B-type natriuretic peptide-guided treatment for heart failure patients

Review question

We aimed to discover whether using B-type natriuretic-guided treatment or a health plan alone is more effective for managing patients with heart failure.


Heart failure is a complex condition that occurs when the heart does not pump blood effectively enough to meet the needs of the body. It is caused by a range of diseases that impair the structure and function of the heart and may result in breathlessness, fatigue and fluid retention. People with heart failure are frequently users of general practice and hospitals, particularly as inpatients. Furthermore, they have reduced life expectancy, although medicines and other treatments can improve the chance of survival.

B-type natriuretic peptide (NP) is a substance produced in the heart. The measurement of NP can be used to indicate the condition of the heart. For some time, NP has been used for diagnosing heart failure and predicting what is likely to happen. We wanted to discover if NP may also offer a way to manage and make the best use of medicines.

Study selection and characteristics

We carried out a review of all studies and the evidence is current to 15 March 2016. We found 18 studies of NP-guided treatment in which 3660 patients with heart failure took part. Patients were between 62 to 80 years old at the start of the studies. The duration of each study ranged from one to 54 months.

Eight out of the 18 studies were part or fully funded by pharmaceutical companies, one was funded by a national research body, five were partially funded either by national research grants, lotteries, hospital funds and/or pharmaceutical companies and four studies did not report the funding source.

Key results

The evidence was unclear as to whether number of deaths from any cause varied between patients with heart failure using NP-guided treatment compared with those using a health plan alone. Nor was it clear as to whether there were less deaths when the results were separated into patients older or younger than 75 years old (age results only included three studies). Furthermore, we found that the evidence was unclear whether the number of deaths from heart failure alone varied between the NP-guided treatment or health plan alone groups.

We found that hospital admission due to heart failure may be reduced in the patients using NP-guided treatment compared with a health plan alone. Based on these results we would expect that out of 1000 patients with heart failure who are guided by a health plan alone, 377 would experience an admission to hospital due to heart failure. Whereas, between 230 and 301 patients would experience an admission to hospital due to heart failure if they received NP-guided treatment. However, the evidence was unclear as to whether the numbers of hospital admission from any cause were affected.

There was limited information about either harms to patients, or the cost of the treatment. It was not possible to combine the results from these studies for these outcomes. However, four of the six studies commented that they found no difference in harms or less difference in harms between the patients using NP-guided treatment compared with a health plan alone, the other two studies did not comment. Four studies reported results on costs, three of these reported there may be lower costs in the NP-guided treatment groups compared with health plan groups. Lower costs appeared to be due to less cost for hospital stays. However, one study reported that NP-guided treatment was unlikely to be cost-effective.

The evidence was unclear as to if a benefit was shown in the replies to quality-of-life surveys when comparing between NP-guided treatment and health plan only groups.

Quality of evidence

Overall evidence for death from all causes, from heart failure alone and for hospital admission was of low quality. For harm to patients and cost outcomes the quality of evidence was low, whilst evidence for patients' quality of life surveys was very low. For all outcomes there was little evidence due to the way the studies were conducted. In addition, for harm to patients and cost of treatment there were differences in the type of information available.

Authors' conclusions: 

In patients with heart failure low-quality evidence showed a reduction in heart failure admission with NP-guided treatment while low-quality evidence showed uncertainty in the effect of NP-guided treatment for all-cause mortality, heart failure mortality, and all-cause admission. Uncertainty in the effect was further shown by very low-quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.

Read the full abstract...

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.


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 strategy: 

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 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence).

The evidence suggested heart failure admission was reduced by NP-guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all-cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence).

Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP-guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD -0.03, 95% CI -1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence).

We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies.

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