Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure.

BACKGROUND: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial prospectively compared the efficacy of an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided heart failure treatment strategy (target NT-proBNP level <1,000 pg/ml) with optimal medical therapy alone in high-risk patients with heart failure and reduced ejection fraction. When the study was stopped for futility, 894 patients had been enrolled. OBJECTIVES: The purpose of this study was to assess treatment-related quality-of-life (QOL) and economic outcomes in the GUIDE-IT trial. METHODS: The authors prospectively collected a battery of QOL instruments at baseline and 3, 6, 12, and 24 months post-randomization (collection rates 90% to 99% of those eligible). The principal pre-specified QOL measures were the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI). Cost data were collected for 735 (97%) U.S. RESULTS: Baseline variables were well balanced in the 446 patients randomized to the NT-proBNP-guided therapy and 448 to usual care. Both the KCCQ and the DASI improved over the first 6 months, but no evidence was found for a strategy-related difference (mean difference [biomarker-guided - usual care] at 24 months of follow-up 2.0 for DASI [95% confidence interval (CI): -1.3 to 5.3] and 1.1 for KCCQ [95% CI: -3.7 to 5.9]). Total winsorized costs averaged $5,919 higher in the biomarker-guided strategy (95% CI: -$1,795, +$13,602) over 15-month median follow-up. CONCLUSIONS: A strategy of NT-proBNP-guided HF therapy had higher total costs and was not more effective than usual care in improving QOL outcomes in patients with heart failure and a reduced ejection fraction. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

A cost effectiveness study establishing the impact and accuracy of implementing the NICE guidelines lowering plasma NTproBNP threshold in patients with clinically suspected heart failure at our institution.

AIMS: The 2014 National Institute of Clinical Excellence (NICE) guidelines on the management of acute heart failure recommended using a plasma NT-proBNP threshold of 300pg/ml to assist in ruling out the diagnosis of heart failure (HF), updating previous guidelines recommending using a threshold of 400pg/ml. NICE based their recommendations on 6 studies performed in other countries. This study sought to determine the diagnostic and economic implications of using these thresholds in a large unselected UK population. METHODS: Patient and clinical demographics were recorded for all consecutive suspected HF patients over 12months, as well as clinical outcomes including time to HF hospitalisation and time to death (follow up 15.8months). RESULTS: Of 1995 unselected patients admitted with clinically suspected HF, 1683 (84%) had a NTproBNP over the current NICE recommended threshold, of which 35% received a final diagnosis of HF. Lowering the threshold from 400 to 300pg/ml would have involved screening an additional 61 patients and only would have identified one new patient with HF (sensitivity 0.985, NPV 0.976, area under the curve (AUC) at 300pg/ml 0.67; sensitivity 0.983, NPV 0.977, AUC 0.65 at 400pg/ml). The economic implications of lowering the threshold would have involved additional costs of £42,842.04 (£702.33 per patient screened, or £ 42,824.04 per new HF patient). CONCLUSION: Applying the recent updated NICE guidelines to an unselected real world population increases the AUC but would have a significant economic impact and only identified one new patient with heart failure.

Medical resource use, costs, and quality of life in patients with acute decompensated heart failure: findings from ASCEND-HF.

BACKGROUND: The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) randomly assigned 7,141 participants to nesiritide or placebo. Dyspnea improvement was more often reported in the nesiritide group, but there were no differences in 30-day all-cause mortality or heart failure readmission rates. We compared medical resource use, costs, and health utilities between the treatment groups. METHODS AND RESULTS: There were no significant differences in inpatient days, procedures, and emergency department visits reported for the first 30 days or for readmissions to day 180. EQ-5D health utilities and visual analog scale ratings were similar at 24 hours, discharge, and 30 days. Billing data and regression models were used to generate inpatient costs. Mean length of stay from randomization to discharge was 8.5 days in the nesiritide group and 8.6 days in the placebo group (P = .33). Cumulative mean costs at 30 days were $16,922 (SD $16,191) for nesiritide and $16,063 (SD $15,572) for placebo (P = .03). At 180 days, cumulative costs were $25,590 (SD $30,344) for nesiritide and $25,339 (SD $29,613) for placebo (P = .58). CONCLUSIONS: The addition of nesiritide contributed to higher short-term costs and did not significantly influence medical resource use or health utilities compared with standard care alone.

Evaluación económica de la determinación del propéptido natriurético cerebral n-terminal (NT-proBNP) en pacientes con disnea en los servicios de urgencias españoles / Economic evaluation of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) test in Spanish emergency department patients with dyspnea

Introducción. Analizar la eficiencia de añadir la determinación NT-proBNP al examen clínico convencional (ECC) para el diagnóstico de insuficiencia cardiaca (IC) en pacientes con disnea que acuden a servicios de urgencias (SU) españoles. Material y métodos. Se desarrolló un árbol de decisión para evaluar los resultados clínicos y económicos de ambas alternativas durante 60 días de seguimiento desde la visita al SU en pacientes hospitalizados y no hospitalizados. Los parámetros clínicos fueron principalmente obtenidos del estudio PRIDE y validados por médicos de SU y cardiólogos. El punto de corte de la determinación NT-proBNP fue de 900pg/mL (sensibilidad del 90% y especificidad del 85%). En base a datos españoles publicados, se asumió que el 65% de pacientes con disnea sufrían IC. El uso de recursos fue identificado mediante opinión de expertos y evaluado desde la perspectiva del Sistema Nacional de Salud (SNS). El análisis comparó el diagnóstico final del paciente con el diagnóstico realizado en el SU. Se realizaron diversos análisis de sensibilidad para evaluar la incertidumbre del modelo. Resultados. El diagnóstico incorporando la determinación NT-proBNP fue correcto en el 91,96% de los pacientes (59,09% verdaderos positivos y 32,87% verdaderos negativos) frente al 85,53% mediante ECC (50,79% verdaderos positivos y 34,74% verdaderos negativos). La incorporación de la determinación NT-proBNP resultó tener un coste menor (3.720€ versus 5.188€). Los análisis de sensibilidad realizados confirmaron los resultados. Conclusiones. La incorporación de la determinación NT-proBNP en el diagnóstico del paciente con disnea en los SU españoles muestra un menor coste y un mayor porcentaje de pacientes correctamente diagnosticados comparado con el ECC desde la perspectiva del SNS (AU)

Introduction. To assess the efficiency of adding the NT-proBNP test to the standard clinical evaluation (SCE) for the diagnosis of heart failure (HF) in Spanish emergency department (ED) patients with dyspnea. Material and methods. A decision-tree was developed to evaluate the clinical and economic outcomes of the two diagnostic alternatives 60 days after ED admission in hospitalized and non-hospitalized patients. Clinical parameters were mainly extracted from the PRIDE study and were validated by expert ED physicians and cardiologists. The cut-off point for the NT-proBNP test was 900pg/mL (sensitivity of 90% and specificity of 85%). We assumed that 65% of patients with dyspnea had HF, based on published Spanish data. Resource use was obtained by expert opinion and evaluated from the public payer perspective (Spanish National Health Service (NHS)). The analysis compared the final diagnosis with the ED diagnosis. Multiple sensitivity analyses were carried out to evaluate the uncertainty of the model. Results. The diagnosis using NT-proBNP testing was correct in 91.96% of patients (59.09% true positive and 32.87% true negative) vs. 85.53% using SCE alone (50.79% true positive and 34.74% true negative). Costs were lower in patients receiving NT-proBNP testing (€3,720 versus €5,188). The sensitivity analyses confirmed the results. Conclusions. The use of the NT-proBNP test for the assessment and management of Spanish emergency department patients with dyspnea is less costly and shows a higher percentage of correctly-diagnosed patients from the Spanish NHS perspective than SCE alone (AU)

B-type natriuretic peptide in the evaluation and management of dyspnoea in primary care.

OBJECTIVES: The rapid and accurate diagnosis of heart failure in primary care is a major unmet clinical need. We evaluated the additional use of B-type natriuretic peptide (BNP) levels. DESIGN: A randomized controlled trial. SETTING: Twenty-nine primary care physicians in Switzerland and Germany coordinated by the University Hospital Basel, Switzerland. SUBJECTS: A total of 323 consecutive patients presenting with dyspnoea. INTERVENTIONS: Assignment in a 1 : 1 ratio to a diagnostic strategy including point-of-care measurement of BNP (n = 163) or standard assessment without BNP (n = 160). The total medical cost at 3 months was the primary end-point. Secondary end-points were diagnostic certainty, time to appropriate therapy, functional capacity, hospitalization and mortality. The final diagnosis was adjudicated by a physician blinded to the BNP levels. RESULTS: Heart failure was the final diagnosis in 34% of patients. The number of hospitalizations, functional status and total medical cost at 3 months [median $1655, interquartile range (IQR), 850-3331 vs. $1541, IQR 859-2827; P = 0.68] were similar in both groups. BNP increased diagnostic certainty as defined by the need for further diagnostic work-up (33% vs. 45%; P = 0.02) and accelerated the initiation of the appropriate treatment (13 days vs. 25 days; P = 0.01). The area under the receiver-operating characteristics curve for BNP to identify heart failure was 0.87 (95% confidence interval, 0.81-0.93). CONCLUSIONS: The use of BNP levels in primary care did not reduce total medical cost, but improved some of the secondary end-points including diagnostic certainty and time to initiation of appropriate treatment.

Does bnp testing aid diagnosis of heart failure?

Heart failure is common, causes major disability and often shortens life. Two UK guidelines advocate the measurement of plasma concentrations of B-type natriuretic peptide (BNP) in diagnosis of chronic heart failure, either in combination with, or as an alternative to, an ECG.1,2 Here we review the evidence for BNP testing in the diagnosis of chronic heart failure, and discuss the implications in terms of availability of the test.

Cost-effectiveness of B-type natriuretic peptide testing.

As with any other diagnostic method, the cost-effectiveness of B-type natriuretic peptide (BNP) testing depends on the indication of its use and the specific clinical setting. The use of BNP levels, in conjunction with other clinical information, provides information that seems to be particularly helpful in the diagnosis, prognosis, and management of heart failure (HF) as well as screening for left ventricular systolic dysfunction. In the screening for asymptomatic left ventricular systolic dysfunction, BNP testing seems to be cost-effective (<$50,000 per quality-adjusted life-years gained) when used in a population with a prevalence of at least 1%. BNP testing, in fact, results in cost savings in the diagnosis of HF. Although the data are less robust, BNP seems cost-effective in the risk stratification of hospitalized HF patients when compared with echocardiography. Because BNP guidance seems to reduce the number of rehospitalizations in recently hospitalized patients with chronic HF, the use of BNP is also most likely cost-effective in this indication. For the remaining and, in part, evolving indications, further studies are needed to assess cost-effectiveness.

Nesiritide in acute decompensated heart failure: current status and future perspectives.

Acute decompensated heart failure (ADHF) is a growing public health problem with high mortality and costs. ADHF often, if not usually, occurs in the setting of cardiovascular and noncardiovascular comorbidities as well as advanced age. New insights provide support for the concept of heart failure as a state of deficiency of and/or resistance to endogenous B-type natriuretic peptide. The primary goals of ADHF therapy are to relieve symptoms and optimize volume status with minimal side effects. Few therapies are proven to effectively do so. Nesiritide is a balanced vasodilator with favorable neurohumoral effects and is superior to placebo in providing rapid symptom relief and to nitroglycerin in reducing filling pressures. Recent trials confirm a lack of renal toxicity at recommended doses. An adequately powered multinational mortality trial is underway. Nesiritide represents a proven therapy for normotensive/hypertensive ADHF patients with severe symptoms at rest.

Outcomes of patients hospitalized for acute decompensated heart failure: does nesiritide make a difference?

BACKGROUND: Nesiritide is indicated in the treatment of acute decompensated heart failure. However, a recent meta-analysis reported that nesiritide may be associated with an increased risk of death. Our goal was to evaluate the impact of nesiritide treatment on four outcomes among adults hospitalized for congestive heart failure (CHF) during a three-year period. METHODS: CHF patients discharged between 1/1/2002 and 12/31/2004 from the Adventist Health System, a national, not-for-profit hospital system, were identified. 25,330 records were included in this retrospective study. Nesiritide odds ratios (OR) were adjusted for various factors including nine medications and/or an APR-DRG severity score. RESULTS: Initially, treatment with nesiritide was found to be associated with a 59% higher odds of hospital mortality (Unadjusted OR = 1.59, 95% confidence interval [CI]: 1.31-1.93). Adjusting for race, low economic status, APR-DRG severity of illness score, and the receipt of nine medications yielded a nonsignificant nesiritide OR of 1.07 for hospital death (95% CI: 0.85-1.35). Nesiritide was positively associated with the odds of prolonged length of stay (all adjusted ORs = 1.66) and elevated pharmacy cost (all adjusted ORs > 5). CONCLUSION: In this observational study, nesiritide therapy was associated with increased length of stay and pharmacy cost, but not hospital mortality. Randomized trials are urgently needed to better define the efficacy, if any, of nesiritide in the treatment of decompensated heart failure.

B-type natriuretic peptide testing is associated with reduced cost in patients with secondary diagnosis of heart failure.

BACKGROUND: This study was designed to examine the effect of BNP use on resource utilization and clinical outcome in hospitalized patients with heart failure (HF). METHODS: Details of all (1788) hospital discharges over 12 months with ICD-9 code 428.x diagnosis were matched to the laboratory and echocardiography databases. Multiple linear regression and logistic regression analysis were performed using use of BNP testing, number of secondary diagnoses, sex, age, financial status, cardiology care, performance of echocardiography as dependent variables to predict length of stay, payable amount and discharge status in separate HF as primary and HF as secondary diagnosis groups. RESULTS: Use of BNP measurement was associated with an average $ Singapore 1305 (p=0.007) decrease in payable amount in patients with secondary diagnosis of HF when controlled for other variables. Its use was associated with reduced use of echocardiography in both primary (odds ratio: 0.04) and secondary (OR: 0.08) diagnosis groups. CONCLUSIONS: Use of BNP measurement was associated with reduced cost of hospitalization in patients with a secondary diagnosis of HF and with reduced use of echocardiography in heart failure patients. This suggests the potential of BNP measurement to reduce costs for the many patients whose multiple problems include HF.

Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea.

BACKGROUND: B-type natriuretic peptide (BNP) is a quantitative marker of heart failure that seems to be helpful in its diagnosis. METHODS: We performed a prospective randomized study (B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation) including 452 patients who presented to the emergency department with acute dyspnea to estimate the long-term cost-effectiveness of BNP guidance. Participants were randomly assigned to a diagnostic strategy involving the measurement of BNP levels (n = 225) or assessment in a standard manner (n = 227). Nonparametric bootstrapping was used to estimate the distribution of incremental costs and effects on the cost-effectiveness plane during 180 days of follow-up. RESULTS: Testing of BNP induced several important changes in management of dyspnea, including a reduction in the initial hospital admission rate, the use of intensive care, and total days in the hospital at 180 days (median, 10 days [interquartile range, 2-24 days] in the BNP group vs 14 days [interquartile range, 6-27 days] in the control group; P = .005). At 180 days, all-cause mortality was 20% in the BNP group and 23% in the control group (P = .42). Total treatment cost was significantly reduced in the BNP group (7930 dollars vs 10,503 dollars in the control group; P = .004). Analysis of incremental 180-day cost-effectiveness showed that BNP guidance resulted in lower mortality and lower cost in 80.6%, in higher mortality and lower cost in 19.3%, and in higher or lower mortality and higher cost in less than 0.1% each. Results were robust to changes in most variables but sensitive to changes in rehospitalization with BNP guidance. CONCLUSION: Testing of BNP is cost-effective in patients with acute dyspnea.

Pharmacoeconomic modeling of nesiritide versus dobutamine for decompensated heart failure.

STUDY OBJECTIVE: To model the cost-effectiveness of nesiritide compared with dobutamine in patients with decompensated heart failure. DESIGN: Cost-effectiveness analysis. MEASUREMENTS AND MAIN RESULTS: A decision tree model was derived from randomized clinical trial data and data from a previously published economic study. Four cost-effectiveness analyses were performed: analysis 1 -- full probabilistic analysis, repeatedly sampled probabilities for 6-month mortality and hospital readmission from distributions based on 95% confidence intervals (CIs); analysis 2 -- best-case nesiritide analysis, used the limiting values of the 95% CI favorable to nesiritide; analysis 3 -- best-case dobutamine analysis, used the limiting values of the 95% CI favorable to dobutamine; and analysis 4 -- replicated the previously published cost-effectiveness study and served as a methodologic control. Fifty-one consecutive Monte Carlo simulations for cohorts of 1000 hypothetical patients were performed for each analysis. Incremental cost, incremental effectiveness, and incremental cost-effectiveness ratios (ICERs) were calculated for nesiritide versus dobutamine. Analysis 1 showed a mean ICER of 767 US dollars/life-year gained for nesiritide versus dobutamine (incremental cost 251 US dollars +/- 290 US dollars, incremental effectiveness 0.33 +/- 0.22 yr). The 95% confidence region surrounding this point estimate spanned all four quadrants of the incremental cost-effectiveness scatterplot, suggesting inconclusive results. Nesiritide was the dominant treatment strategy in analysis 2 (incremental cost -734 US dollars+/- 106 US dollars, incremental effectiveness 1.19 +/- 0.07 yrs), whereas dobutamine was dominant in analysis 3 (incremental cost 1242 +/- 73 US dollars, incremental effectiveness -0.57 +/- 0.05 yr). Analysis 4 was comparable to the previously published cost-effectiveness analysis (incremental cost -77 +/- 87 US dollars, incremental effectiveness 0.48 +/- 0.05 yr). CONCLUSIONS: Based on available randomized clinical trial data, nesiritide did not exhibit robust economic superiority over dobutamine. When incorporating the uncertainty (i.e., 95% CIs) in clinical effectiveness as reported in available clinical trial data into the economic analysis, either nesiritide or dobutamine may be the dominant treatment (i.e., more effective at lower cost) for the studied population. Economic analyses of nesiritide and any comparator must account for uncertainty in estimates of cost as well as in clinical effectiveness.

Comparative cost-effectiveness of B-type natriuretic peptide and echocardiography for predicting outcome in patients with congestive heart failure.

Two-dimensional echocardiographic and Doppler variables and B-type natriuretic peptide (BNP) can predict outcomes in patients with congestive heart failure (CHF). However, there is a paucity of data on the relative cost-effectiveness of these modalities in predicting outcome. One hundred sixteen patients hospitalized with CHF underwent simultaneous BNP and Doppler echocardiographic examinations once ready for discharge. The ability of these variables to determine the primary end point (cardiac death or rehospitalization for CHF) was determined. The cost-effectiveness ratios (CER) of 2-dimensional variables, Doppler indexes, and BNP were calculated for prediction of the primary end point. Follow-up was completed in 110 of 116 patients at a mean of 527 days after hospital discharge. Fifty-four patients (50%) reached the primary end point (37 rehospitalizations for CHF and 17 cardiac deaths). When added to a history of admission to the hospital in the preceding year for CHF, a comprehensive Doppler echocardiographic study predicted 52 of 54 events, with a CER of 729.10 dollars, whereas BNP predicted 47 of 54 events (CER 49.98 dollars; p < 0.001 for CER comparison). In patients admitted to hospitals with CHF, predischarge BNP is more cost-effective than comprehensive Doppler echocardiographic examination for the prediction of future cardiac death or rehospitalization for CHF.

Increased cost effectiveness with nesiritide vs. milrinone or dobutamine in the treatment of acute decompensated heart failure.

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.

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.

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.

Intravenous nesiritide in acute heart failure.

The purpose of this study is to evaluate the effect of nesiritide on length of hospital stay, readmission rates, and charges compared with usual care for congestive heart failure (CHF). Using a structured retrospective chart review, we reviewed the records of 127 patients admitted with decompensated CHF, looking at length of stay on initial admission, readmission rates, total hospital days over 3 months, 3-month mortality, pharmacy and hospital charges for the initial admission, and total pharmacy and hospital charges over 3 months. Nesiritide had no effect on initial length of stay, readmission rates, or 3-month mortality. Patients with an ejection fraction >30% who received nesiritide spent more days in the hospital over 3 months than those who received usual care, although there were no differences between the groups in patients with an ejection fraction of < or =30%. Pharmacy and hospital charges for both the initial admission and over 3 months were significantly higher for patients who received nesiritide than for those who received usual care. Patients who received nesiritide incurred significantly higher charges for medical care, but nesiritide did not affect length of stay, readmission rates, or mortality.