Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized trial.

However, 35%-45% of patients still have insufficient HVPG decrease.

然而，35%-45%的患者 HVPG 降低仍然不足。

Statins ameliorate endothelial dysfunction, reduce hepatic vascular resistance, and have pleiotropic effects.

他汀类药物能够改善内皮功能障碍，降低肝脏血管阻力，并具有多种效应。

We investigated whether the addition of simvastatin improves the efficacy of carvedilol on HVPG in cirrhosis with severe portal hypertension and suboptimal response to traditional NSBBs.

我们研究了在对传统非选择性β受体阻滞剂反应不佳的严重门静脉高压肝硬化患者中，辛伐他汀的添加是否能提高卡维地洛对肝静脉压力梯度(HVPG)的疗效。

Methods

Patients with cirrhosis and high-risk varices referred for primary prophylaxis were consecutively included.

被转诊进行初级预防的肝硬化和高危静脉曲张患者被连续纳入研究。

HVPG was measured at baseline and again after i.v. propranolol.

基线时测量HVPG，静脉注射普萘洛尔后再测量一次。

Suboptimal responders (HVPG decrease <20%) were treated with carvedilol and were randomized to double-blindadministration of placebo or simvastatin.

反应不足的患者（HVPG降低<20%）接受了卡维地洛治疗，并被随机分配接受安慰剂或辛伐他汀的双盲给药。

Chronic HVPG response was assessed after 4-6 weeks, repeating HVPG measurements after a standard liquid meal to estimate endothelial dysfunction.

在4-6周后评估慢性HVPG反应，通过标准液体餐后重复HVPG测量来估计内皮功能障碍。

Plasma samples were obtained before each study to investigate inflammatory parameters.

在研究开始前获取了血浆样本，以研究炎症参数。

Results

Of 184 eligible patients, 82 were randomized to carvedilol + simvastatin (N = 41) or carvedilol + placebo (N = 41).

在184名符合条件的患者中，有82名被随机分配到卡维地洛+辛伐他汀（N=41）或卡维地洛+安慰剂（N=41）。

Baseline characteristics were similar.

基线特征相似。

HVPG significantly decreased with both, carvedilol + simvastatin (18.6 ± 4 to 15.7 ± 4 mm Hg, p < 0.001) and carvedilol + placebo (18.9 ± 3 to 16.9 ± 3 mm Hg, p < 0.001).

HVPG（肝静脉压力梯度）在卡维地洛+辛伐他汀（从18.6 ± 4降至15.7 ± 4毫米汞柱，p < 0.001）和卡维地洛+安慰剂（从18.9 ± 3降至16.9 ± 3毫米汞柱，p < 0.001）治疗后显著下降。

The decrease was greater with carvedilol + simvastatin (2.97 ± 2.5 vs. 2.05 ± 1.6 mm Hg, p = 0.031).

与单独使用相比，卡维地洛加辛伐他汀联合使用时血压下降更为显著（2.97 ± 2.5 vs. 2.05 ± 1.6 毫米汞柱，p = 0.031）。

An HVPG decrease ≥20% occurred in 37% versus 15% of patients, respectively (OR: 3.37, 95% CI = 1.15-9.85; p = 0.021).

分别有37%和15%的患者出现HVPG降低≥20%（比值比：3.37，95%置信区间=1.15-9.85；p = 0.021）。

With test meal, HVPG increased in both groups ( p < 0.01), although carvedilol + simvastatin attenuated such increment (12 ± 8% vs. 23 ± 16%, p < 0.001).

在测试餐后，两组的HVPG均有所增加（p < 0.01），但卡维地洛+辛伐他汀减轻了这种增加（12 ± 8% vs. 23 ± 16%，p < 0.001）。

Cytokine levels (Interleukine-6, monocyte-chemoattractant protein-1, and malondialdehyde) decreased significantly more with carvedilol + simvastatin ( p < 0.01).

细胞因子水平（白细胞介素-6、单核细胞趋化蛋白-1和丙二醛）在卡维地洛+辛伐他汀治疗下显著降低（p < 0.01）。

The incidenceof adverse events was similar.

不良事件的发生率相似。

Conclusions

In patients with severe portal hypertension (all with high-risk varices) and suboptimal hemodynamic response to traditional NSBBs, combined therapy with carvedilol plus simvastatin significantly enhances the portal pressure reduction achieved with carvedilol monotherapy, improves endothelial dysfunction, and reduces proinflammatory cytokines.

在患有严重门静脉高压（所有患者均有高风险的静脉曲张）且对传统非选择性β受体阻滞剂（NSBBs）血流动力学反应不佳的患者中，联合使用卡维地洛和辛伐他汀治疗显著增强了卡维地洛单药治疗所达到的门静脉压力降低效果，改善了内皮功能障碍，并减少了促炎细胞因子。