The relationship between mean arterial pressure and terlipressin in hepatorenal syndrome-acute kidney injury reversal: A post hoc analysis.

To further characterize the relationship between terlipressin and MAP and their impact on HRS-AKI reversal, we used patient-level data from phase 3 clinical trials REVERSE and CONFIRM.

为了进一步阐明特利加压素与平均动脉压（MAP）之间的关系以及它们对肝肾综合征-急性肾损伤（HRS-AKI）逆转的影响，我们使用了第三阶段临床试验REVERSE和CONFIRM的患者级数据。

approach_and_results

In this post hoc analysis we employed a linear mixed-effects model to assess terlipressin's impact on MAP, exploring the relationship between MAP, treatment group, and time, incorporating a random intercept for individual patients.

在这项事后分析中，我们采用线性混合效应模型来评估特利普雷辛对平均动脉压（MAP）的影响，探讨了MAP、治疗组和时间之间的关系，并为每位患者引入了随机截距。

Time-dependent Cox models analyzed MAP's role in HRS-AKI reversal. We conducted a mediation analysis to evaluate how time-weighted MAP mediated HRS-AKI reversal. This analysis included 487 patients (60% terlipressin, 40% placebo).

时间依赖的Cox模型分析了MAP在肝肾综合征-急性肾损伤（HRS-AKI）逆转中的作用。我们进行了中介分析，以评估时间加权MAP如何介导HRS-AKI的逆转。该分析包括487名患者（60%接受特利普雷辛治疗，40%接受安慰剂治疗）。

At baseline, there were no differences in median MAP between terlipressin and placebo (77 mm Hg vs. 76 mm Hg, p =0.3); the terlipressin group had significantly higher MAPs after randomization (day 1: 85 mm Hg vs. 75 mm Hg; day 3: 81 mm Hg vs. 76 mm Hg; all: p <0.001).

基线时，特利加压素组和安慰剂组的平均动脉压（MAP）中位数没有差异（77 mm Hg vs. 76 mm Hg, p =0.3）；随机化后，特利加压素组的MAP显著高于安慰剂组（第1天：85 mm Hg vs. 75 mm Hg；第3天：81 mm Hg vs. 76 mm Hg；所有：p <0.001）。

In mixed-effects models, terlipressin was associated with a 6.0 mm Hg increase in MAP over placebo occurring on day 1, with no significant interaction between the treatment group and time ( p >0.05).

在混合效应模型中，特利加压素与安慰剂相比，在第1天MAP增加了6.0 mm Hg，治疗组与时间之间没有显著的相互作用（p >0.05）。

In time-dependent Cox models, each 5 mm Hg increase in MAP was associated with 1.17× the hazard of HRS-AKI reversal (95% CI: 1.11-1.22).

在时间依赖的Cox模型中，平均动脉压（MAP）每增加5毫米汞柱，与肝肾综合征-急性肾损伤（HRS-AKI）逆转的危险比为1.17倍（95%置信区间：1.11-1.22）。

In mediation analysis, MAP significantly mediated HRS-AKI reversal, regardless of treatment group (average proportion mediated: 33%, 95% CI: 14-76).

在中介分析中，平均动脉压（MAP）显著中介了HRS-AKI的逆转，无论治疗组如何（平均中介比例：33%，95%置信区间：14-76）。

Conclusions

These data highlight that terlipressin leads to an early, sustained increase in MAP, which is a key pharmacodynamic target for HRS-AKI reversal.

这些数据强调了特利普生能够早期并持续地提高平均动脉压（MAP），这是肝肾综合征-急性肾损伤（HRS-AKI）逆转的关键药效学目标。