Nesiritide (Natrecor): a new treatment for acutely decompensated congestive heart failure

The care of the patient experiencing acutely decompensated congestive heart failure requires therapies that promote vasodilation and increase cardiac output while decreasing symptomatic hypotension and dysrhythmias. Nesiritide (Natrecor) is a new type of drug, recombinant human B-type natriuretic peptide (hBNP), approved for use in acutely decompensated congestive heart failure. The neurohormonal effects of endogenous BNP are reproduced by nesiritide. Indications, dosing, administration, and review of clinical trials are presented in this article.     

Nesiritide for the treatment of decompensated heart failure

Heart failure is the leading cause of hospitalizations in the USA, and is associated with significant morbidity, mortality and resource utilization. Established therapies for chronic heart failure have been shown to improve outcomes, but treatment for decompensated heart failure remains largely empiric. Nesiritide (Natrecor^®) is a synthetic analog of human B-type natriuretic peptide, a peptide released by the ventricular myocardium in response to increased wall tension. The physiologic effects of human B-type natriuretic peptide include natriuresis, vasodilation and neurohormonal modulation. In clinical trials, nesiritide has been shown to decrease cardiac filling pressures, increase cardiac index, and improve the clinical status of patients with acute decompensated heart failure. Compared with other available intravenous agents for heart failure, nesiritide is effective, generally well-tolerated with few adverse effects, and does not require invasive monitoring during administration. Nesiritide has proven to be an effective new treatment for patients with decompensated heart failure.     

Nesiritide for the treatment of decompensated heart failure

Heart failure is the leading cause of hospitalizations in the USA, and is associated with significant morbidity, mortality and resource utilization. Established therapies for chronic heart failure have been shown to improve outcomes, but treatment for decompensated heart failure remains largely empiric. Nesiritide (Natrecor) is a synthetic analog of human B-type natriuretic peptide, a peptide released by the ventricular myocardium in response to increased wall tension. The physiologic effects of human B-type natriuretic peptide include natriuresis, vasodilation and neurohormonal modulation. In clinical trials, nesiritide has been shown to decrease cardiac filling pressures, increase cardiac index, and improve the clinical status of patients with acute decompensated heart failure. Compared with other available intravenous agents for heart failure, nesiritide is effective, generally well-tolerated with few adverse effects, and does not require invasive monitoring during administration. Nesiritide has proven to be an effective new treatment for patients with decompensated heart failure.     

Nesiritide: a new drug for the treatment of decompensated heart failure

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.     

The ASCEND-HF trial: an acute study of clinical effectiveness of nesiritide and decompensated heart failure

Nesiritide has been approved by the US FDA for the treatment of acute decompensated heart failure since 2001. Subsequently, two meta-analyses questioned its impact on mortality and association with worsening renal function. Therefore, the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial was designed to assess the safety and efficacy of nesiritide in acute decompensated heart failure based on clinically relevant outcomes. In this article, the important findings and lessons learned from this landmark study are reviewed and potential evolving roles for nesiritide and natriuretic peptides in the future of heart failure therapy are proposed.     

How to use nesiritide in treating decompensated heart failure

Nesiritide (Natrecor), a synthetic formulation of B-type natriuretic peptide (BNP), is the first new parenteral agent to be approved for treating heart failure in more than a decade. In patients hospitalized with decompensated congestive heart failure, nesiritide promptly reduces pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and systemic vascular resistance, resulting in clinical improvement.     

Nesiritide: trials and tribulations

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.     

Natriuretic peptides for the treatment of acute heart failure: a focus on nesiritide in recent clinical trials

Nesiritide, a recombinant form of B-type natriuretic peptide, is a vasodilator and currently recommended as an additive therapy for patients with acute decompensated heart failure (ADHF) who have been optimized on loop diuretics. With hospitalizations for ADHF rising, appropriate selection of therapy becomes even more important to optimize efficacy and reduce adverse events. Nesiritide has many properties that antagonize the pathophysiologic processes of heart failure and has demonstrated a comparative benefit in previous reports; however, controversy still remains with respect to its efficacy and safety. Based on results from recent clinical trials, nesiritide has been shown to be safe at currently approved doses and strongly considered for the treatment of ADHF in patients who remain symptomatic despite optimal doses of intravenous loop divertics.     

Nesiritide utilization evaluation in a university teaching hospital

BACKGROUND AND OBJECTIVES: Nesiritide is a new vasodilator approved for decompensated heart failure (DHF). Compared with nitroglycerin, nesiritide improves haemodynamics and symptoms in the first 3 h of therapy. However, nesiritide is more expensive than nitroglycerin (US$380-1500 daily vs. US$2-5 daily). Since its approval in the US in late 2001, nesiritide use has increased dramatically in our institution. Nesiritide has become a focus of our multidisciplinary drug utilization initiative, aimed at performing a nesiritide utilization evaluation (NUE) and developing a nesiritide usage guideline. METHODS: Medical records of patients who received nesiritide from 1 October 2003 to 31 March 2004 were reviewed. Nesiritide utilization pattern was presented to the initiative group for guideline development. RESULTS: A total of 162 records were reviewed. A 22.6% of inappropriate usage was reported. The most significant inappropriate usage was in patients who received the agent for precardiac valvular surgery optimization, followed by those for diuresis in non-cardiac-related fluid overload states. The median duration of nesiritide therapy was 6 days (range 1-94). The median length of stay (LOS) in our institution was 14 days (National statistics DHF LOS: 5.3 days). Eliminating inappropriate nesiritide usage can lead to a potential of US$141 886 savings per year. CONCLUSION: Based on the results, a 48-h nesiritide restriction policy was implemented. Usage beyond 48 h requires Heart Failure Service approval. Future NUE will evaluate the effectiveness of this policy. The overall management of DHF also needs to be evaluated to improve efficiency of care.     

Nesiritide treatment of noncardiogenic pulmonary edema

OBJECTIVE: To report the efficacy of nesiritide in treating noncardiogenic pulmonary edema. CASE SUMMARY: A 50-year-old African American woman with a complex medical history including morbid obesity, acute bronchitis, obstructive sleep apnea, hypertension, and numerous hospitalizations for volume overload presented to the emergency department with severe dyspnea. A portable chest X-ray displayed perihilar congestion and bilateral pulmonary edema. An echocardiogram demonstrated normal left-ventricular systolic and diastolic function. She was aggressively treated with nitrates, diuretics, bronchodilators, and oxygen. Despite these efforts, the patient's arterial blood gas (ABG) continued to show respiratory acidosis, the oxygen saturation was significantly depressed, and the dyspnea continued. Since standard therapies were failing after 12 hours, the patient was treated with intravenous nesiritide. The results were profound in terms of rapid symptomatic and prognostic improvement (i.e., ABG) beginning within 45 minutes of administration, and the patient was discharged after a 5-day hospital course. DISCUSSION: Nesiritide is a human B-type natriuretic peptide that has been shown to improve hemodynamic function and symptoms associated with decompensated heart failure. This is primarily due to the actions of this medication, including diuresis, decreased mean arterial pressure, and improvement of pulmonary arterial occlusion pressure as determined by published clinical trial outcomes. This case describes the use of nesiritide as an effective adjunctive therapy in treating a patient with noncardiogenic pulmonary edema. CONCLUSIONS: Nesiritide appears to be an efficacious treatment for acute pulmonary edema, resistant to standard-of-care therapies, in the presence of normal left-ventricular function.     

Perioperative effects and safety of nesiritide following cardiac surgery in children

Nesiritide (Natrecor, Scios Inc), human B-type natriuretic peptide, has hemodynamic effects that may be beneficial in pediatric patients after cardiac surgery. Experience with nesiritide and pediatrics is limited. The purpose of this study was to evaluate perioperative effects and safety of nesiritide in pediatric cardiothoracic surgery. Seventeen patients with congenital heart disease undergoing cardiac surgery were given a loading dose (1 microg/kg) while on cardiopulmonary bypass (constant flow) followed by continuous infusion for 24 hours (0.01 microg/kg/min x 6 hours, then 0.02 microg/kg/min x 18 hours). A 7% decrease in mean blood pressure was seen following nesiritide loading dose on cardiopulmonary bypass. No patient required intervention for hypotension while receiving nesiritide load or infusion. Nesiritide load during surgery and continuous infusion after cardiac surgery in pediatric patients resulted in no significant hemodynamic compromise.     

Guidelines for acute decompensated heart failure treatment

OBJECTIVE: To describe the development of guidelines for the treatment of acute decompensated heart failure (ADHF) in the emergency department/observation unit (ED-OU) setting for hospitals that are part of a group purchasing organization (GPO). DATA SOURCES: A MEDLINE search (1966-March 2003) using the following search terms: cardiotonic agents; diuretic; dobutamine; heart failure, congestive; milrinone; natriuretic peptide, brain; nesiritide; nitroglycerin; vasodilator agents, was conducted. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in the English language were identified. All randomized studies and meta-analyses for each category of drugs were included. DATA SYNTHESIS: A group consensus method was used to develop guidelines. An expert panel reviewed and revised the guidelines. The final guidelines were approved June 1, 2003, and are described here. They are organized based upon a patient's symptomatology at the time the diagnosis of ADHF is made. Patients with evidence of volume overload require intravenous diuretics and/or intravenous vasodilators to alleviate the symptoms of ADHF. Patients with signs and symptoms of low cardiac output require inotropic support to manage their ADHF. A timeline for diagnosis, treatment, reassessment, and disposition is provided and encourages an early, aggressive approach to treating patients with ADHF. CONCLUSIONS: Hospitalization for ADHF is common and costly. Consensus guidelines for the treatment of ADHF did not previously exist, resulting in inconsistent and inefficient treatment. Consequently, hospitals struggling with the treatment of ADHF may find these guidelines and the process by which they were developed useful.     

The role of b-type natriuretic peptide in heart failure management

Heart failure is a complex clinical syndrome that manifests itself with signs and symptoms which are neither sensitive nor specific for the diagnosis of heart failure. Natriuretic peptides and in particular b-type natriuretic peptide (and nt-proBNP) are widely used in clinical practice around the world as a maker of heart failure. BNP is primarily released from the left ventricle in response to pressure and volume overload. The strongest evidence for the use of BNP is to rule in or rule out heart failure as cause of breathlessness in people who present to the emergency room. There is enthusiasm for use of BNP as a marker of heart failure severity as well as a predictor of outcomes in people with heart failure and trials are ongoing. Nesiritide, a recombinant form of BNP is currently being tested as a possible treatment in people with acutely decompensated heart failure.     

New advances and novel treatments in heart failure

As briefly summarized in this report, the prevalence of heart failure is high and it will continue to rise as the population ages. There will be over 1 million hospitalizations for acutely decompensated heart failure this year. The goals of treatment for patients with acutely decompensated heart failure are to lower cardiac filling pressures, remove fluids and improve symptoms of dyspnea, decrease vascular resistance, and increase cardiac output without activating the RAAS. There are few guidelines for the treatment of individuals with acutely decompensated heart failure and many different agents have been used in patients with this disease. Many of these drugs are not completely effective and may lead to serious adverse events. BNP is a natural protein produced by myocardial cells in response to ventricular distension, and its level is dramatically increased in patients with heart failure. The results of several recent clinical trials have shown that administration of nesiritide is safe and highly effective for the initial treatment of patients with acutely decompensated heart failure and can help physicians and nurses meet treatment goals for the management of patients with this serious condition.     

The use of recombinant human B-type natriuretic peptide (nesiritide) in the management of acute decompensated heart failure

Nesiritide is a synthetic human B-type natriuretic factor that has a balanced arterial and venous dilator effect, with natriuretic, diuretic, anti-aldosterone and antisympathetic action. It was launched in the US for the treatment of acute decompensated heart failure (ADHF) in August 2001 and, recently, in Switzerland and Israel. It has been demonstrated to provide more rapid and sustained haemodynamic stabilisation than glyceryl trinitrate and significant symptomatic improvement vs. placebo at 3 h, and to be safer than dobutamine. The main side effects associated with nesiritide therapy are asymptomatic and symptomatic hypotension, which are treated with dose reduction. When compared to dobutamine, the increased acquisition costs of nesiritide are completely offset by reduced intensity of hospital admissions and reduced readmission rate at 3 weeks.     

Nesiritide added to standard care favorably reduces systolic blood pressure compared with standard care alone in patients with acute decompensated heart failure

The Prospective Randomized Outcomes study of Acutely decompensated Congestive heart failure Treated Initially as Outpatients with Nesiritide (PROACTION) trial evaluated the safety of nesiritide administration in the emergency department in patients with decompensated heart failure. Patients (N=237) were treated for at least 12 hours with standard care plus either intravenous nesiritide or placebo. Compared to placebo, nesiritide favorably decreased systolic blood pressure (SBP) in patients with elevated baseline SBP, without negatively impacting patients with lower baseline SBP (SBP, >140 mm Hg: nesiritide, -28.7 mm Hg, vs placebo, -8.4 mm Hg [P<.001]; SBP, 101-140 mm Hg: nesiritide, -12.3 mm Hg, vs placebo, -5 mm Hg [P<.017]; SBP, <101 mm Hg: nesiritide, -1.2 mm Hg vs placebo, +16.7 mm Hg [P<.03]). Both treatment groups had similar incidences of symptomatic and asymptomatic hypotension. These data demonstrate that early administration of nesiritide in the emergency department is a safe and effective treatment of heart failure.     

Natriuretic peptide system: physiology and clinical utility

PURPOSE OF REVIEW: This review discusses the physiology of natriuretic peptides as a group and brain natriuretic peptide (BNP) in more detail. It will also highlight implications for the use of the natriuretic peptides in the diagnosis and treatment of patients with cardiovascular disease. RECENT FINDINGS: The heart secretes two major natriuretic peptides: atrial natriuretic peptide (ANP), which is synthesized in the atrial myocardium, and BNP, which is synthesized in the ventricular myocardium. Both ANP and BNP are released in response to atrial and ventricular stretch, respectively, and will cause balanced vasodilation, natriuresis, and inhibition of the sympathetic nervous system and the renin-angiotensin-aldosterone axis. BNP is reported to be the biochemical marker of choice for evaluating the acute risk of patients with cardiovascular disease states ranging from heart failure to myocardial ischemia. Increased blood BNP concentrations are highly predictive of the short- and long-term risk of cardiac death across the entire spectrum of acute coronary syndromes and in patients with decompensated congestive heart failure. Synthetic recombinant human BNP, which mimics the actions of endogenous BNP, has emerged as an important new therapeutic agent in patients with acute heart failure. SUMMARY: Current data suggest that single and serial plasma measurement of BNP concentrations is a useful tool in the diagnosis and risk stratification of patients with heart disease. Nesiritide, the human recombinant form of BNP, is a new promising parenteral treatment in decompensated heart failure.     

Preliminary experience with nesiritide in the pediatric population

Nesiritide is a recombinant formulation of brain-type natriuretic factor. Preliminary experience in the adult population suggests that nesiritide may be an effective agent in the treatment of decompensated congestive heart failure. Given its physiologic effects, it may be an effective agent in the pediatric population; however, to date, there are no reports regarding its use in infants and children. The authors retrospectively review their experience with nesiritide in 5 pediatric patients. The cohort of 5 patients included a diverse population with 2 patients who were status postcardiothoracic surgery, 2 with adult respiratory distress syndrome, and 1 in the recovery phase from septic shock. Although no direct measurement of cardiac output was feasible as none of the patients had a pulmonary artery catheter, other indicators of increased cardiac output were noted. These included improved peripheral perfusion with warming of the extremities and improvement of peripheral pulses in all of the patients, increased venous saturation in 2 of the patients, and maintenance of or increased urine output despite weaning or discontinuation of diuretics. In 3 of the patients, nesiritide was started as the primary agent to provide a decrease in systemic vascular resistance and augment cardiac output, while in the other 2 patients, nesiritide was used when other vasoactive agents failed to provide the desired effect or resulted in adverse effects.     

Using BNP to diagnose,manage, and treat heart failure

A rapid assay for B-type natriuretic peptide (BNP) not only can be used to diagnose heart failure, it can help the clinician evaluate effectiveness of therapy, determine when discharge from the hospital is appropriate, and estimate prognosis. A synthetic formulation of BNP (nesiritide) is used to treat decompensated heart failure, resulting in improved hemodynamics and symptoms.     

Critical review and recommendations for nesiritide use in the emergency department

Heart failure is a disease of epidemic proportions. Almost five million Americans suffer from heart failure and over 400,000 patients are newly diagnosed with heart failure each year. Indeed, heart failure is now the only cardiovascular disease that is increasing in incidence and prevalence. Costs related to heart failure are $18.8 billion per year and are steadily increasing. Although the outpatient management of these patients has seen substantial improvement in the last two decades, emergency department (ED) treatment of acute decompensated heart failure has remained largely unchanged since the late 1970s. Current ED therapy consists of diuretics, intravenous vasodilatators, and inotropes. Recently, the outcomes of several high-profile clinical trials evaluating intravenous nesiritide (human B-type natriuretic peptide) have suggested a benefit in select hospitalized patients. Such a therapy has potential to provide a therapeutic addition or alternative for emergency heart failure management. We discuss these trials' results, suggest their relationship to the ED population, and provide recommendations for appropriate ED use.