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
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 com...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
NIHR Journals Library
2017-08-01
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| Series: | Health Technology Assessment |
| Subjects: | |
| Online Access: | https://doi.org/10.3310/hta21400 |
| _version_ | 1817989966390624256 |
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| author | Maria Pufulete Rachel Maishman Lucy Dabner Syed Mohiuddin William Hollingworth Chris A Rogers Julian Higgins Mark Dayer John Macleod Sarah Purdy Theresa McDonagh Angus Nightingale Rachael Williams Barnaby C Reeves |
| author_facet | Maria Pufulete Rachel Maishman Lucy Dabner Syed Mohiuddin William Hollingworth Chris A Rogers Julian Higgins Mark Dayer John Macleod Sarah Purdy Theresa McDonagh Angus Nightingale Rachael Williams Barnaby C Reeves |
| author_sort | Maria Pufulete |
| collection | DOAJ |
| description | 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. Trial registration: Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335. 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. |
| first_indexed | 2024-04-14T00:53:07Z |
| format | Article |
| id | doaj.art-f38ea9a7367a4c7ab85d8ff6f58bed51 |
| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-04-14T00:53:07Z |
| publishDate | 2017-08-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Health Technology Assessment |
| spelling | doaj.art-f38ea9a7367a4c7ab85d8ff6f58bed512022-12-22T02:21:42ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242017-08-01214010.3310/hta2140011/102/03Effectiveness 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 modelMaria Pufulete0Rachel Maishman1Lucy Dabner2Syed Mohiuddin3William Hollingworth4Chris A Rogers5Julian Higgins6Mark Dayer7John Macleod8Sarah Purdy9Theresa McDonagh10Angus Nightingale11Rachael Williams12Barnaby C Reeves13Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UKClinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UKClinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UKSchool of Social and Community Medicine, University of Bristol, Bristol, UKSchool of Social and Community Medicine, University of Bristol, Bristol, UKClinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UKSchool of Social and Community Medicine, University of Bristol, Bristol, UKDepartment of Cardiology, Taunton and Somerset NHS Foundation Trust, Taunton, UKSchool of Social and Community Medicine, University of Bristol, Bristol, UKSchool of Social and Community Medicine, University of Bristol, Bristol, UKCardiovascular Division, King’s College London, King’s College Hospital, London, UKDepartment of Cardiology, Bristol Heart Institute, Bristol Royal Infirmary, Bristol, UKClinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency, London, UKClinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UKBackground: 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. Trial registration: Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335. 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.https://doi.org/10.3310/hta21400heart failureb-type natriuretic peptidebnpnt-probnpbnp-guided therapybnp monitoringheart failure reduced ejection fractionhfrefheart failure preserved ejection fractionhfpefsystematic reviewipd meta-analysiscohort studyclinical practice research datalinknational heart failure auditcost-effectiveness model |
| spellingShingle | Maria Pufulete Rachel Maishman Lucy Dabner Syed Mohiuddin William Hollingworth Chris A Rogers Julian Higgins Mark Dayer John Macleod Sarah Purdy Theresa McDonagh Angus Nightingale Rachael Williams Barnaby C Reeves 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 Technology Assessment heart failure b-type natriuretic peptide bnp nt-probnp bnp-guided therapy bnp monitoring heart failure reduced ejection fraction hfref heart failure preserved ejection fraction hfpef systematic review ipd meta-analysis cohort study clinical practice research datalink national heart failure audit cost-effectiveness model |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | heart failure b-type natriuretic peptide bnp nt-probnp bnp-guided therapy bnp monitoring heart failure reduced ejection fraction hfref heart failure preserved ejection fraction hfpef systematic review ipd meta-analysis cohort study clinical practice research datalink national heart failure audit cost-effectiveness model |
| url | https://doi.org/10.3310/hta21400 |
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