载脂蛋白 B 代谢紊乱患者的前蛋白转化酶枯草溶菌素 9 抑制剂治疗：真实世界处方。

Proprotein convertase subtilisin/kexin type 9 inhibitors treatment in dyslipidemic patients: a real world prescription.

机构信息

Department of Internal Medicine and Therapeutics.

Laboratory of Molecular Medicine, University of Pavia, Pavia.

出版信息

J Cardiovasc Med (Hagerstown). 2022 Feb 1;23(2):91-97. doi: 10.2459/JCM.0000000000001237.

DOI:10.2459/JCM.0000000000001237

PMID:34690259

Abstract

AIM

Dyslipidemia is recognized as one of the major risk factors for cardiovascular diseases. This retrospective observational study was aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dyslipidemic patients with a lipid profile not well controlled by maximally tolerated statin therapy or intolerant to these lipid-lowering drugs. We enrolled 151 patients, of whom, 119 were taking evolocumab and 32 alirocumab.

RESULTS

Total cholesterol significantly decreased progressively until the fourth year; after 4 years there was a significant reduction (-125.5 mg/dl, -51.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -2.8 mg/dl (-2.3%) compared with the third year. Low-density lipoprotein-cholesterol (LDL-C) also decreased significantly until the fourth year. After 3 years, there was a significant reduction (-117.8 mg/dl, -71.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year) and -13.9 mg/dl (-22.8%) compared with the second year; after 4 years there was a significant reduction (-121.4 mg/dl, -73.7%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -3.6 mg/dl (-7.7%) compared with the third year. High-density lipoprotein-cholesterol increased significantly only during the fourth year of detection. After 3 years, there was a nonsignificant increase (4.9 mg/dl, 10.0%, P = 0.061 vs baseline) and 1.6 mg/dl (3.1%) compared with the second year; after 4 years, there was a significant increase (5.2 mg/dl, 10.6%, P < 0.05 vs baseline) and 0.3 mg/dl (0.6%) compared with the third year. The value of Tg was significantly reduced progressively until the second year and then stabilized in the third and fourth years. After 3 years, the value of Tg stabilized (-48.6 mg/dl, -32.4%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) and -4.8 mg/dl (-4.5%) compared with the second year; after 4 years (-46.4 mg/dl, -31.0%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) there was a slight and nonsignificant increase of 2.2 mg/dl (2.2%) compared with the third year. Regarding adverse events, both drugs were well tolerated.

CONCLUSIONS

We showed that PCSK9 inhibitors are well tolerated and provide long-term significant LDL-C lowering in individuals with hyperlipidemia.

摘要

目的

血脂异常被认为是心血管疾病的主要危险因素之一。本回顾性观察性研究旨在评估前蛋白转化酶枯草溶菌素/糜蛋白酶 9（PCSK9）抑制剂在最大耐受剂量他汀类药物治疗血脂控制不佳或不耐受这些降脂药物的血脂异常患者中的疗效。我们共纳入 151 例患者，其中 119 例接受依洛尤单抗治疗，32 例接受阿利西尤单抗治疗。

结果

总胆固醇水平持续显著降低，直至第 4 年；第 4 年后，与基线相比，总胆固醇水平显著降低（-125.5mg/dl，-51.5%，P<0.0001，与第 1 年相比，P<0.05，与第 2 年相比，P<0.05），与第 3 年相比，总胆固醇水平降低了 2.8mg/dl（-2.3%）。低密度脂蛋白胆固醇（LDL-C）也显著降低，直至第 4 年。第 3 年后，与基线相比，LDL-C 水平显著降低（-117.8mg/dl，-71.5%，P<0.0001，与第 1 年相比，P<0.05，与第 2 年相比，P<0.05），与第 2 年相比，LDL-C 水平降低了 13.9mg/dl（-22.8%）；第 4 年后，与基线相比，LDL-C 水平显著降低（-121.4mg/dl，-73.7%，P<0.0001，与第 1 年相比，P<0.05，与第 2 年相比，P<0.05），与第 3 年相比，LDL-C 水平降低了 3.6mg/dl（-7.7%）。高密度脂蛋白胆固醇仅在检测的第 4 年显著增加。第 3 年后，与基线相比，高密度脂蛋白胆固醇水平升高（4.9mg/dl，10.0%，P=0.061），升高了 1.6mg/dl（3.1%），与第 2 年相比；第 4 年后，与基线相比，高密度脂蛋白胆固醇水平显著升高（5.2mg/dl，10.6%，P<0.05），升高了 0.3mg/dl（0.6%），与第 3 年相比。甘油三酯的水平持续显著降低，直至第 2 年，然后在第 3 年和第 4 年稳定。第 3 年后，甘油三酯水平稳定（-48.6mg/dl，-32.4%，P<0.01，与基线相比，与第 1 年相比，P<0.05），与第 2 年相比，甘油三酯水平降低了 4.8mg/dl（-4.5%）；第 4 年与基线相比（-46.4mg/dl，-31.0%，P<0.01，与第 1 年相比，P<0.05），甘油三酯水平略有升高，为 2.2mg/dl（2.2%），与第 3 年相比。关于不良事件，两种药物均耐受良好。