Biomarker-guided therapy reduced all-cause mortality by 16% compared to clinical guidance in heart failure patients, though this benefit lost significance when restricted to high-quality trials.
Meta-Analysis (n=5,069)
Does biomarker-guided treatment (BNP or NT-proBNP) reduce all-cause mortality and HF-related hospitalizations in adult patients with heart failure compared to clinically guided standard care?
Although initial pooled estimates suggest a mortality and hospitalization benefit with biomarker-guided HF therapy, the evidence is of very low quality and driven by biased studies, indicating it should not be routinely implemented.
Effect estimate: RR 0.84 (95% CI 0.73-0.96)
Absolute Event Rate: 18% vs 21.4%
p-value: p=0.015
Background: The clinical value of B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy for improving outcomes in patients with heart failure (HF) remains controversial. Thus, this meta-analysis synthesizes the available evidence from randomized controlled trials (RCTs) to determine whether a biomarker-guided strategy reduces all-cause mortality and HF-related hospitalizations compared with clinically guided management. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science databases from inception to May 2025 for RCTs comparing biomarker-guided versus clinically guided management in patients with HF. Pooled risk ratios (RRs) were calculated using a random-effects model. We performed extensive supplementary analyses, including a subgroup analysis, sensitivity analysis, and trial sequential analysis (TSA). Results: We included 17 articles (reporting on 17 distinct RCTs) comprising 5069 patients. The primary meta-analysis showed that biomarker-guided therapy was associated with a significant reduction in all-cause mortality (RR 0.84, 95% confidence interval (CI) 0.73–0.96; I2 = 12.2%) and HF-related hospitalizations (RR 0.79, 95% CI 0.65–0.96; I2 = 53.7%). However, the robustness of these findings was undermined by subsequent analyses. Meanwhile, a sensitivity analysis restricted to studies with a low risk of bias rendered the mortality benefit non-significant (RR 0.90, 95% CI 0.79–1.03). Egger's test indicated potential publication bias (p = 0.0285), and TSA suggested the cumulative evidence was insufficient to draw a definitive conclusion. Conclusions: Although there is a trend toward benefit, the existing evidence for biomarker-guided HF therapy is deemed “very low” quality based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment. The results were compromised by methodological deficiencies in primary studies and potential publication bias. Therefore, the evidence is inadequate to support the routine use of this strategy in clinical practice. Further large-scale, high-quality RCTs are warranted. The PROSPERO Registration: CRD420250652134, https://www.crd.york.ac.uk/PROSPERO/view/CRD420250652134.
Zhou et al. (2026) conducted a meta-analysis in Heart failure (n=5,069). Biomarker-guided therapy (BNP or NT-proBNP) vs. Clinically guided standard care was evaluated on All-cause mortality (RR 0.84, 95% CI 0.73-0.96, p=0.015). Biomarker-guided therapy reduced all-cause mortality by 16% compared to clinical guidance in heart failure patients, though this benefit lost significance when restricted to high-quality trials.