作者：吕洋，柳燕，李宏伟，臧洁，宋金东

单位：

1.266500山东省青岛市黄岛区中医医院神经内科 2.266500山东省青岛市黄岛区人民医院神经内科 3.250014山东省济南市，山东第一医科大学生物医学科学学院 省医药生物技术研究中心 通信作者：宋金东，E-mail：223111467@qq.com

Units：

1.Department of Neurology, Traditional Chinese Medical Hospital of Huangdao District, Qingdao 266500, China 2.Department of Neurology, People's Hospital of Huangdao District, Qingdao 266500, China 3.Shandong First Medical University Biomedical Science College/Shandong Medicinal & Biotechnology, Jinan 250014, China

关键词：

缺血性卒中; 阿替普酶; 替罗非班; 静脉溶栓;

Keywords：

Ischemic stroke; Alteplase; Tirofiban; Intravenous thrombolysis

CLC：

DOI：

10.12114/j.issn.1008-5971.2022.00.321

Funds：

青岛市2020年度医药科研项目（2020-WJZD241）

摘要：

目的 探讨阿替普酶静脉溶栓后早期联合替罗非班治疗轻中度急性缺血性卒中（AIS）及各TOAST亚型的效果。方法 选取2020—2021年青岛市黄岛区中医医院神经内科收治的轻中度AIS患者300例，按照随机数字表法将其分为常规组和替罗非班组，每组150例。按照TOAST分型将两组患者进一步分别分为小动脉闭塞型（SAO）、大动脉粥样硬化型（LAA）、心源性栓塞型（CE）、其他已知原因型+不明原因型（其他）亚组，其中常规SAO亚组70例、常规LAA亚组45例、常规CE亚组30例、常规其他亚组5例，替罗非班SAO亚组60例、替罗非班LAA亚组51例、替罗非班CE亚组33例、替罗非班其他亚组6例。常规组在阿替普酶静脉溶栓治疗基础上予以常规治疗。替罗非班组在常规治疗的基础上，于阿替普酶静脉溶栓后2 h联合替罗非班治疗。比较常规组与替罗非班组及各常规亚组与替罗非班亚组入院时、治疗7 d后美国国立卫生研究院卒中量表（NIHSS）和治疗90 d后改良Rankin量表（mRS）评分、预后、安全性指标[颅内出血（IH）、症状性颅内出血（sICH）发生率及死亡率]。结果 常规组与替罗非班组治疗7 d后NIHSS评分分别低于本组入院时，且替罗非班组低于常规组（P<0.05）；替罗非班组治疗90 d后mRS评分低于常规组，预后良好者占比高于常规组（P<0.05）。常规SAO亚组与替罗非班SAO亚组治疗7 d后NIHSS评分分别低于本组入院时，且替罗非班SAO亚组低于常规SAO亚组（P<0.05）；替罗非班SAO亚组治疗90 d后mRS评分低于常规SAO亚组，预后良好者占比高于常规SAO亚组（P<0.05）。常规LAA亚组与替罗非班LAA亚组入院时、治疗7 d后NIHSS评分及治疗90 d后mRS评分、预后良好者占比比较，差异无统计学意义（P>0.05）；常规LAA亚组、替罗非班LAA亚组治疗7 d后NIHSS评分分别低于本组入院时（P<0.05）。常规CE亚组与替罗非班CE亚组入院时、治疗7 d后NIHSS评分及治疗90 d后mRS评分、预后良好者占比比较，差异无统计学意义（P>0.05）；常规CE亚组、替罗非班CE亚组治疗7 d后NIHSS评分分别低于本组入院时（P<0.05）。常规组与替罗非班组IH发生率、sICH发生率、死亡率比较，差异无统计学意义（P>0.05）。常规SAO亚组有1例发生IH，无sICH、死亡发生；替罗非班SAO亚组无IH、sICH、死亡发生。常规LAA亚组与替罗非班LAA亚组IH发生率、sICH发生率、死亡率比较，差异无统计学意义（P>0.05）。常规CE亚组与替罗非班CE亚组IH发生率、sICH发生率、死亡率比较，差异无统计学意义（P>0.05）。结论 阿替普酶静脉溶栓后早期联合替罗非班治疗轻中度AIS患者安全有效，尤其对于SAO患者，建议在阿替普酶静脉溶栓后2 h联合替罗非班以降低致死率、改善患者预后。

Abstract：

【Abstract】　Objective To investigate the effect of early combination of tirofiban after intravenous thrombolysis with alteplase in the treatment of mild to moderate acute ischemic stroke (AIS) and TOAST subtypes. Methods A total of 300 patients with mild to moderate AIS admitted to Department of Neurology of Traditional Chinese Medical Hospital of Huangdao District from 2020 to 2021 were selected and divided into routine group and tirofiban group according to the random number table method, with 150 cases in each group. Patients in the two groups were further divided into small artery occlusion (SAO) , large artery atherosclerosis (LAA) , cardiac embolism (CE) and other known cause + unknown cause (others) subgroup according to TOAST type, including 70 cases in conventional SAO subgroup, 45 cases in conventional LAA subgroup, 30 cases in conventional CE subgroup, 5 cases in conventional other subgroup, 60 cases in tirofiban SAO subgroup, 51 cases in tirofiban LAA subgroup, 33 cases in tirofiban CE subgroup, and 6 cases in tirofiban other subgroup. On the basis of intravenous thrombolytic therapy with alteplase, conventional group was given routine treatment. On the basis of routine treatment, tirofiban group was treated with tirofiban at 2 h after intravenous thrombolysis therapy with alteplase. The National Institutes of Health Stroke Scale (NIHSS) score at admission and 7 days after treatment and Modified Rankin Scale (mRS) score 90 days after treatment, prognosis and safety indexes [incidence of intracranial hemorrhage (IH) and symptomatic intracranial hemorrhage (sICH) and mortality] were compared between conventional group and tirofiban group, and between conventional subgroups and tirofiban subgroups. Results NIHSS score after 7 days of treatment of conventional group and tirofiban group was lower than that at admission respectively, and that of tirofiban group was lower than that of conventional group (P < 0.05) . After 90 days of treatment, mRS score of tirofiban group was lower than that of conventional group, and the proportion of patients with good prognosis was higher than that of conventional group ( P < 0.05) . NIHSS scores after 7 days of treatment in conventional SAO subgroup and tirofiban SAO subgroup were lower than those at admission respectively, and those of tirofiban SAO subgroup were lower than those of conventional SAO subgroup (P < 0.05) . The mRS score after 90 days of treatment of tirofiban SAO subgroup was lower than that of conventional SAO subgroup, and the proportion of patients with good prognosis was higher than that of conventional SAO subgroup (P < 0.05) . There were no significant differences in NIHSS score at admission and 7 days after treatment, mRS score 90 days after treatment, and the proportion of patients with good prognosis between conventional LAA subgroup and tirofiban LAA subgroup (P > 0.05) . NIHSS scores after 7 days of treatment of conventional LAA subgroup and tirofiban LAA subgroup were lower than those at admission respectively (P < 0.05) . There were no significant differences in the NIHSS score at admission and after 7 days of treatment, mRS score after 90 days of treatment, and the proportion of patients with good prognosis between conventional CE subgroup and tirofiban CE subgroup (P > 0.05) . NIHSS score after 7 days of treatment of conventional CE subgroup and tirofiban CE subgroup was lower than that at admission respectively (P < 0.05) . There were no significant differences in the incidence of IH, sICH and mortality between conventional group and tirofiban group (P > 0.05) . One case of IH occurred in conventional SAO subgroup, but no sICH or death occurred. No IH, sICH and death occurred in tirofiban SAO subgroup. There were no significant differences in the incidence of IH, sICH and mortality between conventional LAA subgroup and tirofiban LAA subgroup (P > 0.05) . There was no significant difference in the incidence of IH, sICH and mortality between conventional CE subgroup and tirofiban CE subgroup (P > 0.05) . Conclusion Early combination of tirofiban after intravenous thrombolysis with alteplase is safe and effective in the treatment of mild to moderate AIS, especially for SAO patients, it is recommended to combine tirofiban at 2 h after intravenous thrombolytic therapy with alteplase to reduce the mortality and improve the prognosis of patients.

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