不同前蛋白转化酶枯草溶菌素9抑制剂在高胆固醇血症中的应用研究

Application of different preprotein converting subtilisin/kexin type 9 inhibitors in hypercholesterolemia

  • 摘要:
    目的 探讨不同前蛋白转化酶枯草溶菌素9抑制剂(PCSK9)在高胆固醇血症(FH)中的应用价值。
    方法 经倾向性匹配评分排除性别、年龄等基线资料混杂因素后, 将82例FH患者依照使用的PCSK9抑制剂分为阿利西尤组和依洛尤组, 每组41例, 且均治疗3个月。比较2组疗效, 治疗前后血脂指标甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(Apo A1)、载脂蛋白B(Apo B)、冠状动脉血流储备绝对流量储备(CFR)、相对流量储备(rCFR)、分数流量储备(FFR)、内皮功能指标血清一氧化氮(NO)、内皮素1(ET-1)、内皮舒张功能(FMD)以及不良反应。
    结果 治疗3个月后, 阿利西尤组LDL-C总达标率为97.56 %(40/41), 依洛尤组为92.68 %, 差异无统计学意义(P>0.05)。治疗后, 2组TG、TC、LDL-C、Apo B及ET-1水平均降低, HDL-C、Apo A1、CFR、rCFR、FFR及NO、FMD水平均升高, 且阿利西尤组TG、TC、LDL-C、Apo B及ET-1水平均低于依洛尤组, HDL-C、Apo A1、CFR、rCFR、FFR及NO、FMD水平均高于依洛尤组, 差异均有统计学意义(P < 0.05)。阿利西尤组不良反应发生率为12.20 %, 依洛尤组不良反应发生率为9.76 %, 差异无统计学意义(P>0.05)。
    结论 阿利西尤单抗与依洛尤单抗分别联合瑞舒伐他汀治疗FH, 均能有效改善脂代谢、冠状动脉血流储备功能及血管内皮功能, 但阿利西尤单抗效果更佳。

     

    Abstract:
    Objective To explore the application value of different preprotein converting subtilisin/kexin type 9 (PCSK9) inhibitors in familial hypercholesterolemia(FH).
    Methods 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 levelstriglyceride (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 reserveabsolute coronary flow reserve (CFR), relative coronary flow reserve (rCFR), fractional flow reserve (FFR), endothelial function indicatorsserum nitric oxide (NO), endothelin-1 (ET-1), flow mediated dilatation (FMD)and adverse reactions before and after treatment were compared between both groups.
    Results 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).
    Conclusion 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.

     

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