Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Landelijk Expertisecentrum Familiaire Hypercholesterolemie (LEEFH), Amsterdam, The Netherlands.
J Clin Lipidol. 2018 Jul-Aug;12(4):972-980.e1. doi: 10.1016/j.jacl.2018.04.002. Epub 2018 Apr 18.
A large proportion of patients with heterozygous familial hypercholesterolemia (heFH) do not reach low-density lipoprotein cholesterol (LDL-c) levels advocated by international guidelines (<70 mg/dL or <100 mg/dL).
We set out to model which proportion of patients reach targets using conventional and novel therapies.
We performed a cross-sectional analysis in a large cohort of genetically identified heFH patients and calculated the proportion reaching treatment targets in four scenarios: (1) after 50% LDL-c reduction (representing maximal dose statin); (2) after 70% LDL-c reduction (maximal dose statin + ezetimibe); (3) additional 40% LDL-c reduction representing cholesteryl ester transfer protein inhibitor (CETPi); and (4) 60% LDL-c reduction (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9i]), on top of scenario 2. We applied 100% adherence rates and literature-based adherence rates from 62% to 80%.
We included 1,059 heFH patients with and 9,420 heFH patients without coronary heart disease (CHD). With maximal dose statin, 8.3% and 48.1% of patients with and without CHD would reach their recommended LDL-c targets, respectively. This increases to 54.3% and 93.2% when ezetimibe is added. Addition of CETPi increases these numbers to 95.7% and 99.7%, whereas adding PCSK9i would result in 99.8% and 100% goal attainment. Using literature-based adherence rates, these numbers decrease to 3.8% and 27.3% for maximal dose statin, 5.8% and 38.9% combined with ezetimibe, 31.4% and 81.2% when adding CETPi, and 40.3% and 87.1% for addition of PCSK9i.
Less than 10% with and 50% of heFH patients without CHD would reach treatment targets with maximal dose statin, but this substantially increases on addition of ezetimibe, CETPi, or PCSK9i. However, considering recently published adherence data, this might be lower in real life, especially in heFH patients with CHD.
大量杂合子家族性高胆固醇血症（heFH）患者的低密度脂蛋白胆固醇（LDL-c）水平未达到国际指南推荐的水平（<70mg/dL 或 <100mg/dL）。
我们旨在构建模型，以确定使用常规和新型疗法的患者达到治疗目标的比例。
我们对一大群经基因诊断的 heFH 患者进行了横断面分析，并在以下四种情况下计算达到治疗目标的患者比例：（1）LDL-c 降低 50%（代表最大剂量他汀类药物）；（2）LDL-c 降低 70%（最大剂量他汀类药物+依折麦布）；（3）另外降低 40%的 LDL-c，代表胆固醇酯转移蛋白抑制剂（CETPi）；（4）在方案 2 的基础上，将前蛋白转化酶枯草溶菌素/kexin 9 抑制剂（PCSK9i）降低 60%的 LDL-c。我们应用了 100%的依从率和 62%至 80%的文献报告的依从率。
我们纳入了 1059 例有冠心病（CHD）和 9420 例无 CHD 的 heFH 患者。使用最大剂量他汀类药物，分别有 8.3%和 48.1%的 CHD 患者和无 CHD 患者将达到其 LDL-c 目标值。当添加依折麦布时，这一比例分别增加到 54.3%和 93.2%。当添加 CETPi 时，这些数字增加到 95.7%和 99.7%，而添加 PCSK9i 则会使达到目标的比例分别达到 99.8%和 100%。使用文献报告的依从率，最大剂量他汀类药物的这一比例分别下降至 3.8%和 27.3%，联合使用依折麦布分别下降至 5.8%和 38.9%，添加 CETPi 分别下降至 31.4%和 81.2%，添加 PCSK9i 分别下降至 40.3%和 87.1%。
不到 10%的有 CHD 和 50%的无 CHD 的 heFH 患者使用最大剂量他汀类药物可达到治疗目标，但添加依折麦布、CETPi 或 PCSK9i 后，这一比例显著增加。然而，考虑到最近公布的依从性数据，在现实生活中，尤其是在有 CHD 的 heFH 患者中，这一比例可能会更低。
