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February 25, 2021Clinical Pharmacology & TherapeuticsOpen Access

NT‐proBNP Qualifies as a Surrogate for Clinical End Points in Heart Failure

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Why the study?

NT-proBNP is a well-established biomarker in HF but is controversially discussed as a potential surrogate marker in HF trials.

Does early NT-proBNP measurement predict clinical outcomes in heart failure trials?

Population

108,330 HF patients from real-world data alongside data from 20 clinical HF studies

Comparison

NT-proBNP and mortality/clinical event relationship across real-world data and 20 clinical trials

Design

Hierarchical statistical modeling and validation study using real-world data and clinical trials

Authors

WSWalter SchmittBayer (Germany)HRHauke RühsBayer (Germany)RBRolf BurghausBayer (Germany)

Discussion

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Implication

Early NT-proBNP may enable shorter HF trials; leaves open prospective validation before adoption.

Key Points

  • To evaluate whether early measurements of NT-proBNP can serve as a validated surrogate endpoint to quantitatively predict clinical trial outcomes in heart failure.
  • Analyzed real-world electronic health records from 108,330 heart failure patients in the IBM Watson Health Explorys database alongside aggregate data from 20 clinical heart failure trials using a hierarchical Emax model.
  • Assessed model validity by predicting outcome hazard ratios across five independent phase III heart failure trials using only NT-proBNP measurements taken within 10 weeks of treatment start.
  • The relationship between NT-proBNP and clinical outcomes followed an Emax model with half-maximal risk concentrations (EC50) of 3,880 pg/mL in real-world data and 2,414 pg/mL (IQR 1,460–4,355 pg/mL) across clinical trials, compared to baseline risks of 5.5% and 3.0% (IQR 1.7–4.9%), respectively.
  • Predictions derived solely from short-term NT-proBNP changes (<10 weeks) quantitatively matched the final phase III clinical trial hazard ratios within comparable confidence intervals.

Structured PICO

Does early NT-proBNP measurement predict clinical outcomes in heart failure trials?

P
Population
108,330 heart failure patients from real-world data (IBM Watson Health Explorys database), data from 20 clinical HF studies, and 5 phase III HF studies
I
Intervention
Early NT-proBNP measurement (after short treatment durations of less than 10 weeks)
O
Outcome
Relationship between NT-proBNP and clinical outcome (mortality/clinical events)surrogate

Early NT-proBNP measurement can reliably predict long-term clinical outcomes in heart failure trials, potentially enabling shorter and smaller clinical trials.

Cite This Study

Schmitt et al. (2021) studied this question.

synapsesocial.com/papers/6a1dee78a3f4c58cc935129ehttps://doi.org/10.1002/cpt.2222

Topics

HFrEF treatmentHeart failure
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Prognostic value of NT-proBNP added to clinical parameters to predict two-year prognosis of chronic heart failure patients with mid-range and reduced ejection fraction – A report from FAR NHL prospective registry2019 · 40 citations
  2. 2Clinical Profile and Prognostic Significance of Natriuretic Peptide Trajectory Following Hospitalization for Worsening Chronic Heart Failure: Findings from the ASTRONAUT Trial2015 · 34 citations
  3. 3Spironolactone for Heart Failure with Preserved Ejection Fraction2014 · 2,813 citations
  4. 4Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure2011 · 134 citations
  5. 5Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study2018 · 292 citations