The Department of Cardiology, Lady Davis Carmel Medical Center, Haifa, Israel; The Faculty of Medicine, Technion, Israel Institute of Medicine, Haifa, Israel.
The Faculty of Medicine, Technion, Israel Institute of Medicine, Haifa, Israel.
J Clin Lipidol. 2021 Jan-Feb;15(1):202-211.e2. doi: 10.1016/j.jacl.2020.11.004. Epub 2020 Nov 13.
Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein cholesterol (LDL-C), improving cardiovascular outcomes in clinical trials when added to statin therapy.
As real-world evidence is lacking, we aimed to evaluate treatment and adherence patterns using PCSK9i in clinical practice.
We investigated 1600 patients initiating PCSK9i between January 2016 and December 2019 in a large health maintenance organization. Treatment discontinuation was defined as a gap ≥60 days between last days' supply of one prescription and the start of the next. Re-initiation rates as well as proportion of days covered (PDC) over 1-year period and attainment of lipid goals under PCSK9i, were analyzed.
Evolocumab 140 mg was initiated by 50.7%, alirocumab 75 mg by 29.5% and 150 mg by 19.8%. Cumulative discontinuation rates were 28.1% after 6-months and 49.9% after 3-years. Overall, 58% of the patients that discontinued therapy have re-initiated PCSK9i (31% after 3-months from discontinuation). Mean PDC over 1-year of therapy was 56% ± 29, with PDC ≥80% evident in 29%. Of those with established cardiovascular disease (n = 991), 55% achieved LDL-C<70 mg/dL and 38% LDL-C<55 mg/dL. Attainment rates were lower in patients with PDC<80%, baseline LDL-C>190 mg/dL and in those not treated with concurrent statin therapy.
In real-world practice of patients treated by PCSK9i, high proportion of early treatment discontinuation was evident, with non-negligible re-initiation rates but overall low medication coverage over time. This have contributed to sub-optimal attainment of LDL-C treatment goals, particularly observed in patients with severe hypercholesterolemia, inadequate drug adherence, and those using PCSK9i as monotherapy.
前蛋白转化酶枯草溶菌素 9 抑制剂（PCSK9i）在他汀类药物治疗的基础上，可有效降低低密度脂蛋白胆固醇（LDL-C），改善临床试验中的心血管结局。
鉴于目前缺乏真实世界的数据，我们旨在评估临床实践中使用 PCSK9i 的治疗和依从模式。
我们调查了一家大型健康维护组织中，2016 年 1 月至 2019 年 12 月期间 1600 例起始 PCSK9i 治疗的患者。定义治疗中断为上次处方最后一天与下次开始之间的间隔≥60 天。分析了 1 年内的再起始率、覆盖率（PDC）以及 PCSK9i 治疗下达到血脂目标的比例。
起始应用 140mg 依洛尤单抗、75mg 阿利西尤单抗和 150mg 阿利西尤单抗的患者分别占 50.7%、29.5%和 19.8%。6 个月后累计停药率为 28.1%，3 年后为 49.9%。总体而言，58%停药的患者重新开始 PCSK9i 治疗（3 个月后 31%重新开始）。1 年治疗期间的平均 PDC 为 56%±29%，PDC≥80%的比例为 29%。在 991 例有明确心血管疾病的患者中，55%达到 LDL-C<70mg/dL，38%达到 LDL-C<55mg/dL。PDC<80%、基线 LDL-C>190mg/dL和未同时接受他汀类药物治疗的患者达标率较低。
在 PCSK9i 治疗患者的真实世界实践中，早期治疗中断的比例较高，再起始率相当高，但总体上随着时间的推移药物覆盖率较低。这导致 LDL-C 治疗目标的达标率不理想，尤其是在严重高胆固醇血症、药物依从性不足的患者以及将 PCSK9i 作为单药治疗的患者中更为明显。
