The Minimal Important Difference in N-Terminal Pro-Brain Natriuretic Peptide in Pulmonary Hypertension.

research_question

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?

在肺动脉高压（PAH）和间质性肺疾病相关的肺动脉高压（PH-ILD）患者中，NT-proBNP变化的最小重要差异（MID）是多少，达到MID是否与改善的临床结果相关？

study_design_and_methods

Data from 2 placebo-controlledtrials were used to determine the MID for PAH (Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy [FREEDOM-EV]: oral treprostinil) and PH-ILD (Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE [INCREASE]: inhaled treprostinil).

使用了两项安慰剂对照试验的数据来确定PAH（接受背景口服单一疗法的PAH患者UT-15C的III期临床恶化研究[FREEDOM-EV]：口服曲前列环素）和PH-ILD（包括CPFE的成人PH与ILD的吸入曲前列环素的安全性和有效性研究[INCREASE]：吸入曲前列环素）的最小临床重要差异（MID）。

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.

使用分布基础方法计算了在FREEDOM-EV和INCREASE试验中，分别在12周和16周时，NT-proBNP基线百分比变化的最小临床重要差异（MID）。

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.

通过在FREEDOM-EV中发生临床恶化事件或在INCREASE中6分钟步行距离的改善来评估MID达成与临床结果之间的关联。

Results

Complete data were available for 638 participants in FREEDOM-EV and 250 participants in INCREASE.

FREEDOM-EV中有638名参与者，INCREASE中有250名参与者的完整数据可用。

The median MID for NT-proBNP change in the FREEDOM-EV and INCREASE trials was a 48% improvement.

在FREEDOM-EV和INCREASE试验中，NT-proBNP变化的中位最小临床意义差异（MID）为48%的改善。

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).

在12周时达到最小临床意义差异（MID）的肺动脉高压（PAH）患者，在长期随访期间发生临床恶化事件的可能性减少了52%（风险比，0.48；95%置信区间，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.

在16周时达到最小重要差异（MID）的肺高压合并间质性肺病（PH-ILD）患者，其6分钟步行距离相对改善了40米（95%置信区间，14-66米；P = .003），与那些未达到MID的患者相比。

interpretation

Our results show the estimated MID for short-term NT-proBNP improvement in PAH and PH-ILD is remarkably similar at 48%.

我们的结果显示，在肺动脉高压（PAH）和肺高压合并间质性肺病（PH-ILD）中，短期N末端脑钠肽前体（NT-proBNP）改善的估计最小重要差异（MID）惊人地相似，为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.

在PAH和PH-ILD患者中，NT-proBNP变化达到最小临床重要差异（MID）与临床重要结果密切相关，表明在12至16周内测量NT-proBNP变化对于预后具有指导意义，并且可能对于决定是否需要对PAH和PH-ILD患者进行治疗升级的决策有帮助。