Citation: | ZHAO Delong, ZHOU Haiyan, YUE Fengjuan, LI Wei. Application of different preprotein converting subtilisin/kexin type 9 inhibitors in hypercholesterolemia[J]. Journal of Clinical Medicine in Practice, 2024, 28(9): 29-33, 39. DOI: 10.7619/jcmp.20234278 |
To explore the application value of different preprotein converting subtilisin/kexin type 9 (PCSK9) inhibitors in familial hypercholesterolemia(FH).
Patients with FH in our hospital were selected and divided into alirocumab group and evolocumab group according to the different PCSK9 inhibitors after excluding the confounding factors of baseline data such as gender and age by propensity score matching, 41 patients in each group were matched. Both groups were treated for 3 months. The therapeutic effect, and blood lipids levels[triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) index, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B)], coronary flow reserve[absolute coronary flow reserve (CFR), relative coronary flow reserve (rCFR), fractional flow reserve (FFR)], endothelial function indicators[serum nitric oxide (NO), endothelin-1 (ET-1), flow mediated dilatation (FMD)]and adverse reactions before and after treatment were compared between both groups.
After three months of treatment, the overall standardized rate of LDL-C in the alirocumab group was 97.56 % (40/41), and 92.68 % in the evolocumab group, but there was no statistically significant difference between the two groups (P>0.05). After treatment, the levels of TG, TC, LDL-C, Apo B, and ET-1 in both groups decreased, while the levels of HDL-C, Apo A1, CFR, rCFR, FFR, NO, and FMD increased. Additionally, the levels of TG, TC, LDL-C, Apo B, and ET-1 in the alirocumab group were lower than those in the evolocumab group, while the levels of HDL-C, Apo A1, CFR, rCFR, FFR, NO, and FMD were higher, and the differences were statistically significant (P < 0.05). The incidence of adverse reactions was 12.20 % in the alirocumab group and 9.76 % in the evolocumab group, with no statistically significant difference (P>0.05).
Alirocumab or evolocumab combined with rosuvastatin in treating FH can effectively improve the lipid metabolism, coronary flow reserve function and vascular endothelial function in the treatment of patients with hypercholesterolemia, but alirocumab has a better effect.
[1] |
蒋琬姿, 张丽雯, 贺彩红, 等. 家族性高胆固醇血症研究进展[J]. 遗传, 2021, 43(11): 1011-1040. https://www.cnki.com.cn/Article/CJFDTOTAL-YCZZ202111001.htm
|
[2] |
母光妍, 刘志艳, 张涵煦, 等. 新型高胆固醇血症治疗药物的研究现状[J]. 中国临床药理学杂志, 2021, 37(15): 2092-2095. https://www.cnki.com.cn/Article/CJFDTOTAL-GLYZ202115037.htm
|
[3] |
王小冬, 杜艳萍, 肖峰, 等. 阿托伐他汀对老年高胆固醇血症合并低骨量患者骨量和肌力的作用效果研究[J]. 中国全科医学, 2020, 23(21): 2669-2672. doi: 10.12114/j.issn.1007-9572.2020.00.102
|
[4] |
赵紫楠, 张亚同, 李可欣, 等. PCSK9抑制剂治疗高胆固醇血症有效性与安全性的Meta分析[J]. 中国循证医学杂志, 2020, 20(11): 1284-1294. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXZ202011008.htm
|
[5] |
中华医学会心血管病学分会动脉粥样硬化及冠心病学组, 中华心血管病杂志编辑委员会. 家族性高胆固醇血症筛查与诊治中国专家共识[J]. 临床医学研究与实践, 2018, 3(9): 201. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS201809098.htm
|
[6] |
ZHENG T, MOU X N, ZHANG J, et al. Clinical effect and changes of ET-1, FMD and NO levels in the treatment of acute cerebral infarction with acanthopanax injection[J]. Am J Transl Res, 2021, 13(4): 3600-3608.
|
[7] |
高扬, 王贇霞, 高传玉. ≤ 45岁急性冠脉综合征患者可能家族性高胆固醇血症的临床特点及血脂达标影响因素研究[J]. 中国全科医学, 2023, 26(18): 2232-2237. doi: 10.12114/j.issn.1007-9572.2022.0780
|
[8] |
王依繁, 张翼, 林阳. 他汀类药物联合依折麦布用于冠心病患者治疗的有效性和安全性评价[J]. 中国医院药学杂志, 2022, 42(5): 538-543. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYZ202205014.htm
|
[9] |
张虎, 刘艳梅, 杨振. 瑞舒伐他汀与阿托伐他汀治疗冠心病伴高脂血症患者的临床疗效及安全性[J]. 重庆医学, 2022, 51(S02): 280-282. https://www.cnki.com.cn/Article/CJFDTOTAL-DKYY202107005.htm
|
[10] |
金子妍, 罗敏, 田燕, 等. PCSK9抑制剂治疗家族性高胆固醇血症有效性与安全性的系统评价[J]. 中国医院药学杂志, 2021, 41(8): 833-839. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYZ202108014.htm
|
[11] |
张瑶, 杨晋静, 刘静祎, 等. PCSK9在动脉粥样硬化性心血管疾病作用机制中的研究进展[J]. 中国医师杂志, 2023, 25(8): 1260-1264. doi: 10.3760/cma.j.cn431274-20221125-01230
|
[12] |
王同, 王丰云, 宿东升, 等. 早期应用PCSK-9抑制剂对急性ST段抬高型心肌梗死罪犯血管自发再通患者的疗效分析[J]. 实用临床医药杂志, 2021, 25(11): 77-81. doi: 10.7619/jcmp.20211019
|
[13] |
朱伯达, 赵帅, 韩鹏, 等. 依洛尤单抗和阿利西尤单抗的临床效果比较[J]. 心脏杂志, 2022, 34(3): 293-298. https://www.cnki.com.cn/Article/CJFDTOTAL-XGNZ202203010.htm
|
[14] |
张莉莉, 韩雅玲, 马蕊, 等. 依洛尤单抗短期快速调脂在高危急性冠状动脉综合征患者中应用价值[J]. 临床军医杂志, 2019, 47(10): 1081-1083. https://www.cnki.com.cn/Article/CJFDTOTAL-JYGZ201910023.htm
|
[15] |
叶韬华, 王慧勇, 柏慧, 等. 阿利西尤单抗联用他汀类药物对急性冠脉综合征患者血脂水平的影响[J]. 中国医药科学, 2021, 11(10): 1-6. https://www.cnki.com.cn/Article/CJFDTOTAL-GYKX202110063.htm
|
[16] |
CYBULSKA B, KŁOSIEWICZ-LATOSZEK L, PENSON P E, et al. How much should LDL cholesterol be lowered in secondary prevention Clinical efficacy and safety in the era of PCSK9 inhibitors[J]. Prog Cardiovasc Dis, 2021, 67: 65-74. doi: 10.1016/j.pcad.2020.12.008
|
[17] |
李慧芳, 袁天杰, 江曙. 基于肠道微生物的口服药物生物利用度研究进展[J]. 中国医药工业杂志, 2022, 53(9): 1262-1269. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHOU202209005.htm
|
[18] |
BRANDL F, BUSSLINGER S, ZANGEMEISTER-WITTKE U, et al. Optimizing the anti-tumor efficacy of protein-drug conjugates by engineering the molecular size and half-life[J]. J Control Release, 2020, 327: 186-197. doi: 10.1016/j.jconrel.2020.08.004
|
[19] |
王志明. 转基因小鼠技术在全人源抗体药物研发中的应用[J]. 中国新药杂志, 2016, 25(22): 2596-2602. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ201622013.htm
|
[20] |
吕若芸, 陈忱, 魏敬双. 治疗性抗体药物开发中IgG亚型选择[J]. 中国生物工程杂志, 2016, 36(7): 104-111. https://www.cnki.com.cn/Article/CJFDTOTAL-SWGJ201607014.htm
|
[21] |
李江帆, 胡晔, 庞宏贤, 等. 基于OpenFDA对依洛尤单抗及阿利西尤单抗不良反应的比较分析[J]. 中国药物警戒, 2021, 18(10): 965-968. https://www.cnki.com.cn/Article/CJFDTOTAL-YWJJ202110015.htm
|
[22] |
CHEN L, CHEN Q, ZHONG J X, et al. Effect of low-density lipoprotein cholesterol goal achievement on vascular physiology evaluated by quantitative flow ratio in patients who underwent percutaneous coronary intervention[J]. Front Cardiovasc Med, 2021, 8: 679599.
|
[23] |
TOYA T, CORBAN M T, PARK J Y, et al. Prognostic impact and clinical outcomes of coronary flow reserve and hyperaemic microvascular resistance[J]. EuroIntervention, 2021, 17(7): 569-575.
|
[24] |
林智海, 王正东, 李平, 等. PCSK9抑制剂-依洛尤单抗对急性冠状动脉综合征患者血脂谱及血管内皮功能的影响[J]. 河北医学, 2021, 27(3): 508-512. https://www.cnki.com.cn/Article/CJFDTOTAL-HCYX202103033.htm
|
[25] |
RØNNOW SAND N P, NISSEN L, WINTHER S, et al. Prediction of coronary revascularization in stable angina: comparison of FFRCT with CMR stress perfusion imaging[J]. JACC Cardiovasc Imaging, 2020, 13(4): 994-1004.
|
[26] |
周晓婧, 提拉柯孜·图尔荪, 冯伟, 等. 冠状动脉CT血流储备分数在冠状动脉临界狭窄患者心肌缺血诊断中的应用[J]. 山东医药, 2023, 63(27): 43-46. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYY202327008.htm
|
[27] |
高霏, 马晓腾, 王志坚, 等. 他汀类药物联合阿利西尤单抗对血脂不达标的冠心病患者冠状动脉斑块结构和稳定性的影响[J]. 中国医药, 2021, 16(11): 1618-1621. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYG202111005.htm
|
[28] |
史红, 姚启恒, 宋现涛, 等. PCSK9抑制剂在临床应用中需要关注的问题[J]. 中华心血管病杂志: 网络版, 2021, 4(1): 1-7.
|