摘要：zerlasiran治疗最常见的不良事件是轻度注射部位反应，给药后第一天有2.3%-7.1%的参与者反映轻度疼痛，无治疗相关严重不良反应。新的风暴已经出现，怎么能够停滞不前？Lp(a)的恶行被陆续揭露，靶向Lp(a)的降脂药走向临床也指日可待了。参考文献：[1
原创 奇点糕 奇点网*仅供医学专业人士阅读参考最新捷报！近两年，多种降低脂蛋白(a)（Lp[a]）的药物临床试验已经进入白热化阶段。今天，又是谁带着成果上台呢？前日，两款Lp(a)降脂药的II期临床结果同时于《美国医学会杂志》期刊惊艳亮相。一款是Lp(a)的首个口服降脂药muvalaplin[1]，此次II期临床结果显示，相比于安慰剂，12周、每日一次240 mg的muvalaplin治疗可以使Lp(a)水平≥175 nmol/L、具有较高心血管事件风险的患者Lp(a)水平降低达85.8%。另一款是腹部皮下注射的小干扰 RNA（siRNA）药物zerlasiran[2]，相比于安慰剂，以450 mg、每24周两次的给药方式进行治疗36周后，zerlasiran使Lp(a)水平≥125 nmol/L、动脉粥样硬化性心血管疾病患者的Lp(a)平均水平降低85.6%，且药效持久，治疗结束半年内Lp(a)水平稳定较低。两个药物的安全性都可靠。
zerlasiran治疗最常见的不良事件是轻度注射部位反应，给药后第一天有2.3%-7.1%的参与者反映轻度疼痛，无治疗相关严重不良反应。新的风暴已经出现，怎么能够停滞不前？Lp(a)的恶行被陆续揭露，靶向Lp(a)的降脂药走向临床也指日可待了。参考文献：[1]Nicholls, S. J., Ni, W., Rhodes, G. M., Nissen, S. E., Navar, A. M., Michael, L. F., Haupt, A., & Krege, J. H. (2024). Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA, 10.1001/jama.2024.24017. Advance online publication. https://doi.org/10.1001/jama.2024.24017[2]Nissen, S. E., Wang, Q., Nicholls, S. J., Navar, A. M., Ray, K. K., Schwartz, G. G., Szarek, M., Stroes, E. S. G., Troquay, R., Dorresteijn, J. A. N., Fok, H., Rider, D. A., Romano, S., Wolski, K., & Rambaran, C. (2024). Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. JAMA, 10.1001/jama.2024.21957. Advance online publication. https://doi.org/10.1001/jama.2024.21957[3]Björnson E, Adiels M, Taskinen M-R, et al. Lipoprotein(a) is markedly more atherogenic than LDL: an apolipoprotein B-based genetic analysis. J Am Coll Cardiol. 2024;83:385-395.[4]Harpreet S. Bhatia, Simon Wandel, Peter Willeit, et al. Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol–Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis. Circulation. DOI: 10.1161/CIRCULATIONAHA.124.069556.[5]Wilson DP, Jacobson TA, Jones PH, et al. Use of lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol.2022;16:e77–e95.[6]Nissen SE, Linnebjerg H, Shen X, et al. Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial. JAMA. 2023;330(21):2075–2083. doi:10.1001/jama.2023.21835[7]O'Donoghue, M. L., Rosenson, R. S., Gencer, B., López, J. A. G., Lepor, N. E., Baum, S. J., Stout, E., Gaudet, D., Knusel, B., Kuder, J. F., Ran, X., Murphy, S. A., Wang, H., Wu, Y., Kassahun, H., Sabatine, M. S., & OCEAN(a)-DOSE Trial Investigators (2022). Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. The New England journal of medicine, 387(20), 1855–1864. https://doi.org/10.1056/NEJMoa2211023[8]Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, et al. Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med 2020;382:244-255.[9]Nicholls SJ, Nissen SE, Fleming C, et al. Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial. JAMA. 2023;330(11):1042–1053. doi:10.1001/jama.2023.16503 来源：天恒说时尚一点号
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