依洛尤单抗和阿利西尤单抗的临床效果比较

朱伯达; 赵帅; 韩鹏; 王嘉仪; 曹家豪; 魏志宏; 杨庆; 杨轩; 汪钦; 王伟; 李成祥; 廉坤

doi:10.12125/j.chj.202110101

摘要:

目的观察两种前蛋白转化酶枯草杆菌蛋白酶Kexin-9抑制剂（PCSK9i）依洛尤单抗和阿利西尤单抗对动脉粥样硬化性心血管疾病（atherosclerotic cardiovascular disease，ASCVD）患者的降脂治疗有效性及安全性。

方法连续收集2019年2月～2021年7月于空军军医大学第一附属医院行经皮冠状动脉介入（percutaneous coronary intervention，PCI）术后接受PCSK9i治疗的ASCVD患者148例，依据其用药种类不同，将其分为依洛尤单抗组（n=103）和阿利西尤单抗组（n=45）。基本治疗方案是以他汀为基础联合PCSK9i的降脂方案，有20例患者予以PCSK9i单药治疗。记录两组患者住院期间的基线资料（年龄、性别、BMI、血压、心率、谷丙转氨酶、谷草转氨酶、肌酐、左心室射血分数(left ventricular ejection fraction，LVEF)、学历、住院时间、既往病史及术后用药情况），并且用药2（中位数）月后复查血脂水平，观察患者血脂降幅及药物不良反应发生情况。

结果相较于阿利西尤单抗组，依洛尤单抗组患者舒张压（P<0.05）和谷草转氨酶（P<0.01）水平更低，且LVEF（P<0.05）水平较低，术后服用阿司匹林（P<0.05）和ACEI/ARB（P<0.05）的比例更高。用药后两组患者TC和LDL-C水平均显著降低，且均具有统计学意义（P<0.01），但依洛尤单抗组患者HDL-C水平升高较为显著（P<0.05）。同时，治疗后阿利西尤单抗组较依洛尤单抗组的LDL-C水平更低（P<0.01）。依洛尤单抗组和阿利西尤单抗组患者LDL-C<1.4 mmol/L的达标率分别为65.3％ vs. 84.2％；LDL-C<1.8 mmol/L的达标率为80.0% vs. 94.1％。在术后不良反应方面，两组均无不良反应发生，两种药物对谷丙转氨酶、谷草转氨酶、尿酸、肌酐水平的影响无统计学差异。

结论两组药物均可显著降低总胆固醇和低密度脂蛋白胆固醇水平，且二者的安全性均较为良好但在降脂达标率方面阿利西尤单抗略优于依洛尤单抗。

Abstract:

AIM To observe the effects of evolocumab and alirocumab --- two inhibitors of the preprotein converting enzyme, Bacillus subtilis protease Kexin-9 (PCSK9) --- on the efficacy and safety of lipid-lowering therapy in patients with atherosclerotic cardiovascular disease (ASCVD).

METHODS A total of 148 ASCVD patients who received PCSK9i after percutaneous coronary intervention (PCI) in Xijing Hospital of Air Force Military Medical University from February 2019 to July 2021 were consecutively collected. They were divided into evolocumab group (n=103) and alirocumab group (n=45). The primary treatment regimen was statin based lipid-lowering regimen combined with PCSK9i, and 20 patients received PCSK9i monotherapy. Baseline data during hospitalization (age, sex, BMI, blood pressure, heart rate, alanine aminotransferase, aspartate aminotransferase, creatinine, LVEF, education background, length of stay, past medical history and postoperative medication) were recorded 48h before surgery in the 2 groups. Blood lipid levels were reviewed after 2 months of medication, and the decrease of blood lipid and the occurrence of adverse drug reactions were observed.

RESULTS Compared with the alirocumab group, patients in the evolocumab group had lower diastolic blood pressure (P<0.05) and aspartate aminotransferase (P<0.01) levels, lower LVEF (P<0.05) levels, and a higher proportion of patients taking aspirin (P<0.05) and ACEI/ARB (P<0.05) after surgery. After treatment, TC and LDL-C levels in 2 groups were significantly decreased, with statistical significance (P<0.01), but HDL-C level in eluzumab group was significantly increased (P<0.05). At the same time, the LDL-C level of the alirocumab group was lower than that of the evolocumab group after treatment (P<0.01). In evolocumab group and alirocumab group, the compliance rate of LDL-C<1.4 mmol/L was 65.3% vs. 84.2% and the standard rate of LDL-C<1.8 mmol/L was 80.0% vs. 94.1%. In terms of postoperative adverse reactions, no adverse reactions occurred in the two groups, and there was no statistical difference in the effects of the two drugs on liver and kidney functions.

CONCLUSION Both evolocumab and alirocumab have good effect in reducing total cholesterol and low density lipoprotein , and the safety of them are good.Alirocumab is slightly better than evolocumab in lipid lowering rate.

依洛尤单抗和阿利西尤单抗的临床效果比较

Comparison of clinical effect between evolocumab and alirocumab