The Minimal Important Difference in N-Terminal Pro-Brain Natriuretic Peptide in Pulmonary Hypertension.
retrospective_cohort · Level III
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- Record sourced from PubMed, PMID 41802593.
- Also identified by DOI 10.1016/j.chest.2026.02.014.
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Abstract
N-terminal pro-brain natriuretic peptide (NT-proBNP) is a commonly used biomarker of right-sided heart function in patients with pulmonary hypertension. What is the minimal important difference (MID) for NT-proBNP change in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension related to interstitial lung disease (PH-ILD), and is achievement of the MID associated with improved clinical outcomes? Data from 2 placebo-controlled trials were used to determine the MID for PAH (FREEDOM-EV: oral treprostinil) and PH-ILD (INCREASE: inhaled treprostinil). Distributional-based methods were used to calculate the MID for percent change from baseline in NT-proBNP in the FREEDOM-EV and INCREASE trials at 12 and 16 weeks, respectively. The associations between MID achievement and clinical outcomes were assessed by occurrence of a clinical worsening event in FREEDOM-EV or 6-minute walk distance improvement in INCREASE. Complete data were available for 638 participants in FREEDOM-EV and 250 participants in INCREASE. The median MID for NT-proBNP change in the FREEDOM-EV and INCREASE trials was a 48% improvement. Participants with PAH who achieved the MID at 12 weeks were 52% less likely to have a clinical worsening event during long-term follow-up (hazard ratio, 0.48; 95% CI, 0.31-0.75; P = .001). Participants with PH-ILD who achieved the MID at 16 weeks had a relative improvement in 6-minute walk distance of 40 m (95% CI, 14-66 m; P = .003) compared with those who did not achieve the MID. Our results show the estimated MID for short-term NT-proBNP improvement in PAH and PH-ILD is remarkably similar at 48%. Achievement of the MID for NT-proBNP change is strongly associated with clinically important outcomes in both PAH and PH-ILD, demonstrating that measuring NT-proBNP change over 12 to 16 weeks can be informative for prognosis and may be useful for decisions regarding treatment escalation in individuals with PAH and PH-ILD.