NT-proBNP-Guided Preemptive Treatment of Outpatients With Chronic Heart Failure Followed in a out Hospital Clinic

Shochat, Michael; Shotan, Avraham; Kazatsker, Mark; Asif, Aya; Dahan, Iris; Shochat, Ilia; Levy, Yaniv; Blondheim, David

doi:10.1016/j.cardfail.2012.06.198

Cited by 3 publications

(16 citation statements)

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“…Of the three studies with good allocation concealment, only two 52,59,60 provided data on all-cause hospitalisations and the SA was not performed. [53][54][55][56] Across these studies, 245 out of 882 patients in the BNP groups (28%) were hospitalised for HF at least once, compared with 311 out of 879 patients (35%) in the symptom-guided therapy groups. In a meta-analysis of the effect of BNP-guided therapy on the hazard of hospitalisation as a result of HF, BNP-guided therapy reduced the hazard (four RCTs provided IPD [53][54][55][56] and eight provided aggregate data; [58][59][60][61][62][63][64][65][66] HR 0.78, 95% CI 0.65 to 0.95) ( Figure 5).…”

Section: Secondary Outcomesmentioning

confidence: 99%

“…Ten out of 13 RCTs (77%) [52][53][54][55]59,[61][62][63]65,66 were rated as having a high risk of bias in at least one domain. Three out of 13 RCTs (23%) 56,58,64 were rated as having unclear risk of bias; one of these studies 56 provided IPD but no study protocol and was published as an abstract only, so its risk of bias could not be fully assessed. The main factor that contributed to having a high risk of bias was the lack of blinding (of participants and care-giving clinicians), which could lead to differential departure from the intended intervention (performance bias).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Across six RCTs [52][53][54][55][56]59,60 with data on all-cause hospitalisation, a total of 285 out of 493 patients (58%) in the BNP group had at least one hospital admission, compared with 281 out of 491 patients (57%) in the control group. BNP-guided therapy did not reduce the hazard of hospitalisation from any cause (HR 0.97, 95% CI 0.85 to 1.10) (Figure 4).…”

Section: Secondary Outcomesmentioning

confidence: 99%

“…55,56 Of the 11 RCTs that used a BNP-lowering strategy, eight set a single target (BNP 100-300 pg/ml; NT-proBNP 400-2200 pg/ml), 53,54,58,59,61,[64][65][66] two of which stratified by age (< 75 years and ≥ 75 years), 54,59 and three set an individual BNP target (BNP level at discharge, reduction of 50% from baseline). 52,62,63 Treatment algorithms in the BNP group differed slightly between studies but all were based on stepwise titration of therapy according to clinical guidelines.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Of the 13 studies included in the meta-analysis, eight were conducted in Europe (none in the UK), [53][54][55]59,[61][62][63]65 two were conducted in New Zealand, 58,64 two were conducted in North America 52,66 and one was conducted in Israel. 56 Only one RCT 63 [Swedish Intervention study -Guidelines and NT-proBNP AnaLysis in Heart Failure (SIGNAL-HF)] was conducted in primary care; 12 were conducted in hospital HF clinics, with most of these recruiting patients during or straight after hospitalisation for HF. Two different types of BNP-guided therapy were identified.…”

Section: Systematic Review and Meta-analysismentioning

confidence: 99%

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Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model

Pufulete

Maishman

Dabner

et al. 2017

Health Technol Assess

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BackgroundHeart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients.DesignSystematic review, cohort study and cost-effectiveness model.SettingA literature review and usual care in the NHS.Participants(a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS.InterventionsSystematic review: BNP-guided therapy or symptom-guided therapy in primary or secondary care.Cohort study: BNP monitored (≥ 6 months’ follow-upandthree or more BNP testsandtwo or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested.Cost-effectiveness model: BNP-guided therapy in specialist clinics.Main outcome measuresMortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model.Data sourcesSystematic review: Individual participant or aggregate data from eligible RCTs.Cohort study: The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA).Review methodsA systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs.ResultsFive RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged < 75 years or who had heart failure with a reduced ejection fraction (HFrEF) received the most benefit [interactions (p = 0.03): < 75 years vs. ≥ 75 years: HR 0.70 (95% CI 0.53 to 0.92) vs. 1.07 (95% CI 0.84 to 1.37); HFrEF vs. heart failure with a preserved ejection fraction (HFpEF): HR 0.83 (95% CI 0.68 to 1.01) vs. 1.33 (95% CI 0.83 to 2.11)]. In the cohort study, incident HF patients (1 April 2005–31 March 2013) were never tested (n = 13,632), BNP tested (n = 3392) or BNP monitored (n = 71). Median survival was 5 years; all-cause mortality was 141.5 out of 1000 person-years (95% CI 138.5 to 144.6 person-years). All-cause mortality and hospital admission rate were highest in the BNP-monitored group, and median survival among 130,433 NHFA patients (1 January 2007–1 March 2013) was 2.2 years. The admission rate was 1.1 patients per year (interquartile range 0.5–3.5 patients). In the cost-effectiveness model, in patients aged < 75 years with HFrEF or HFpEF, BNP-guided therapy improves median survival (7.98 vs. 6.46 years) with a small QALY gain (5.68 vs. 5.02) but higher lifetime costs (£64,777 vs. £58,139). BNP-guided therapy is cost-effective at a threshold of £20,000 per QALY.LimitationsThe limitations of the trial were a lack of IPD for most RCTs and heterogeneous interventions; the inability to identify BNP monitoring confidently, to determine medication doses or to distinguish between HFrEF and HFpEF; the use of a simplified two-state Markov model; a focus on health service costs and a paucity of data on HFpEF patients aged < 75 years and HFrEF patients aged ≥ 75 years.ConclusionsThe efficacy of BNP-guided therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients aged < 75 years with HFrEF. The evidence reviewed may not apply in the UK because care is delivered differently.Future workIdentify an optimal BNP-monitoring strategy and how to optimise HF management in accordance with guidelines; update the IPD meta-analysis to include the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) RCT; collect routine long-term outcome data for completed and ongoing RCTs.Trial registrationCurrent Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 40. See the NIHR Journals Library website for further project information. The British Heart Foundation paid for Chris A Rogers’ and Maria Pufulete’s time contributing to the study. Syed Mohiuddin’s time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust. Rachel Maishman contributed to the study when she was in receipt of a NIHR Methodology Research Fellowship.

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Section: Secondary Outcomesmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Secondary Outcomesmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Systematic Review and Meta-analysismentioning

confidence: 99%

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Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model

Pufulete

Maishman

Dabner

et al. 2017

Health Technol Assess

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B-type natriuretic peptide-guided treatment for heart failure

McLellan

Heneghan

Perera

et al. 2016

Cochrane Database of Systematic Reviews

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Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT‐proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP‐guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow‐up. Adults treated for heart failure, in both in‐hospital and out‐of‐hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP‐guided treatment with clinical assessment alone. The evidence for all‐cause mortality using NP‐guided treatment showed uncertainty (RR 0.87, 95% CI 0...

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Essential components in natriuretic peptide-guided management of heart failure: an intervention synthesis

et al. 2018

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AimTo identify the key components of natriuretic peptide (NP)-guided treatment interventions which reduced hospitalisation in patients with heart failure (HF).Methods and resultsWe extracted detailed information on the components of interventions from studies of NP-guided treatment of HF identified in a previous systematic review. We used meta-regression techniques to assess univariate associations between components and the strength of the reduction in HF hospitalisations and all-cause mortality. A Bayesian meta-analysis approach was used to re-estimate study-level effects in order to identify the study with the most effective NP-guided monitoring intervention. Finally, we examined the intervention options common to the studies in which the 95% credible interval excluded no effect. We identified eight components of NP-guided treatment from ten studies. Univariate comparisons produced mainly equivocal results, but single trial choice and common components analysis led to similar conclusions. Using a predefined treatment protocol, setting a stringent NP target (N-terminal pro-B-type natriuretic peptide of 1000 pg/mL or B-type natriuretic peptide 100 pg/mL) and including a relative targetwere potential key components to reducing HF hospitalisations using NP-guided therapy.ConclusionThis analysis provides a description of the key components of NP-guided treatment which could help policy makers develop specific recommendations for HF management. Our research suggests that NP-guided interventions could be simplified, but more research in relevant health settings, such as primary care, is required.

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NT-proBNP-Guided Preemptive Treatment of Outpatients With Chronic Heart Failure Followed in a out Hospital Clinic

Cited by 3 publications

References 0 publications

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model

B-type natriuretic peptide-guided treatment for heart failure

Essential components in natriuretic peptide-guided management of heart failure: an intervention synthesis

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