Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review outlines the chemical properties, pharmacology and clinical trials data which support the development of nesiritide (synthetic human B-type natriuretic peptide, or hBNP) as a therapeutic agent for patients with decompensated congestive heart failure. Nesiritide is a 32-amino acid peptide, structurally identical to endogenous hBNP. Clinical trials with single bolus, repeated boluses and sustained infusions of nesiritide have demonstrated prompt, significant and sustained reductions in pulmonary capillary wedge pressure and increases in cardiac output, consistent with a direct vasodilator effect. Nesiritide has a short half-life, approximately 18 min, which is not dependent upon renal function. It not associated with tachyphylaxis through 24 h of therapy. Nesiritide is not an inotrope, and its action is not dependent upon beta adrenergic receptors. The safety profile has been excellent; the major adverse effect is hypotension. The frequency of ventricular arrhythmia is not increased in patients treated with nesiritide. In our opinion, nesiritide has many attributes of an ideal first-line therapeutic agent for decompensated heart failure.
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PMID:Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure. 1599 6

Despite recent advances in the treatment of patients with acute decompensated heart failure, the cost of treatment for such patients remains considerable. IV diuretics, vasodilators, and positive inotropic agents are commonly prescribed. A retrospective data analysis was conducted to determine the cost effectiveness of nesiritide compared with milrinone and dobutamine administered in a hospital setting during episodes of acute decompensated heart failure. Nesiritide-treated patients demonstrated a significantly lower overall hospital length of stay, intensive care unit length of stay, and average cost per case compared with dobutamine or milrinone. Although the acquisition cost of nesiritide was higher than that of milrinone and dobutamine, nesiritide was a more cost-effective treatment option for patients with acute decompensated heart failure in this study.
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PMID:Increased cost effectiveness with nesiritide vs. milrinone or dobutamine in the treatment of acute decompensated heart failure. 1633 Sep 6

B-type natriuretic peptide (BNP) is an endogenous cardiac neurohormone, produced in the ventricles in response to pressure and volume elevation. Nesiritide is identical to endogenous BNP and is synthesized using recombinant DNA technology. It is currently used in the treatment of acute decompensated heart failure. In clinical trials, nesiritide has been shown to decrease pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance, as well as increase cardiac index and stroke volume index. Infusions of nesiritide have led to increased diuresis and natriuresis. Patients treated with nesiritide have reported improvements in global clinical status, dyspnea, and fatigue. Therapy with nesiritide has resulted in decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels, as well as reduced ventricular ectopy and ventricular tachycardia. Heart rate variability also improved with nesiritide. Patients with acute coronary syndromes, serious arrhythmia, renal disease, diastolic dysfunction, or vasopressor dependence have been safely managed with nesiritide. Early treatment with nesiritide in the emergency department may lead to decreased length of hospital stay and reduced readmission rates compared to standard care. Outpatient serial infusions of nesiritide in severe heart failure patients on optimal medical therapy may result in improved clinical status, increased ejection fraction, reduced aldosterone and endothelin-1 levels, and decreased hospitalizations. Potential future uses of nesiritide include treatment of acute coronary syndromes, pulmonary hypertension, bronchospasm in chronic lung disease, and as antifibrotic/anti-remodeling therapy or bridge to cardiac transplant. The possibility of subcutaneous injections of nesiritide has been studied in both animals and humans.
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PMID:Nesiritide: past, present, and future. 1633 35

Nesiritide (recombinant B-type natriuretic peptide) is often given for symptomatic relief of acute decompensated heart failure in adults. The literature describing the safety or efficacy of nesiritide in children is minimal, and we know of no data that describe the effects of a nesiritide overdose in adults or children. A 3-year-old, 10.9-kg girl was admitted to the pediatric intensive care unit with the diagnosis of dilated cardiomyopathy and acute decompensated heart failure. She received several vasoactive infusions during her admission, including nesiritide. On hospital day 47 (day 45 of nesiritide therapy), the patient received an 18-fold overdose of nesiritide, with no hemodynamic, cardiac, or renal sequelae. She subsequently underwent successful cardiac transplantation. The nesiritide treatment duration was longer for this patient than the 45 days previously reported in a pediatric patient. No hemodynamic instability or cardiac or renal sequelae were associated with the large, inadvertent bolus in our patient. This case report demonstrates the lack of adverse events in a pediatric patient administered nesiritide beyond the recommended dosing parameters. Increased vigilance is always advised when administering drugs not commonly given to pediatric patients.
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PMID:Administration of a large nesiritide bolus dose in a pediatric patient: case report and review of nesiritide use in pediatrics. 1646 33

A term (39-wk-old) male neonate exhibited respiratory distress and anuria within 2 days of birth. The patient was diagnosed with pulmonary hypertension, polycystic kidney disease, and heart failure; his initial B-type natriuretic peptide concentration was 2460 pg/ml. After minimal response to loop diuretics, the patient was given an infusion of nesiritide 0.01 microg/kg/minute, with no loading dose. Urine output increased over 400%, and cardiac function improved. Nesiritide was titrated to 0.03 microg/kg/minute with no hypotension, decreased renal function, or adverse cardiac sequelae over the next 6 days. No subsequent changes in cardiac function occurred during the infant's stay in a progressive care unit, but he died at age 5.5 months due to sepsis. This case report demonstrates the successful first use of nesiritide therapy in a neonate with renal disease. Further studies are warranted to evaluate the safety and administration of this agent in the neonatal patient population.
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PMID:Nesiritide therapy in a term neonate with renal disease. 1646 34

This retrospective substudy of the Follow-Up Serial Infusions of Nesiritide trial (FUSION I) assessed the feasibility of outpatient administration of nesiritide in 138 patients with co-morbid advanced heart failure and renal insufficiency (estimated creatinine clearance<60 ml/min). Patients received 1 of 3 treatments once weekly for 12 weeks: standard care (SC), SC plus nesiritide 0.005 microg/kg/min, or SC plus nesiritide 0.010 microg/kg/min. The addition of nesiritide to SC was well tolerated, with no evidence of worsening renal function, compared with SC only and was associated with a reduction in the rate of all-cause hospitalization or mortality through week 12, with hazard ratios of 2.027 (95% confidence interval 1.165 to 3.525) and 2.219 (95% confidence interval 1.233 to 3.992) for the SC-only group compared with the SC plus 0.005 microg/kg/min and SC plus 0.010 microg/kg/min nesiritide groups, respectively. These findings raise the hypothesis that adjunctive therapy with nesiritide on an outpatient basis may be beneficial for patients with advanced heart failure and renal insufficiency. Further study is warranted to test the validity of this finding.
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PMID:Potential applications of outpatient nesiritide infusions in patients with advanced heart failure and concomitant renal insufficiency (from the Follow-Up Serial Infusions of Nesiritide [FUSION I] trial). 1682 98

This study sought to determine the potential of recombinant B-type natriuretic peptide (nesiritide) for the treatment of pediatric decompensated heart failure. Nesiritide is a widely used and effective treatment for decompensated heart failure (HF) in adults, but its safety and efficacy in pediatric patients is unclear. Outcomes of 55 separate nesiritide infusions of varying durations in 32 patients (13 males and 19 females; mean age, 8.01 years; range, 0.01-20.4) were evaluated prospectively. All patients received nesiritide in the intensive care unit. The starting dose (0.01 microg/kg/min) was titrated to a maximum of 0.03 microg/kg/min. All patients were monitored for clinical signs and symptoms, hemodynamics, urine output, electrolytes, oxygen requirements, and oral intake. Functional status was assessed by patients and/or their parents. All patients successfully underwent initiation and titration of nesiritide infusion. No hypotension or arrhythmias were noted during 478 cumulative days of therapy. Nesiritide was given safely with vasoactive medications. Mean urine output improved from 2.35 +/- 1.71 cc/kg/hr on the day before nesiritide initiation (baseline) to 3.10 +/- 1.94 cc/kg/hr on day 4 of treatment (p < 0.01). Serum creatinine decreased from 1.04 to 0.92 mg/dl (p = 0.096), mean central venous pressure from 13 to 7 mmHg (p = 0.018), and mean weight from 30.4 to 29.7 kg (p < 0.001) with therapy. Thirst, as subjectively assessed by patients old enough to respond, decreased with infusion in 31 of 42 cases (74%). Mean New York Heart Association functional class improved significantly (p < 0.001). Nesiritide infusion, alone or in combination, is a safe treatment for decompensated HF in pediatric patients. It is associated with decreased thirst and improved urine output and functional status, and it may be efficacious in the treatment of pediatric HF.
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PMID:A prospective evaluation of nesiritide in the treatment of pediatric heart failure. 1683 89

Nesiritide is the recombinant form of human B-type (brain) natriuretic peptide (BNP), and its amino acid sequence is identical to that of endogenous human BNP. Administration of nesiritide results in venous and arterial vasodilation, as well as enhanced diuresis. Given the many limitations of therapies previously available for the treatment of acute decompensated heart failure, the anticipation was that nesiritide would offer a safer and more effective therapeutic option. Recently, two meta-analyses raised the question of safety with nesiritide therapy, specifically an increased risk of renal dysfunction and mortality. Although several studies generated information regarding the potential role of nesiritide in various settings, the questions raised by the meta-analyses are concerning. Our hope is that future clinical trials will address the concerns raised and provide a better understanding of the role of nesiritide in the management of acute decompensated heart failure. Until these data are available, nesiritide use should be limited.
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PMID:Nesiritide: harmful or harmless? 1699 57

Standard therapy for acute decompensated heart failure, a major health problem, consists of intravenous diuretics, vasodilators, and positive inotropic agents. Nesiritide, a recombinant form of human B-type natriuretic peptide, is the only drug specifically approved for this indication. Recent meta-analyses have reported an increased risk of worsening renal function and 30-day mortality with nesiritide administration. These data understandably require physicians to carefully reevaluate their current use of nesiritide in patients with acute decompensated heart failure. In performing this reevaluation, it is important to consider our understanding of the underlying disease state, the limitations and results of these meta-analyses, and new data that provide additional insight into the possible risks and benefits associated with nesiritide therapy. Until additional therapeutic trials are conducted, therapeutic choices must be based on symptomatic and hemodynamic improvement and limited, imperfect available data, which may continue to support the use of nesiritide for its established indication.
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PMID:Nesiritide: trials and tribulations. 1705 28

The treatment of acute decompensated heart failure (ADHF) remains a therapeutic challenge. Nesiritide was approved by the FDA in 2001 for the treatment of patients with ADHF who have dyspnea at rest or with minimal exertion. Although widely adopted for the treatment of ADHF due to its ability to decrease ventricular filling pressures and to provide mild symptomatic benefit, recent analyses have suggested that nesiritide worsens renal function and increases mortality. Although some discount these analyses that demonstrate the potential dangers of nesiritide, others have stated that its use at the present time must be weighed against the possibility of worse outcomes. A large outcomes trial in patients with ADHF would help clarify the role of nesiritide.
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PMID:Nesiritide: a reappraisal of efficacy and safety. 1726 70


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