Background

Familial hypercholesterolemia (FH) is characterized by increased cardiovascular risk; despite-high intensity statins, only few patients with FH achieve the recommended low-density lipoprotein cholesterol (LDL-C) targets.

Objective

We aimed to evaluate the effectiveness of six-month add-on therapy with proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) or ezetimibe on lipid profile and pulse wave velocity (PWV) in patients with FH.

Methods

In this observational study, we evaluated 98 genetically confirmed patients with FH with an LDL-C off-target despite high-intensity statins with or without ezetimibe; of these, 53 patients (statin plus ezetimibe) added PCSK9-i (PCSK9-i group) and 45 (statin only) added ezetimibe (EZE group) per applicable guidelines and reimbursement rules. All patients obtained biochemical analysis and PWV evaluation at baseline and after six months of optimized treatment.

Results

After 6 months of add-on therapy, most patients achieving LDL-C targets were in the PCSK9-i group (77.3% PCSK9-i group vs 37.8% EZE group, P < .001). The PCSK9-i group achieved both a greater LDL-C and PWV reduction than the EZE group [−51% vs −22.8%, P < .001 and −15% vs −8.5%, P < .01, respectively]. In a linear regression analysis, we showed a coefficient (r) of 0.334 for the relationship between ΔPWV and ΔLDL (P < .05); moreover, in an exploratory analysis, the relationship appeared to be stronger in patients with FH without cardiovascular events (r = 0.422, P < .01).

Conclusions

Lipid and PWV profiles in patients with FH significantly improved after addition of PCSK9-i or ezetimibe to high-intensity statin therapy; moreover, ΔPWV was associated with ΔLDL. Our results are consistent with a beneficial role of these novel therapies in FH subjects.

中文翻译：

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在家族性高胆固醇血症患者中，在高强度他汀类药物中加入PCSK9抑制剂或依泽替米贝后，动脉僵硬度得到改善：两脂中心的真实经验。

背景

家族性高胆固醇血症（FH）的特征是心血管风险增加；尽管他汀类药物强度很高，但只有少数FH患者达到推荐的低密度脂蛋白胆固醇（LDL-C）目标。

目的

我们旨在评估前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型抑制剂（PCSK9-i）或依折麦布六个月补充治疗对FH患者血脂和脉搏波速度（PWV）的有效性。

方法

在这项观察性研究中，我们评估了98例经遗传学证实的FH患者，尽管其高强度他汀类药物存在或不存在依泽替米贝，但LDL-C脱靶。其中，根据适用指南和报销规则，有53例患者（他汀类药物和依泽替米贝）加用PCSK9-i（PCSK9-i组），有45例患者（仅他汀类药物）加用依泽替米贝（EZE组）。所有患者均在基线和优化治疗六个月后获得了生化分析和PWV评估。

结果

附加治疗6个月后，大多数达到LDL-C指标的患者在PCSK9-i组（PCSK9-i组为77.3％，EZE组为37.8％，P  <.001）。与EZE组相比，PCSK9-i组的LDL-C和PWV降低均更大[分别为-51％对-22.8％，P  <.001和-15％对-8.5％，P  <.01]。在线性回归分析中，我们显示出ΔPWV和ΔLDL之间的关系的系数（r）为0.334（P  <.05）；此外，在一项探索性分析中，这种关系在没有心血管事件的FH患者中似乎更强（r = 0.422，P  <.01）。

结论

在高强度他汀类药物治疗中加入PCSK9-i或ezetimibe后，FH患者的血脂和PWV谱显着改善；另外，ΔPWV与ΔLDL相关。我们的结果与这些新疗法在FH受试者中的有益作用一致。