Primary studies included in this systematic review

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Journal European journal of heart failure
Year 2010
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Aims Treatment of chronic heart failure (CHF) guided by natriuretic peptides has been studied in clinical trials with conflicting results. The aim of this study was to investigate if N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy in symptomatic heart failure patients in primary care would improve clinical outcomes over and above treatment according to guidelines. Methods and results SIGNAL-HF was a 9 month, randomized, single-blind, parallel group study in patients with CHF in NYHA class II-IV, ejection fraction (EF) <50 and elevated NT-proBNP levels (males >800, females >1000 ng/L). All investigators underwent a pre-study educational programme about current CHF guidelines. A control group managed by non-trained investigators was considered not possible for ethical and practical reasons. Patients were randomized to structured treatment of CHF according to guidelines with or without NT-proBNP monitoring. The choice and dose of therapy for CHF was at the investigator's discretion. The primary outcome variable was the composite endpoint of days alive, days out of hospital, and symptom score from the Kansas City Cardiomyopathy Questionnaire.In all, 252 patients were randomized. The allocation groups were well balanced with regards to age, NT-proBNP, and EF. Treatment doses of beta-blockers and blockers of the renin-angiotensin-aldosterone system were markedly increased towards target doses and to a similar degree in both groups. There were no differences between the groups concerning either the primary endpoint (P = 0.28) or its components [cardiovascular (CV) death, P = 0.93; CV hospitalization, P = 0.88; or symptom score, P = 0.28].Conclusion NT-proBNP-guided CHF treatment did not result in important improvements in clinical outcomes in patients with CHF in primary care above and beyond what could be achieved by education and structured CHF treatment according to guidelines. © 2010 Author.

Primary study

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Journal Annual Scientific Meeting of American College of Cardiology
Year 2009
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Journal JAMA : the journal of the American Medical Association
Year 2009
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Context It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy. Objective To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy. Design, Setting, and Patients Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction ≤45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times theupper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008. Intervention Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy). Main Outcome Measures Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires. Results Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P =.39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P =.01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction) Conclusion Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment. Trial Registration isrctn.org Identifier: ISRCTN43596477 © 2009 American Medical Association. All rights reserved.

Primary study

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Journal Circulation
Year 2008
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Primary study

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Journal Journal of the American College of Cardiology
Year 2007
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OBJECTIVES: The aim of this multicenter study was to evaluate the prognostic impact of a therapeutic strategy using plasma brain natriuretic peptide (BNP) levels. BACKGROUND: The prognosis of chronic heart failure (CHF) remains poor, even among patients treated in specialized departments. METHODS: A total of 220 New York Heart Association functional class II to III patients considered optimally treated with angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, and diuretics by CHF specialists were randomized to medical treatment according to either current guidelines (clinical group) or a goal of decreasing BNP plasma levels <100 pg/ml (BNP group). Outpatient visits were scheduled every month for 3 months, then every 3 months. The primary combined end point was CHF-related death or hospital stay for CHF. RESULTS: Both groups were similar for baseline clinical and biological characteristics. Left ventricular ejection fraction was slightly lower in the BNP group than in the clinical group (29.9 +/- 7.7% vs. 31.8 +/- 8.4%, p = 0.05). At the end of the first 3 months, all types of drugs were changed more frequently in the BNP group. Mean dosages of ACEIs and beta-blockers were significantly higher in the BNP group (p < 0.05), whereas the mean increase in furosemide dosage was similar in both groups. During follow-up (median 15 months), significantly fewer patients reached the combined end point in the BNP group (24% vs. 52%, p < 0.001). CONCLUSIONS: In optimally treated CHF patients, a BNP-guided strategy reduced the risk of CHF-related death or hospital stay for CHF. The result was mainly obtained through an increase in ACEI and beta-blocker dosages.

Primary study

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Journal Journal of investigational allergology & clinical immunology
Year 2006
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BACKGROUND: Hydrolyzed formulas used to feed infants with cow's milk-allergy can be classified as soy based, extensively hydrolyzed (casein, whey and mixed), and amino-acid based. Their unsatisfactory taste is reported by parents and physicians. OBJECTIVE: The aim of this study was to ascertain the palatability of these formulas in a double-blind taste test. MATERIALS AND METHODS: Fifty healthy volunteers performed a randomized-order double-blind test with 12 different milks. The taste, smell, smell, and texture of each formula were evaluated o n scales ranging from 1 (worst) t o 5 (best). The Pearson correlation coefficient between the peptide weight of each formula and the score obtained for each evaluated attribute was calculated. RESULTS: The soy formulas and rice formula had the best taste scores, followed by the whey hydrolysates; the mixed hydrolysates and the casein hydrolysates had the lowest taste scores. Individually the most palatable formula was mixed hydrolysate 1, by total score. We found a statistically significant correlation between peptide weight, reflecting the degree of hydrolysis of each formula, and the scores obtained for taste, texture, and overall palatability. CONCLUSION: The palatability of formulas is determined by the amount of bitter peptides obtained through hydrolysis. Flavorings and sweeteners may also contribute to palatability. Further studies are needed in order to determine how to modify the organoleptic properties of these products with the purpose of improving their palatability.

Primary study

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Journal Congestive heart failure (Greenwich, Conn.)
Year 2005
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B-type natriuretic peptide (BNP) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure. Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels. The aim of this study is to compare the efficacy of a BNP-guided approach vs. standard care on beta-blocker titration in heart failure patients. Forty-one patients with heart failure were randomized into a clinical trial. Bisoprolol was started, and the dose was regularly up-titrated. BNP was measured monthly. The clinical group had beta-blocker dosage increased according to standard care, whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus standard care. The primary outcome was mean beta-blocker dose achieved after 3 months. BNP levels, left ventricular ejection fraction, clinical score, quality of life, and hospitalization were collected in all patients. BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD (5.9+/-4.3 mg vs. 4.4+/-3.4 mg, p=0.22). Left ventricular ejection fraction was significantly improved in both groups by 7.3% (95% confidence interval, 4.1%-10.4%; p<0.0001). A trend toward better quality of life was seen in the BNP group.

Primary study

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Journal Lancet
Year 2000
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<b>BACKGROUND: </b>There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure. We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide (N-BNP) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen.<b>METHODS: </b>69 patients with impaired systolic function (left-ventricular ejection fraction &lt;40%) and symptomatic heart failure (New York Heart Association class II-IV) were randomised to receive treatment guided by either plasma N-BNP concentration (BNP group) or standardised clinical assessment (clinical group).<b>FINDINGS: </b>During follow-up (minimum 6-months, median 9.5 months), there were fewer total cardiovascular events (death, hospital admission, or heart failure decompensation) in the BNP group than in the clinical group (19 vs 54, p=0.02). At 6 months, 27% of patients in the BNP group and 53% in the clinical group had experienced a first cardiovascular event (p=0.034). Changes in left-ventricular function, quality of life, renal function, and adverse events were similar in both groups.<b>INTERPRETATION: </b>N-BNP-guided treatment of heart failure reduced total cardiovascular events, and delayed time to first event compared with intensive clinically guided treatment.