Cardiac Allograft Vasculopathy Inhibition With Alirocumab: The CAVIAR Trial.

Dyslipidemia is a major contributor to the development of cardiac allograft vasculopathy.

血脂异常是心脏移植物血管病变发展的一个主要因素。

The safety and effectiveness of proprotein convertase subtilisin/kexin 9 inhibition to lower cholesterol and to prevent cardiac allograft vasculopathy early after HT are not well established.

前蛋白转化酶枯草溶菌素/kexin 9抑制剂降低胆固醇和预防心脏移植后早期血管病变的安全性和有效性尚未得到充分确立。

Methods

In this investigator-initiated, prospective, multicenter, double-blindrandomized trial, participants were randomized early after HT to receive either alirocumab or placebo in addition to rosuvastatin.

在这项由研究者发起的前瞻性、多中心、双盲随机试验中，参与者在心脏移植后早期被随机分配接受alirocumab或安慰剂，以及瑞舒伐他汀的治疗。

Before randomization and at 1 year, all participants underwent invasive coronary assessment, including angiography, fractional flow reserve, coronary flow reserve, the index of microcirculatory resistance, and intravascular ultrasound with near-infrared spectroscopy.

随机分组前和1年后，所有参与者均接受了侵入性冠状动脉评估，包括血管造影、分数流量储备、冠状动脉储备、微循环阻力指数以及近红外光谱联合血管内超声检查。

Lipid values were assessed at baseline and at prespecified intervals.

基线时以及预先设定的时间间隔评估了脂质值。

The primary end point was the change in coronary artery plaque volume from baseline to 1 year after HT based on serial intravascular ultrasound.

主要终点是基于连续血管内超声评估的冠状动脉斑块体积从基线到心脏移植后1年的变化。

Results

A total of 114 HT recipients were included (57 assigned to alirocumab and 57 assigned to placebo).

共有114名心脏移植受者被纳入研究（57名被分配到alirocumab组，57名被分配到安慰剂组）。

Baseline characteristics were well matched between the 2 groups.

两组的基线特征匹配良好。

The low-density lipoprotein cholesterol levels decreased significantly from baseline to 1 year in the alirocumab arm (72.7±31.7 to 31.5±20.7 mg/dL; P<0.001) and did not change with placebo (69.0±22.4 to 69.2±28.1 mg/dL; P=0.92).

在alirocumab组中，低密度脂蛋白胆固醇水平从基线到1年显著下降（从72.7±31.7降至31.5±20.7 mg/dL；P<0.001），而安慰剂组则没有变化（从69.0±22.4升至69.2±28.1 mg/dL；P=0.92）。

Plaque volume increased numerically in both groups from baseline to 12 months (alirocumab, 176.3±95.2 to 184.5±105.4 mm³; P=0.23; placebo 173.7±96.7 to 183.1±109.8 mm3; P=0.15).

从基线到12个月，两组的斑块体积数值上都有所增加（阿利罗单抗组从176.3±95.2增加到184.5±105.4 mm³；P=0.23；安慰剂组从173.7±96.7增加到183.1±109.8 mm³；P=0.15）。

The change in plaque volume (mean difference in differences) did not differ between groups (1.01 [0.89-1.14]; P=0.86).

两组间斑块体积的变化（差异的平均差异）没有差异（1.01 [0.89-1.14]；P=0.86）。

Fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance did not change significantly with the addition of alirocumab.

加入alirocumab后，分数血流储备、冠状动脉血流储备和微循环阻力指数没有显著变化。

There were no significant adverse events related to alirocumab.

与alirocumab相关的不良事件没有显著性。

Conclusions

Proprotein convertase subtilisin/kexin 9 inhibition with alirocumab in addition to statin therapy early after HT safely lowers low-density lipoprotein cholesterol but did not reduce coronary artery plaque progression after 1 year compared with rosuvastatin alone in patients with a low baseline low-density lipoprotein cholesterol.

在心脏移植后早期，使用阿利库单抗抑制前蛋白转化酶枯草溶菌素/角蛋白酶9，与他汀类药物联合治疗安全地降低了低密度脂蛋白胆固醇，但在基线低密度脂蛋白胆固醇较低的患者中，与单独使用瑞舒伐他汀相比，未能在1年后减少冠状动脉斑块进展。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537742.

网址：https://www.clinicaltrials.gov; 唯一标识符：NCT03537742。