NIHR DC Discover

NIHR Signal Uncertain benefits of BNP blood tests to monitor heart failure treatment

Published on 6 February 2018

doi: 10.3310/signal-000545

In specialist clinics, using B-type natriuretic peptide (BNP) blood levels to guide treatment in people with chronic heart failure shows promise but did not improve survival for all groups. In this review, the benefit was only seen in patients aged less than 75, who survived an extra 1.5 years on average, and possibly those with poor heart function (reduced ejection fraction). However, there was a reduction in hospital admissions for heart failure for everyone.  

BNP is a hormone released from the heart muscle, and higher levels may indicate more severe disease. It is currently used for diagnosis, but its use in monitoring treatment has become the subject of recent research interest.

This research pooled data for 3,074 patients in 13 trials who were randomised to the blood test-guided or symptom-guided therapy and separately studied general practice data for a further 17,095.

The research was limited by the quality of the previous trials, the availability of data and the scarcity of monitored patients in general practice. Furthermore, there was no apparent mechanism found that could explain the small benefit. So, these findings should be regarded as tentative and are not conclusive enough to support a change in practice. Other research is underway that may better define the place for this test.

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Why was this study needed?

Heart failure is a condition where the heart cannot pump blood efficiently enough to meet the needs of the body. It has many causes, commonly, previous heart attack or high blood pressure. The 2010 National Heart Failure Audit estimated that one in 100 people in the UK has heart failure. It has a poor prognosis; around a third of people admitted to hospital with heart failure die within one year. Management currently costs the NHS around £625 million a year. The number of cases is expected to rise with the ageing population.

BNP is released from the heart muscle when it is stretched and under tension. Titrating medication to a pre-defined BNP target is a potential way to optimise treatment. However, it is unclear whether this is better than relying on symptoms alone, particularly in older adults and those with other illnesses.

This programme of work set out to assess the clinical and cost-effectiveness of BNP-guided therapy for people with a new diagnosis of heart failure between January 2007 and March 2013.

What did this study do?

The first part was a systematic review including 13 (non-UK) randomised controlled trials comparing BNP-guided therapy with symptom-based therapy in 3,074 people with heart failure. Five trials had individual patient data available, and most treated to a BNP target. Lack of blinding and variable study methods were common limitations. Younger patients also tended to have poorer heart function, and have fewer other conditions than older patients so may not be representative.

Secondly, a cohort study assessed data for 17,095 patients collected by the general practice Datalink registry and National Heart Failure Audit. Researchers compared people receiving BNP monitoring (regular BNP tests over six month’s observation period or longer), BNP testing (one test or more but not meeting the criteria of regular monitoring) or no testing.

What did it find?

The systematic review found:

  • BNP-guided therapy had no overall effect on risk of death from any cause (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.73 to 1.04). Sub-group analysis found it reduced mortality for participants aged less than 75 years (HR 0.70, 95% CI 0.53 to 0.92) but not for older patients.
  • BNP-guided therapy reduced the risk of hospital admission for heart failure (HR 0.78, 95% CI 0.65 to 0.95) but did not affect overall hospital admission (HR 0.97, 95% CI 0.85 to 1.10).
  • In the cohort study, the overall death rate was 142 patients per 1,000 per year. Death rates were higher in the BNP-monitoring group (187 per 1,000 per year) than in the BNP-testing (131 per 1000) and never-tested groups (144 per 1,000). This probably reflects that this small group were sicker than other patients.

What does current guidance say on this issue?

The 2010 NICE guideline on the management of chronic heart failure recommends that BNP (or its derivative N-terminal pro-Btype natriuretic peptide, NTproBNP) is measured in people with suspected heart failure who have no history of heart attack. Urgent referral and echocardiogram assessment are recommended for those with a BNP level above 400pg/ml. Levels below 100pg/ml are said to make the diagnosis of heart failure unlikely.

Monitoring recommendations include a requirement for regular clinical assessment of functional capacity, fluid status, heart rhythm, cognitive and nutritional status for all patients with chronic heart failure (but not BNP).

What are the implications?

The study does not appear to support a change to clinical practice.

BNP monitoring could be effective for younger patients with reduced ventricular ejection fraction. However, the population with heart failure that is difficult to manage is frequently older and often have other illness besides heart failure.

Trials were conducted in specialist clinics, used a variety of BNP monitoring methods, and did not identify a BNP target to treat. This research is promising, but further evaluation of which people with heart failure might benefit is probably required before this becomes standard practice.

Citation and Funding

Pufulete M, Maishman R, Dabner L, et al. 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. Health Technol Assess. 2017;21(40):1-150.

This project was funded by the National Institute for Health Research (Health Technology Assessment programme) (project number 11/102/03) and special project grants from the British Heart Foundation, a National Institute for Health Research Methodology Research Fellowship and the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust.

Bibliography

British Heart Foundation. Heart Failure. London: British Heart Foundation; 2017.

NHS Information Centre. National Heart Failure Audit. Leeds: The Clinical Audit Support Unit; The Information Centre for health and social care; 2010. 

NICE. Chronic heart failure in adults: management. CG108. London: National Institute for Health and Care Excellence; 2010.

Why was this study needed?

Heart failure is a condition where the heart cannot pump blood efficiently enough to meet the needs of the body. It has many causes, commonly, previous heart attack or high blood pressure. The 2010 National Heart Failure Audit estimated that one in 100 people in the UK has heart failure. It has a poor prognosis; around a third of people admitted to hospital with heart failure die within one year. Management currently costs the NHS around £625 million a year. The number of cases is expected to rise with the ageing population.

BNP is released from the heart muscle when it is stretched and under tension. Titrating medication to a pre-defined BNP target is a potential way to optimise treatment. However, it is unclear whether this is better than relying on symptoms alone, particularly in older adults and those with other illnesses.

This programme of work set out to assess the clinical and cost-effectiveness of BNP-guided therapy for people with a new diagnosis of heart failure between January 2007 and March 2013.

What did this study do?

The first part was a systematic review including 13 (non-UK) randomised controlled trials comparing BNP-guided therapy with symptom-based therapy in 3,074 people with heart failure. Five trials had individual patient data available, and most treated to a BNP target. Lack of blinding and variable study methods were common limitations. Younger patients also tended to have poorer heart function, and have fewer other conditions than older patients so may not be representative.

Secondly, a cohort study assessed data for 17,095 patients collected by the general practice Datalink registry and National Heart Failure Audit. Researchers compared people receiving BNP monitoring (regular BNP tests over six month’s observation period or longer), BNP testing (one test or more but not meeting the criteria of regular monitoring) or no testing.

What did it find?

The systematic review found:

  • BNP-guided therapy had no overall effect on risk of death from any cause (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.73 to 1.04). Sub-group analysis found it reduced mortality for participants aged less than 75 years (HR 0.70, 95% CI 0.53 to 0.92) but not for older patients.
  • BNP-guided therapy reduced the risk of hospital admission for heart failure (HR 0.78, 95% CI 0.65 to 0.95) but did not affect overall hospital admission (HR 0.97, 95% CI 0.85 to 1.10).
  • In the cohort study, the overall death rate was 142 patients per 1,000 per year. Death rates were higher in the BNP-monitoring group (187 per 1,000 per year) than in the BNP-testing (131 per 1000) and never-tested groups (144 per 1,000). This probably reflects that this small group were sicker than other patients.

What does current guidance say on this issue?

The 2010 NICE guideline on the management of chronic heart failure recommends that BNP (or its derivative N-terminal pro-Btype natriuretic peptide, NTproBNP) is measured in people with suspected heart failure who have no history of heart attack. Urgent referral and echocardiogram assessment are recommended for those with a BNP level above 400pg/ml. Levels below 100pg/ml are said to make the diagnosis of heart failure unlikely.

Monitoring recommendations include a requirement for regular clinical assessment of functional capacity, fluid status, heart rhythm, cognitive and nutritional status for all patients with chronic heart failure (but not BNP).

What are the implications?

The study does not appear to support a change to clinical practice.

BNP monitoring could be effective for younger patients with reduced ventricular ejection fraction. However, the population with heart failure that is difficult to manage is frequently older and often have other illness besides heart failure.

Trials were conducted in specialist clinics, used a variety of BNP monitoring methods, and did not identify a BNP target to treat. This research is promising, but further evaluation of which people with heart failure might benefit is probably required before this becomes standard practice.

Citation and Funding

Pufulete M, Maishman R, Dabner L, et al. 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. Health Technol Assess. 2017;21(40):1-150.

This project was funded by the National Institute for Health Research (Health Technology Assessment programme) (project number 11/102/03) and special project grants from the British Heart Foundation, a National Institute for Health Research Methodology Research Fellowship and the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust.

Bibliography

British Heart Foundation. Heart Failure. London: British Heart Foundation; 2017.

NHS Information Centre. National Heart Failure Audit. Leeds: The Clinical Audit Support Unit; The Information Centre for health and social care; 2010. 

NICE. Chronic heart failure in adults: management. CG108. London: National Institute for Health and Care Excellence; 2010.

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

Published on 4 August 2017

Pufulete M, Maishman R, Dabner L, Mohiuddin S, Hollingworth W, Rogers C A, Higgins J, Dayer M, Macleod J, Purdy S, McDonagh T, Nightingale A, Williams R & Reeves B C.

Health Technology Assessment Volume 21 Issue 40 , 2017

Background Heart 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. Objective To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients. Design Systematic review, cohort study and cost-effectiveness model. Setting A 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. Interventions Systematic review: BNP-guided therapy or symptom-guided therapy in primary or secondary care. Cohort study: BNP monitored (≥ 6 months’ follow-up and three or more BNP tests and two 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 measures Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model. Data sources Systematic 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 methods A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs. Results Five 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. Limitations The 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. Conclusions The 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 work Identify 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. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health 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.

Expert commentary

NICE guidance recommends the measurement of BNP in patients with new-suspected heart failure; further, plasma NP levels normally fall after treatment. It is tempting to think outcomes for patients with heart failure might be improved by titrating treatment to BNP levels.

However, we have several “don’t knows”: 1) the appropriate target BNP; 2) what intervention should be altered; 3) should BNP monitoring be applied in all types of heart failure; 4) is BNP monitoring cost effective.

To date, there is insufficient clarity on these questions to recommend BNP monitoring in heart failure.

Iain Squire, Professor of Cardiovascular Medicine, University of Leicester, NIHR Biomedical Research Centre, Glenfield Hospital, Leicester