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首页|期刊导航|中国脑血管病杂志|低剂量替罗非班用于急性颅内破裂动脉瘤支架置入结合弹簧圈栓塞治疗的有效性和安全性分析

低剂量替罗非班用于急性颅内破裂动脉瘤支架置入结合弹簧圈栓塞治疗的有效性和安全性分析OA北大核心CSTPCD

Efficacy and safety of low-dose tirofiban infusion used in stent-assisted coiling for ruptured intracranial aneurysms

中文摘要英文摘要

目的 探讨低剂量替罗非班用于支架置入结合弹簧圈栓塞治疗急性颅内破裂动脉瘤的有效性和安全性.方法 回顾性连续纳入2011年4月至2020年9月常州市第一人民医院神经外科收治的颅内动脉瘤破裂伴蛛网膜下腔出血并于入院24~48h内行支架置入结合弹簧圈栓塞且使用抗血小板聚集药物治疗患者335例,根据抗血小板聚集药物治疗方案的不同,将患者分为双抗组(89例)和替罗非班组(246例).收集所有患者的基线及临床资料并进行组间比较,包括年龄、性别、高血压病、糖尿病、入院Hunt-Hess分级、入院改良Fisher量表评分、动脉瘤直径(>5 mm、≤5 mm)、动脉瘤位置(前循环、后循环)及术后急性脑积水或脑室积血、术后即刻动脉瘤栓塞情况.所有患者颅内动脉瘤破裂伴蛛网膜下腔出血均为入院后急诊头部CT平扫确认.术后即刻采用Raymond分级标准评估栓塞效果:Ⅰ级指完全不显影(完全栓塞),Ⅱ级指仅瘤颈显影(不完全栓塞),Ⅲ级指瘤体显影,其中Raymond分级Ⅰ~Ⅱ级为有效栓塞.替罗非班组:在动脉瘤瘤腔内填入弹簧圈后、支架释放时,给予4.2 μg/kg替罗非班静脉注射后以0.07 μg/(kg·min)静脉滴注维持6~8h,并在停止静脉滴注2 h前予序贯阿司匹林100 mg与氯吡格雷75 mg双联抗血小板聚集药物治疗.双抗组:至少于支架置入前2 h给予顿服负荷剂量阿司匹林300 mg+氯吡格雷300 mg,术后第2天给予阿司匹林100 mg+氯吡格雷75 mg.所有患者均接受术后持续口服6个月阿司匹林(100mg/d)和术后持续口服3个月氯吡格雷(75mg/d)治疗.观察并比较两组有效性指标、安全性指标、不良事件及其他并发症发生情况,其中有效性指标为术中及术后72 h内血栓事件发生率,安全性指标为术中及术后早期(术后48 h以内)颅内出血事件发生率、术后晚期(术后48 h及以后)颅内出血事件发生率和脑室外引流相关颅内出血事件(症状性、无症状性)发生率,不良事件为药物相关血小板减少症发生情况,其他并发症指延迟性脑缺血事件发生情况.采用改良Rankin量表(mRS)评分评估患者术后180d临床预后,将mRS评分≤2分定义为预后良好,mRS评分>2分为预后不良,其中6分为死亡.结果 (1)替罗非班组与双抗组的基线及临床资料的组间差异均无统计学意义(均P>0.05)o(2)替罗非班组与双抗组术后180 d良好预后[75.2%(185/246)比74.2%(66/89),P=0.845]及死亡[10.2%(25/246)比 12.4%(11/89),P=0.566]患者比例差异均无统计学意义.(3)抗血小板聚集方案有效性比较结果显示,替罗非班组与双抗组术中[0.8%(2/246)比 4.5%(4/89),P=0.075]、术后 72 h 血栓事件[11.0%(27/246)比 13.5%(12/89),P=0.527]发生比例差异均无统计学意义.(4)抗血小板聚集方案安全性比较结果显示,替罗非班组术后早期颅内出血事件发生率低于双抗组[2.8%(7/246)比10.1%(9/89),P=0.014],接受脑室外引流术发生症状性脑室外引流相关颅内出血事件患者比例组间差异无统计学意义(0比2/15,P=0.050).两组术中颅内出血事件(1.6%比3.4%,P=0.580)、术后晚期颅内出血事件(3.3%比4.5%,P=0.836)、药物相关血小板减少症(0.4%比1.1%,P=0.461)发生比例差异均无统计学意义.结论 低剂量替罗非班方案用于支架置入结合弹簧圈栓塞治疗颅内急性破裂动脉瘤在预防血栓事件方面与双抗效果类似,且不增加早期出血事件发生率.

Objective To explore the efficacy and safety of low-dose tirofiban in stent-assisted coil embolization(SAC)for ruptured intracranial aneurysms.Methods From April 2011 to September 2020,335 patients of ruptured intracranial aneurysms with subarachnoid hemorrhage(SAH)admitted in the First People's Hospital of Changzhou were retrospectively analyzed.All cases underwent stent-assisted coil embolization within 24-48 h and antiplatelet medications.The patients were divided into dual antibody group(89 cases)and tirofiban group(246 cases).Baseline and clinical data of all patients were collected for comparison between groups,including age,sex,hypertension,diabetes mellitus,Hunt-Hess grade at admission,modified Fisher scale score at admission,aneurysm diameter(>5 mm,≤5 mm),aneurysm location(anterior circulation,posterior circulation),postoperative acute hydrocephalus or intraventricular hemorrhage,postoperative complete embolization rate of ruptured aneurysm.All patients with ruptured intracranial aneurysm with SAH were confirmed by emergency cerebral CT scan after admission.The Raymond grading criteria were used to evaluate the embolization effect after operation:grade Ⅰ refers to no development(complete embolization),grade Ⅱ refers to only aneurysm neck development(incomplete embolization),and grade Ⅲ refers to aneurysm body development,in which Raymond grading Ⅰ orⅡ indicates effective embolization.Tirofiban group:4.2 μg/kg tirofiban was intravenously injected after the coil was placed in the aneurysm lumen and the stent was released,followed by maintenance dose 0.07 μg/(kg·min)for 6-8 h,and aspirin 100 mg and clopidogrel 75 mg were given as sequential dual antiplatelet therapy 2 hours before the tirofiban infusion was stopped.Dual antiplatelet group:a loading dose of aspirin 300 mg and clopidogrel 300 mg was given at least 2 hours before stent implantation,and then transferred to aspirin 100 mg and clopidogrel 75 mg given on the second day after operation.All patients received aspirin(100mg/d)for 6 months and clopidogrel(75 mg/d)for 3 months after operation.The efficacy indicators,safety indicators,adverse events and other complications of the two groups were collected and compared.The efficacy indicators were the incidence of thrombotic events during operation and within 72 hours after operation.The safety indicators were the incidence of intraoperative and early postoperative intracranial hemorrhage(within 48 hours after operation),the incidence of late postoperative intracranial hemorrhage(over 48 hours after operation),and the incidence of intracranial hemorrhage related to external ventricular drainage(symptomatic and asymptomatic).The adverse event was the occurrence of drug-related thrombocytopenia.Other complications were delayed ischemic events.The modified Rankin scale(mRS)score was used to evaluate the clinical prognosis of patients at 180 days after operation.mRS score ≤2 was defined as good prognosis,mRS score>2 was defined as poor prognosis,of which 6 was defined as death.Results(1)There were no significant differences in baseline and clinical data between the tirofiban group and the dual antibody group(all P>0.05).(2)There was no significant difference in the proportion of patients with good outcome(75.2%[185/246]vs.74.2%[66/89],P=0.845)and death(10.2%[25/246]vs.12.4%[11/89],P=0.566)at 180 days after operation between the tirofiban group and the dual antiplatelet group.(3)There was no significant difference in the incidence of intraoperative(0.8%[2/246]vs.4.5%[4/89],P=0.075)and postoperative thrombotic events(11.0%[27/246]vs.13.5%[12/89],P=0.527)between the tirofiban group and the dual antiplatelet group.(4)Results about safety comparison between this two antiplatelet regimens showed that the incidence of early postoperative intracranial hemorrhage were lower in the tirofiban group than that in the dual antiplatelet group(2.8%[7/246]vs.10.1%[9/89],P=0.014).There were no significant differences in the symptomatic external ventricular drainage related intracranial hemorrhage(0 vs.2/15,P=0.050),incidences of intraoperative intracranial hemorrhage(1.6%vs.3.4%,P=0.580),late postoperative intracranial hemorrhage(3.3%vs.4.5%,P=0.836),and drug-related thrombocytopenia(0.4%vs.1.1%,P=0.461)between the two groups.Conclusion Low-dose tirofiban infusion in SAC for ruptured aneurysms may prevent perioperative thromboembolic events without high risk of intracranial hemorrhage.

莫仡;曹洁;朱旭成;陈荣华;邵华明;宣井岗;彭亚

213000 江苏省常州市第一人民医院神经外科

破裂颅内动脉瘤蛛网膜下腔出血替罗非班低剂量支架结合弹簧圈栓塞术

Ruptured intracranial aneurysmSubarachnoid hemorrhageTirofibanLow-doseStent-assisted coil embolization

《中国脑血管病杂志》 2024 (009)

587-594 / 8

常州市第十六批科技计划(应用基础研究)项目(CJ20200111)

10.3969/j.issn.1672-5921.2024.09.002

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