Partially hydrolyzed formulas (pHFs) are increasingly used worldwide, both in the prevention of atopic disease in at-risk infants and in the therapeutic management of infants with functional gastrointestinal manifestations. Because prevention is always preferable to treatment, we reviewed the literature aiming to find an answer for the question whether pHF may be recommended for feeding all infants if breast-feeding is not possible. PubMed and Cochrane databases were searched up to December 2014. In addition, to search for data that remained undetected by the searches, we approached authors of relevant articles and major producers of pHFs asking for unpublished data. Because few data were found, nonrandomized, controlled trials and trials in preterm infants were included as well. Overall, only limited data could be found on the efficacy and safety of pHF in healthy term infants. Available data do not indicate that pHFs are potentially harmful for healthy, term infants. With respect to long-term outcomes, particularly referring to immune, metabolic and hormonal effects, data are, however, nonexistent. From a regulatory point of view, pHFs meet the nutrient requirements to be considered as standard formula for term healthy infants. Cost, which is different from country to country, should be considered in the decision-making process. Based on limited available data, the use of pHF in healthy infants is safe with regard to growth. The lack of data, in particular for metabolic consequences and long-term outcomes, is, however, the basis for our recommendation that health authorities should develop and support long-term follow-up studies. Efficacy and long-term safety data are required before a recommendation of this type of formula for all infants can be made.
AIMS: Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality.
METHODS AND RESULTS: Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF.
CONCLUSION: Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.
Objectives: The goal of this study was to explore the association between changes in B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels and risk of hospital admission for heart failure (HF) worsening in patients with chronic HF. Background: The relationship between BNP and NT-proBNP plasma levels and risk of cardiovascular events in patients with chronic HF has been previously demonstrated. However, it is unclear whether changes in BNP and NT-proBNP levels predict morbidity in patients with chronic HF. Methods: The MEDLINE, Cochrane, ISI Web of Science, and SCOPUS databases were searched for papers about HF treatment up to August 2013. Randomized trials enrolling patients with systolic HF, assessing BNP and/or NT-proBNP at baseline and at end of follow-up, and reporting hospital stay for HF were included in the analysis. Meta-regression analysis was performed to test the relationship between BNP and NT-proBNP changes and the clinical endpoint. Sensitivity analysis was performed to assess the influence of baseline variables on results. Egger's linear regression was used to assess publication bias. Results: Nineteen trials enrolling 12,891 participants were included. The median follow-up was 9.5 months (interquartile range: 6 to 18 months), and 22% of patients were women. Active treatments significantly reduced the risk of hospital stay for HF worsening. In meta-regression analysis, changes in BNP and NT-proBNP were significantly associated with risk of hospital stay for HF worsening. Results were confirmed by using sensitivity analysis. No publication bias was detected. Conclusions: In patients with HF, reduction of BNP or NT-proBNP levels was associated with reduced risk of hospital stay for HF worsening.
BACKGROUND: The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF.
METHODOLOGY/PRINCIPAL FINDINGS: MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.509 to 1.035; p = 0.077). [corrected].
CONCLUSIONS/SIGNIFICANCE: Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.
BACKGROUND: The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomised controlled trials (RCTs). However, the benefits have been variable. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on all-cause mortality and HF rehospitalisation in patients with chronic HF.
METHODS: We identified RCTs by systematic search of MEDLINE, EMBASE and the Cochrane Controlled Clinical Trials Register Database. Eligible RCTs were those that enrolled more than 40 patients and involved comparison of BNP-guided versus guideline-guided drug therapy of the patients with chronic HF in the outpatient setting.
RESULTS: Eleven RCTs with a total of 2414 patients and with a mean duration of 12 months (range, 3-36 months) were included in the meta-analysis. Overall, there was a significantly decreased risk of all-cause mortality (relative risk [RR], 0.83; 95% confidence interval [CI], 0.69-0.99; P=0.035; I(2)=0%) and HF rehospitalisation (RR, 0.75; 95% CI, 0.62-0.91; P=0.004; I(2)=62.2%) in the BNP-guided therapy group. Age, baseline BNP are the major dominants of HF rehospitalisation when analysed using meta-regression. In the subgroup analysis, HF rehospitalisation was significantly decreased in the patients younger than 70 years (RR, 0.45; 95% CI, 0.33-0.61; P=0.000; I(2)=0.0%), or with baseline higher BNP (≥2114pg/mL) (RR, 0.53; 95% CI, 0.39-0.72; P=0.000; I(2)=21.8%).
CONCLUSIONS: Compared with usual clinical care, B-type natriuretic peptide-guided therapy reduces all-cause mortality and HF rehospitalisation, especially in patients younger than 70 years or with higher baseline BNP.
OBJECTIVES: To assess the diagnostic accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) for detecting heart failure (HF). To determine whether BNP and NT-proBNP are independent predictors of mortality and morbidity in HF and whether they add to the predictive value of other markers. To ascertain whether treatment guided by BNP or NT-proBNP improves outcomes in HF compared with usual care. To assess the biological variation of BNP and NT-proBNP in HF and non-HF populations.
DATA SOURCES: Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from 1989 to June 2012. Reference lists of included articles, systematic reviews, and gray literature were also searched.
REVIEW METHODS: Studies were evaluated for eligibility and quality, and data were extracted on study design, demographics, diagnostic test characteristics, predictor factors, interventions, outcomes, and test-performance results.
RESULTS: In emergency settings, BNP (51 studies) and NT-proBNP (39 studies) had high sensitivity and low specificity, and were useful for ruling out but less useful for ruling in HF. Similar results were shown in primary care settings for BNP (12 studies) and NT-proBNP (20 studies). The majority of studies assessing prognosis (183 studies) showed associations between BNP and NT-proBNP and all-cause and cardiovascular mortality, morbidity, and composite outcomes across different time intervals in patients with decompensated and chronic stable HF. Most of these were early-phase predictor-finding studies rather than model-validation or impact studies. Incremental predictive value was assessed in decompensated acute HF (7 studies) and chronic HF (15 studies). Almost all studies showed that calibration and discrimination statistics confirmed the added incremental value of BNP and NT-proBNP. Fewer studies used reclassification and model validation computations to establish incremental value. In the general population (seven studies), an association exists between NT-proBNP and mortality (all-cause, cardiovascular, and sudden cardiac) and morbidity (HF and atrial fibrillation). Overall, therapy guided by BNP/NT-proBNP was shown to reduce all-cause mortality but was graded as low strength of evidence. Seven studies assessed biological variation. The difference in serial results was higher for BNP than NT-proBNP, and the index of individuality for BNP and NT-proBNP was very low.
CONCLUSIONS: BNP and NT-proBNP had good diagnostic performance for ruling out HF but were less accurate for ruling in HF. BNP and NT-proBNP had prognostic value in HF and the general population. Therapeutic value was inconclusive. Data on biological variation expressed the differences in results and individuality expected in patients, suggesting that serial measurements need to be interpreted carefully.
Partially hydrolyzed formulas (pHFs) are increasingly used worldwide, both in the prevention of atopic disease in at-risk infants and in the therapeutic management of infants with functional gastrointestinal manifestations. Because prevention is always preferable to treatment, we reviewed the literature aiming to find an answer for the question whether pHF may be recommended for feeding all infants if breast-feeding is not possible. PubMed and Cochrane databases were searched up to December 2014. In addition, to search for data that remained undetected by the searches, we approached authors of relevant articles and major producers of pHFs asking for unpublished data. Because few data were found, nonrandomized, controlled trials and trials in preterm infants were included as well. Overall, only limited data could be found on the efficacy and safety of pHF in healthy term infants. Available data do not indicate that pHFs are potentially harmful for healthy, term infants. With respect to long-term outcomes, particularly referring to immune, metabolic and hormonal effects, data are, however, nonexistent. From a regulatory point of view, pHFs meet the nutrient requirements to be considered as standard formula for term healthy infants. Cost, which is different from country to country, should be considered in the decision-making process. Based on limited available data, the use of pHF in healthy infants is safe with regard to growth. The lack of data, in particular for metabolic consequences and long-term outcomes, is, however, the basis for our recommendation that health authorities should develop and support long-term follow-up studies. Efficacy and long-term safety data are required before a recommendation of this type of formula for all infants can be made.
Systematic Review Question»Systematic review of interventions
