Projects per year
Objective(s) To evaluate the effectiveness and cost-effectiveness of BNP-guided therapy compared to symptom-guided therapy in HF patients.
Design Systematic review, cohort study and cost-effectiveness model.
Setting Literature review and usual care in the NHS.
Participants HF patients in randomised controlled trials (RCTs) of BNP-guided-therapy and the NHS.
InterventionsReview: BNP-guided-therapy or symptom-guided therapy in primary or secondary care.Cohort: BNP-monitored (≥6 months follow-up AND ≥3 BNP tests AND ≥2 tests/year), BNP-tested (≥1 test but not BNP-monitored) or never tested. Cost-effectiveness model: BNP-guided-therapy in specialist clinics.
Main outcome measures Mortality and hospital admission (all-cause and HF-related), adverse events; quality-adjusted life years (QALYs) for the cost-effectiveness model.
Data sources Review: Individual participant or aggregate data from eligible RCTs.Cohort: Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES) and National Heart Failure Audit (NHFA).
Review methodsSystematic literature search (five databases; trial registries; grey literature; reference lists of publications) for published and unpublished RCTs.
ResultsReview: Five RCTs contributed individual participant data (IPD) and 8 aggregate data (1563 participants randomized to BNP-guided-therapy and 1538 to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided-therapy was 0.87 (95% confidence interval (CI) 0.73-1.04). Patients <75 years or with reduced ejection fraction (EF) benefited most (interactions, p=0.03; <75 years, HR=0.70, 95% CI 0.53-0.92 versus ≥75 years, HR=1.07, 95% CI 0.84-1.37; reduced EF HR=0.83, 95% CI 0.68-1.01 versus preserved EF, HR=1.33, 95% CI 0.83-2.11).Cohort: Incident HF patients (01/04/2005–31/03/2013) were: never tested (n=13632), BNP-tested (n=3392) or BNP-monitored (n=71). Median survival was 5 years; all-cause mortality was 141.5/1000 person years (95% CI, 138.5-144.6). All-cause mortality and hospital admission rate were highest in the BNP-monitored group.130,433 NHFA patients (01/01/2007–01/03/2013) had median survival 2.2 years. The admission rate was 1.1/year (IQR 0.5, 3.5). Cost-effectiveness model: In patients <75 years with HFrEF or HFpEF, BNP-guided-therapy improves median survival (7.98 years versus 6.46 years) with a small QALY gain (5.68 versus 5.02) but higher lifetime costs (£64,777 versus £58,139). BNP-guided-therapy is cost-effective at a £20,000/QALY threshold.
LimitationsReview: lack of IPD for most RCTs; heterogeneous interventions.Cohort: inability to identify BNP-monitoring confidently, determine medication doses or distinguish HFrEF and HFpEF. Cost-effectiveness model: simplified two-state Markov model; focus on health service costs; paucity of data about HFpEF patients <75 years and HFrEF patients ≥75 years.
ConclusionsThe efficacy of BNP-guided-therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients <75 years of age 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 GUIDE-IT RCT; collect routine long-term outcome data for completed and ongoing RCTs.
Review and cohort study registrationPROSPERO 2013: CRD42013005335ISRCTN37248047
Funding detailsNIHR Health Technology Assessment programme, ref 11/103/03.
- BTC (Bristol Trials Centre)
- Centre for Surgical Research
- Bristol Heart Institute
- Heart failure
- B-type natriuretic peptide
- BNP-guided therapy
- IPD meta-analysis
- cohort study
- Clinical Practice Research Datalink (CPRD)
- cost effectiveness model.
- BNP monitoring
- heart failure reduced ejection fraction
- heart failure preserved ejection fraction
- systematic review
- National Heart Failure Audit