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B-type natriuretic peptide-guided therapy for heart failure (HF): a systematic review and meta-analysis of individual
Maria Pufulete1, Rachel Maishman2, Lucy Dabner2
1Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Level 7, Bristol Royal Infirmary, Queen's Building, Bristol, BS2 8HW, UK. maria.pufulete@bristol.ac.uk.
Insights
Serial B-type natriuretic peptide (BNP) blood testing reduced heart failure (HF) hospitalizations but did not impact mortality. Evidence quality was low to very low, with unclear relevance for general practice.
Area of Science:
- Cardiology
- Clinical Trials
- Evidence Synthesis
Background:
- Heart failure (HF) management often relies on symptom assessment.
- Serial B-type natriuretic peptide (BNP) testing offers a potential biomarker-guided approach.
- Comparing BNP-guided versus symptom-guided therapy is crucial for optimizing HF treatment.
Purpose of the Study:
- To estimate the effectiveness of serial B-type natriuretic peptide (BNP) blood testing for guiding medication up-titration in heart failure (HF) patients.
- To compare BNP-guided therapy against symptom-guided therapy in HF management.
- To analyze outcomes including all-cause mortality, HF-related mortality, hospital admissions, and adverse events.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs).
- Comprehensive literature search across major databases (MEDLINE, Embase, Cochrane Library, Web of Science).
- Random-effects meta-analyses used to estimate hazard ratios (HR) and odds ratios (OR) with confidence intervals (CIs), including individual patient data (IPD) where available.
Main Results:
- BNP-guided therapy significantly reduced hospital admissions for HF by 19% (HR 0.81, 95% CI 0.68 to 0.98).
- No significant reduction was observed in all-cause mortality (HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (OR 0.88, 95% CI 0.67 to 1.16).
- Adverse events were more frequent with BNP-guided therapy (OR 1.29, 95% CI 1.04 to 1.60), with significant interactions for age and ejection fraction on mortality.
Conclusions:
- BNP-guided therapy effectively reduces HF hospitalizations but does not improve mortality outcomes.
- The quality of evidence supporting these findings is predominantly low to very low.
- The clinical applicability of BNP-guided therapy to unselected HF populations, especially those managed by community generalists, remains uncertain.
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 with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83-2.11, patients with heart failure with 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.
Systematic Review Registration:
PROSPERO CRD42013005335.
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