLUSIONS: Dobutamine is associated with substantial proarrhythmic and chronotropic effects in patients with decompensated CHF, whereas nesiritide actually reduces ventricular ectopy or has a neutral effect. Compared with dobutamine, nesiritide may be a safer, short-term treatment for patients with decompensated CHF.

Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I trial).

The Follow-Up Serial Infusions of Nesiritide pilot study was designed to assess the safety and tolerability of outpatient serial infusions of nesiritide in 210 patients with decompensated heart failure who were randomly assigned to usual care only or usual care plus weekly infusions of nesiritide at dosages of 0.005 or 0.01 microg/kg/min for 12 weeks. The mean age +/- SD of the entire population was 67 +/- 13 years; 70% were men, and 80% were white. Mean baseline serum creatinine levels were 1.8 +/- 0.7 mg/dl, and mean left ventricular ejection fraction was 0.28 +/- 0.15%. Diabetes mellitus was present in 106 patients (50%), and atrial arrhythmias were present in 100 patients (48%). A totalof 1,645 nesiritide infusions was administered; 11 (< 1%) were discontinued due to an adverse event. All treatment groups had a similar frequency of adverse events and experienced improvements in quality of life. Administration of nesiritide resulted in acute decreases in aldosterone and endothelin-1 concentrations. Although there were no statistically significant differences among groups by outcome, prospectively defined higher risk subgroups demonstrated significant decreases in cardiovascular events. These results demonstrate the safety and feasibility of administering nesiritide in an outpatient setting. Additional studies are needed to determine the effect of outpatient serial infusions of nesiritide on rates of morbidity and mortality in advanced heart failure.

Subcutaneous administration of the cardiac hormone BNP in symptomatic human heart failure.

BACKGROUND: Brain natriuretic peptide (BNP) is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin-aldosterone-inhibiting and lusitropic properties. We have demonstrated that acute subcutaneous (SQ) administration of BNP in experimental congestive heart failure results in elevation of plasma BNP and its second messenger 3',5'-cyclic guanosine monophosphate (cGMP) with natriuresis and reduction in cardiac filling pressures. Furthermore, chronic subcutaneous BNP in experimental congestive heart failure also resulted in increases in cardiac output and decreases in pulmonary capillary wedge pressure and systemic vascular resistance. METHODS: The objective of the current study was to assess the safety and efficacy of repeated doses of subcutaneous human BNP, nesiritide, a recombinant form of human BNP (Scios Inc, Fremont, CA) in human subjects with New York Heart Association class II-III congestive heart failure. We defined the cardiorenal and humoral responses to subcutaneous BNP (nesiritide) administered every 12 hours with a total of 5 doses over 72 hours in a single-blind placebo-controlled design (n=8). The mean dose of nesiritide was 10 microg/kg every 12 hours. RESULTS: Initial saline placebo resulted in no change in any measured parameters (P<.05 versus baseline). With the first dose of BNP (nesiritide), cardiac output increased (4.8+/-0.4 to 6.4+/-0.5 L/min) and systolic blood pressure decreased (125+/-5 to 104+/-3 mm Hg) without a change in heart rate. Plasma BNP (167+/-115 to 830+/-470 pg/mL), cGMP (4+/-2 to 14+/-4 pmol/mL), and urinary cGMP excretion (3900+/-930 to 10,600+/-5000 pmol/min) increased with natriuresis and diuresis. Both plasma renin activity and plasma aldosterone decreased. These favorable biologic responses were observed with the fifth dose 72 hours after the initial dose. All the subjects tolerated the study well without any adverse events except for 1 subject who had a vasovagal episode during micturition after receiving the fifth dose on day 3. CONCLUSION: We conclude that subcutaneous administration of BNP (nesiritide) represents a novel and efficacious therapeutic strategy in human congestive heart failure to deliver BNP, a cardiac hormone which possesses unique cardiorenal and neurohumoral properties.