Banach Maciej, López-Sendon José Luis, Averna Maurizio, Cariou Bertrand, Loy Megan, Manvelian Garen, Batsu Isabela, Poulouin Yann, Gaudet Daniel
Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland.
Hospital Universitario La Paz, IdiPaz, CIBER-CV, UAM, Madrid, Spain.
Arch Med Sci. 2021 Oct 29;18(2):285-292. doi: 10.5114/aoms/143476. eCollection 2022.
The phase IIIb open-label ODYSSEY APPRISE study prospectively assessed the safety and efficacy of alirocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in a real-life setting in high cardiovascular risk patients with heterozygous familial hypercholesterolemia or low-density lipoprotein cholesterol (LDL-C) not at goal despite maximally tolerated dose statins ± other lipid-lowering therapies (NCT02476006). This post-hoc analysis assessed patient adherence to statins and alirocumab, plus alirocumab efficacy and safety, according to concomitant statin intensity and prior ezetimibe usage.
Patients received alirocumab 75 or 150 mg (dose adjustment based on physician's judgment) every 2 weeks (for ≥ 3 to ≤ 30 months).
Of 994 enrolled and treated patients, 58.4% received concomitant high-intensity statins, 18.2% received moderate/low-intensity statins, and 23.4% received no statin; 55.9% received prior ezetimibe. Mean alirocumab adherence (percent adherence defined as injections received/theoretical injections × 100) was 96.6% over 72.4 weeks' mean treatment duration. Mean LDL-C reduction from baseline at Week 12 was similar between statin intensity subgroups (53.6-55.7%). More patients achieved LDL-C < 1.8 mmol/l and/or ≥ 50% reduction from baseline in the ≥ 100% versus < 100% adherent to alirocumab subgroup; high-intensity and low/moderate-intensity subgroups versus no statin subgroup; and prior ezetimibe versus no prior ezetimibe subgroup. Treatment-emergent adverse events occurred in 65.2-75.1% and 68.0-76.3% of patients across statin and ezetimibe subgroups, respectively.
In a real-life setting, patient adherence to alirocumab was high. Alirocumab provided clinically significant reductions in LDL-C, with most patients achieving LDL-C treatment targets across background statin therapy and prior ezetimibe therapy subgroups.
IIIb期开放标签ODYSSEY APPRISE研究前瞻性评估了阿利西尤单抗（一种前蛋白转化酶枯草溶菌素/9型[PCSK9]抑制剂）在杂合子家族性高胆固醇血症或低密度脂蛋白胆固醇（LDL-C）未达目标的高心血管风险患者中的安全性和有效性，这些患者尽管接受了最大耐受剂量的他汀类药物±其他降脂治疗（NCT02476006）。这项事后分析根据他汀类药物的强度和既往依折麦布的使用情况，评估了患者对他汀类药物和阿利西尤单抗的依从性，以及阿利西尤单抗的疗效和安全性。
患者每2周接受75或150mg阿利西尤单抗（根据医生判断调整剂量）（治疗≥3至≤30个月）。
在994名登记并接受治疗的患者中，58.4%接受了高强度他汀类药物联合治疗，18.2%接受了中/低强度他汀类药物治疗，23.4%未接受他汀类药物治疗；55.9%接受过依折麦布治疗。在平均72.4周的治疗期间，阿利西尤单抗的平均依从性（依从率定义为实际注射次数/理论注射次数×100）为96.6%。在第12周时，他汀类药物强度亚组之间从基线开始的平均LDL-C降低相似（53.6 - 55.7%）。在阿利西尤单抗依从率≥100%与<100%的亚组中；高强度和低/中强度亚组与未使用他汀类药物的亚组中；以及既往使用依折麦布与未使用依折麦布的亚组中，更多患者的LDL-C<1.8mmol/L和/或较基线降低≥50%。在他汀类药物亚组和依折麦布亚组中，分别有65.2 - 75.1%和68.0 - 76.3%的患者发生治疗中出现的不良事件。
在现实生活环境中，患者对阿利西尤单抗的依从性较高。阿利西尤单抗使LDL-C有临床意义的降低，大多数患者在背景他汀类治疗和既往依折麦布治疗亚组中均达到了LDL-C治疗目标。
