B-type natriuretic peptide-guided therapy for heart failure (HF): a systematic review and meta-analysis of individual participant data (IPD) and aggregate data

Maria Pufulete*, Rachel Maishman, Lucy Dabner, Julian Higgins, Chris Rogers, Mark Dayer, John Macleod, Sarah Purdy, William Hollingworth, Morten Schou, Manuel Anguita-Sanchez, Patric Karlström, Michael Kleiner Shochat, Theresa McDonagh, Angus Nightingale, Barnaby Reeves

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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BACKGROUND: We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF). METHODS: Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: Medline (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 Week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI. RESULTS: We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and: age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53-0.92, patients <75 years old and HR 1.07, 95% CI 0.84-1.37, patients ≥75 years old); ejection fraction (p=0.026, 11 RCTs; HR 0.84, 95% CI 0.71-0.99, patients with heart failure reduced ejection fraction, HFrEF; and HR 1.33, 95% CI 0.83-2.11, patients with heart failure preserved ejection fraction, HFpEF). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60). CONCLUSION: BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear.
Original languageEnglish
Article number112
Number of pages21
JournalSystematic Reviews
Publication statusPublished - 31 Jul 2018

Structured keywords

  • Bristol Heart Institute
  • Centre for Surgical Research
  • BTC (Bristol Trials Centre)


  • B-type natriuretic peptide
  • Heart failure
  • IPD meta-analysis
  • Systematic review


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  • NIHR BRC Cardiovascular

    Angelini, G. D.


    Project: Research, Parent

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