摘要目的:观察前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂联合瑞舒伐他汀对急性缺血性脑卒中患者血脂水平和短期预后的影响，探讨有效和安全的治疗方案，为临床提供依据。方法:连续纳入2022年4月至2023年3月于徐州市中心医院收治的发病72 h内急性脑梗死、血脂≥2.6 mmol/L的患者为研究对象，采用随机数字表法按治疗方案将患者分成A组（瑞舒伐他汀20 mg，1次/d）、B组（瑞舒伐他汀10 mg，1次/d+阿利西尤单抗75 mg，1次/2周）和C组（瑞舒伐他汀20 mg，1次/d+阿利西尤单抗75 mg，1次/2周）3组，收集3组患者的一般基线资料、90 d美国国立卫生研究院卒中量表评分、改良Rankin量表评分、不良事件及严重不良事件发生等情况。主要疗效结局为90 d时低密度脂蛋白胆固醇（LDL-C）较基线的降低程度，次要疗效结局为90 d内脑卒中复发例数、复发率及复发时间等。主要安全性结局为90 d内肝功能不全（转氨酶升高≥正常值3倍），次要安全性结局为90 d内脑卒中引起的死亡、致死及非致死性心肌梗死。结果:共纳入501例患者，A组166例、B组167例、C组168例，3组基线资料差异均无统计学意义（均 P>0.05）。A、B、C 3组90 d 时LDL-C较基线降低，差值分别为-1.5（-1.7，-1.4）mmol/L、-2.2（-2.5，-2.1）mmol/L、-2.2（-2.6，-2.1）mmol/L，3组间差异有统计学意义（ H=1.497， P<0.001）；A组分别与B组、C组患者相比，差异均有统计学意义（ Z=-11.125， P=0.006； Z=-9.475， P=0.012），而B组与C组患者相比差异无统计学意义（ Z=1.650， P=0.946）。A、B、C 3组患者90 d内脑卒中复发例数（复发率）分别为12例（7.2%）、4例（2.4%）、5例（3.0%），3组间差异无统计学意义（χ 2=5.773， P>0.05）；3组复发时间分别为（43.0±7.4）d、（66.0±8.3）d、（62.2±5.6）d，3组间差异有统计学意义（ F=14.096， P=0.001）。与A组相比，B组和C组患者90 d内脑卒中复发时间延长（ Z=-3.108， P=0.002； Z=-2.871， P=0.004），而B组与C组患者90 d内脑卒中复发时间差异无统计学意义（ Z=0.397， P=0.692）。90 d内脑卒中复发时间与90 d时 LDL-C水平呈正相关（ β=0.850， P=0.031）。A组出现肝功能不全患者10例（6.0%）、B组1例（0.6%）、C组9例（5.4%），3组间差异有统计学意义（χ 2=7.622， P=0.022）；B组与C组相比差异有统计学意义（ P=0.011）。次要安全性结局90 d内脑卒中引起的死亡［A组1例（0.6%），B组0例（0），C组1例（0.6%）］、致死及非致死性心肌梗死［A组3例（1.8%），B组1例（0.6%），C组1例（0.6%）］，3组间差异均无统计学意义（均 P>0.05）。 结论:急性缺血性脑卒中患者应用PCSK9抑制剂联合瑞舒伐他汀（无论是中、高剂量）使LDL-C水平较基线显著降低，同时可延长卒中复发时间，减少肝功能不全等不良反应，安全性高，其中PCSK9抑制剂联合中剂量瑞舒伐他汀效果更佳。

abstractsObjective:To observe the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor combined with rosuvastatin on lipid levels and short-term prognosis in patients with acute ischemic stroke, and to explore the optimal therapeutic regimen in terms of efficacy and safety, so as to provide a basis for clinical practice.Methods:Consecutive patients with acute cerebral infarction within 72 hours of onset and lipids≥2.6 mmol/L admitted to Xuzhou Central Hospital from April 2022 to March 2023 were included in the study, and the randomized numeric table method was used to divide them into 3 groups of different treatment regimens, group A (rosuvastatin 20 mg, once a day), group B (rosuvastatin 10 mg, once a day+alirocumab 75 mg, once 2 weeks) and group C (rosuvastatin 20 mg, once a day+alirocumab 75 mg, once 2 weeks). General baseline data, National Institutes of Health Stroke Scale score, modified Rankin Scale score on day 90 and the occurrence of adverse events and serious adverse events were collected from the 3 groups. The primary efficacy outcome was the degree of reduction in low density lipoprotein-cholesterol (LDL-C) from baseline on day 90. The secondary efficacy outcomes were recurrence rate and time to recurrence in stroke patients within 90 days,etc. The primary safety outcome was hepatic insufficiency (transaminase elevation≥3 times normal) within 90 days. The secondary safety outcomes were death due to stroke within 90 days and fatal and nonfatal myocardial infarction.Results:A total of 501 patients were included, 166 patients in group A, 167 patients in group B, and 168 patients in group C. The differences in the baseline data of the 3 groups were not statistically significant (all P>0.05). LDL-C was reduced from baseline on day 90 in groups A, B, and C, with the differences of -1.5 (-1.7, -1.4) mmol/L, -2.2 (-2.5, -2.1) mmol/L and -2.2 (-2.6, -2.1) mmol/L, respectively, with statistically significant differences among the 3 groups ( H=1.497, P<0.001); the differences between the group A and group B, and between the group A and group C, were statistically significant ( Z=-11.125, P=0.006; Z=-9.475, P=0.012), while the difference between the group B and group C was not statistically significant ( Z=1.650, P=0.946). The numbers of 90-day stroke recurrence cases (recurrence rate) in patients in the groups A, B, and C were 12 (7.2%), 4 (2.4%), and 5 (3.0%), respectively, without statistically significant difference among the 3 groups ( χ 2=5.773, P>0.05); the recurrence time of patients in the groups A, B and C was (43.0±7.4) d, (66.0±8.3) d and (62.2±5.6) d, respectively, and the differences among the 3 groups were statistically significant ( F=14.096, P=0.001). Compared with the group A, patients in the groups B and C had a prolonged time to stroke recurrence within 90 days ( Z=-3.108, P=0.002; Z=-2.871, P=0.004), whereas the difference in the time to stroke recurrence within 90 days between patients in the groups B and C was not statistically significant ( Z=0.397, P=0.692). The time to stroke recurrence within 90 days was positively correlated with the level of LDL-C on day 90 ( β=0.850, P=0.031). Ten patients (6.0%) in the group A developed hepatic insufficiency, 1 patient (0.6%) in the group B, and 9 patients (5.4%) in the group C. The differences among the 3 groups were statistically significant (χ 2=7.622, P=0.022); and the difference between the group B and group C was statistically significant ( P=0.011). The differences of secondary safety endpoints, death due to stroke within 90 days [1 case (0.6%) in the group A, 0 case (0) in the group B, and 1 case (0.6%) in the group C], fatal and nonfatal myocardial infarction within 90 days [3 cases (1.8%) in the group A, 1 case (0.6%) in the group B, and 1 case (0.6%) in the group C], were not statistically significant among the 3 groups (all P>0.05). Conclusions:In patients with acute ischemic stroke, PCSK9 inhibitor combined with rosuvastatin (both medium and high doses) significantly reduced LDL-C levels compared with baseline, and at the same time prolonged the time to stroke recurrence, reduced adverse effects such as hepatic insufficiency, and had a high degree of safety. PCSK9 inhibitor combined with medium-dose rosuvastatin had a better effect.