摘要
目的分析急性缺血性卒中合并非瓣膜性心房颤动(NVAF)患者出院时口服抗凝药物使用情况及其影响因素。方法连续回顾性纳入急性缺血性卒中合并心房颤动患者登记研究(NCT04080830)中2016年1月至2020年12月首都医科大学宣武医院神经内科收治的急性缺血性卒中合并NVAF的住院患者702例,CHA 2DS 2-VASc评分[NVAF卒中风险评分:C为充血性心力衰竭,H为高血压,A 2为年龄≥75岁计2分,D为糖尿病,S 2为卒中或短暂性脑缺血发作计2分,V为血管性疾病,A为年龄65~74岁,Sc为性别(女性)]≥2分,收集患者的一般情况(性别、年龄、体质量指数)、既往史[下肢血管狭窄或闭塞、急性期下肢静脉血栓或肺栓塞、心功能不全、脑梗死和(或)短暂性脑缺血发作、肝病史和(或)肝功能异常]、心脑血管疾病危险因素(冠心病、高血压病、高脂血症、糖尿病、吸烟、饮酒)、相关实验室检查(血红蛋白≤90 g/L、血肌酐≥200μmol/L等)、量表评分[NVAF卒中风险评分、出血风险评分、美国国立卫生研究院卒中量表(NIHSS)评分、改良Rankin量表(mRS)评分]、出院时抗栓药物使用情况以及有无大面积脑梗死、梗死后出血转化、共存颅内外血管狭窄、急性期非主要出血、急性期大出血、医疗保险报销范围等。依据年份分层,即2016、2017、2018、2019、2020年,对各年份急性缺血性卒中合并NVAF患者出院时抗栓药物使用占比及趋势进行比较。根据新型口服抗凝药(NOACs)纳入医疗保险系统分为医保前(2016—2017年)组与医保后(2018—2020年)组,对相关数据进行对比分析。分析急性缺血性卒中合并NVAF患者出院时抗凝药物使用情况及其变化趋势,并分析NOCAs进入医疗保险系统后,对影响出院时口服抗凝药物使用情况的相关因素。比较不同抗凝药物出血事件发生率。医疗保险范围包括农村合作医疗报销、城镇医疗保险报销和职工医疗保险报销。抗栓治疗包括抗凝及抗血小板聚集治疗。CHA 2DS 2-VASc评分≥2分者均首选抗凝治疗,包括口服华法林、NOACs及低分子肝素;对于应首选抗凝治疗,但因年龄>80岁、出血风险高的患者,经与其沟通表示拒绝抗凝治疗或对抗凝药物过敏者则给予抗血小板聚集治疗,包括口服阿司匹林肠溶片、硫酸氢氯吡格雷片。经沟通拒绝抗栓治疗、对抗栓药物过敏、出院时仍有症状性出血转化、致命性出血等以上症状之一者,不予抗栓治疗。结果(1)2016、2017、2018、2019、2020年抗栓药物治疗使用占比分别为66.1%(74/112)、75.3%(113/150)、84.9%(107/126)、83.9%(161/192)、77.9%(95/122),不同年份急性缺血性卒中合并NVAF患者出院时抗栓药物使用占比的差异有统计学意义(χ^(2)=29.83,P<0.05)。抗凝药物的使用率大幅度上升,从2016年22.3%(25/112)至2018年50.0%(63/126),之后趋于平稳;无抗栓药物使用占比呈下降趋势;抗血小板聚集药物的使用趋于平稳状态。(2)2016、2017、2018、2019、2020年抗凝药物使用占比分别为22.3%(25/112)、40.7%(61/150)、50.0%(63/126)、47.9%(92/192)、44.3%(54/122),5年间不同抗凝药物的使用的变化趋势有统计学意义(χ^(2)=66.87,P<0.05),2016年至2018年NOACs呈大幅上升,从2016年的36.0%(9/25)至2018年的88.9%(56/63),之后趋于平稳;低分子肝素及华法林的使用呈大幅下降,2018年后均处于平稳状态。(3)2018年NOACS进入医疗保险,对比医疗保险前后抗栓占比差异有统计学意义(χ^(2)=18.37,P<0.01),抗凝药物从32.8%(86/262)提高到47.5%(209/440);抗凝药物种类占比亦有统计学意义(χ^(2)=62.90,P<0.01),NOACS在由39.5%(34/86)提高到83.3%(174/209)。(4)多因素Logistic回归分析结果显示,年龄≥75岁(OR=2.315,P<0.01)、共存颅内外血管狭窄(OR=1.674,P=0.016)、大面积梗死比例(OR=1.914,P=0.014)、梗死后出血转化(OR=3.374,P<0.01)和急性期非主要出血(OR=2.872,P=0.020)是出院时使用抗凝药物的独立影响因素。3种抗凝药物应用后的出血事件发生率均较低,且差异无统计学意义(P>0.05)。结论自2018年NOACs进入医疗保险后,NOACs的应用可以明显提高急性缺血性卒中合并NVAF患者出院时的抗凝药物使用率及NOACs在抗凝药物中的占比。高龄、共存颅内外血管狭窄、大面积梗死比例、梗死后出血转化及急性期非主要出血是不利于出院时抗凝药物使用的主要因素,加强出院患者随访是将来提升急性缺血性卒中合并NVAF患者的二级预防管理的重要因素。
Objective To analyze the trend of anticoagulation usage and influencing factors in acute ischemic stroke(AIS)patients with nonvalvular atrial fibrillation patients(NVAF).Methods A total of 702 AIS patients with NVAF admitted to the Department of Neurology of Xuanwu Hospital,Capital Medical University from January 2016 to December 2020 were enrolled retrospectively in the registration study of acute ischemic stroke with atrial fibrillation(NCT04080830).Patients had CHA_(2)DS_(2)-VASc(NVAF stroke risk score:C for congestive heart failure,H for hypertension,A_(2) for age≥75 years old as 2 points,D for diabetes,S_(2) for stroke or transient ischemic attack as 2 points,V for vascular disease,A for age 65-74 years old,Sc for gender[female])≥2 points.Patient′s general condition(gender,age,body mass index),past medical history(lower limb vascular stenosis or occlusion,acute lower extremity venous thrombosis or pulmonary embolism,cardiac insufficiency,cerebral infarction and[or]transient ischemic attack,history of liver disease and[or]abnormal liver function),risk factors for cardiovascular disease(coronary heart disease,hypertension,hyperlipidemia,diabetes,smoking and drinking),relevant laboratory tests(hemoglobin≤90 g/L,serum creatinine≥200μmol/L,etc.),scale scores(NVAF stroke risk score,bleeding risk score,the National Institutes of Health Stroke Scale[NIHSS]score,modified Rankin scale[mRS]score),the use of antithrombotic drugs at discharge,large cerebral infarction,post-infarction hemorrhagic transformation,co-existing intracranial and extracranial vascular stenosis,non-major acute hemorrhage,acute massive hemorrhage,reimbursement scope of medical insurance,etc.The proportion and trend of antithrombotic drug use at discharge in AIS patients with NVAF were compared according to year stratification,i.e.,2016,2017,2018,2019 and 2020.According to the inclusion time of new oral anticoagulants(NOACs)into the medical insurance system,they were divided into pre-medical insurance group(2016—2017)and post-medical insurance group(2018—2020),and relevant data were compared and analyzed.The use and trend of anticoagulants at discharge in AIS patients with NVAF,and related factors affecting the use of oral anticoagulants at discharge after NOCAs entered the medical insurance system were analyzed.Incidence of bleeding events with different anticoagulants were compared.Medical insurance includes reimbursement of rural cooperative medical insurance,urban medical insurance and employee medical insurance.Antithrombotic therapy includes anticoagulant and antiplatelet aggregation therapy.Patients with CHA_(2)DS_(2)-VASc score≥2 preferred anticoagulant therapy,including oral warfarin,NOACs and low-molecular-weight heparin.For patients who should use anticoagulant therapy as the first choice but with age>80 years old,at high risk of bleeding,refuse anticoagulant therapy after communication or are allergic to anticoagulant drugs,antiplatelet aggregation therapy was given,including oral Aspirin enteric-coated tablets and clopidogrel hydrogen sulfate.Antithrombotic therapy shall not be given to those who refuse antithrombotic therapy after communication,are allergic to antithrombotic drugs,and still have symptomatic bleeding transformation or fatal bleeding upon discharge.Results(1)In 2016,2017,2018,2019 and 2020,the proportion of antithrombotic drug therapy use was 66.1%(74/112),75.3%(113/150),84.9%(107/126),83.9%(161/192)and 77.9%(95/122),respectively.There was significant difference in the proportion of antithrombotic drugs use at discharge in AIS patients with NVAF in different years(χ^(2)=29.83,P<0.05).The use rate of anticoagulants increased significantly from 22.3%(25/112)in 2016 to 50.0%(63/126)in 2018,and then stabilized.The proportion of patients without antithrombotic state decreased significantly.The use of antiplatelet drugs tended to be stable.(2)The proportions of anticoagulant use in 2016,2017,2018,2019 and 2020 were 22.3%(25/112),40.7%(61/150),50.0%(63/126),47.9%(92/192)and 44.3%(54/122),respectively.There was statistical significance in the use of different anticoagulants over the 5-year period(χ^(2)=66.87,P<0.05).The use of NOACs increased significantly from 36.0%(9/25)in 2016 to 88.9%(56/63)in 2018,and then stabilized.The use of low-molecular-weight heparin and warfarin decreased significantly and remained stable after 2018.(3)In 2018,with NOACs entering the medical insurance,the proportion of antithrombotic drugs before and after medical insurance was statistically significant(χ^(2)=18.37,P<0.01),and anticoagulant drugs increased from 32.8%(86/262)to 47.5%(209/440);the proportion of anticoagulant drugs was also statistically significant(χ^(2)=62.90,P<0.01);NOACs increased from 39.5%(34/86)to 83.3%(174/209).(4)Multivariate Logistic regression analysis showed age≥75 years old(OR=2.315,P<0.01),co-existing intracranial and extracranial vascular stenosis(OR=1.674,P=0.016),proportion of large area infarction(OR=1.914,P=0.014),post-infarction hemorrhagic transformation(OR=3.374,P<0.01)and acute non-major bleeding(OR=2.872,P=0.020)were independent factors affecting the use of anticoagulant drugs at discharge;the incidence of bleeding events of the three anticoagulant drugs was low,and there was no significant difference among them(P>0.05).Conclusions Since the introduction of NOACs into medical insurance in 2018,the application of NOACs can significantly increase the rate of anticoagulants use and the proportion of NOACs in anticoagulants at discharge in AIS patients with NVAF.Advanced age,co-existing intracranial and extracranial vascular stenosis,proportion of large area infarction,post-infarction hemorrhagic transformation and acute non-major bleeding were the main factors influencing anticoagulation use at discharge.Strengthening follow-up of discharged patients are important factors to improve secondary prevention management of AIS patients with NVAF in the future.
作者
邱雪
薛素芳
宋海庆
QiuXue;Xue Sufang;Song Haiqing(Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)
出处
《中国脑血管病杂志》
CAS
CSCD
北大核心
2021年第11期753-764,共12页
Chinese Journal of Cerebrovascular Diseases
基金
国家重点研发计划重大慢性非传染性疾病防控研究重点专项(2016YFC1300600)
首都卫生发展科研专项(首发2020-2-2014)。
关键词
急性缺血性卒中
心房颤动
抗凝治疗
Acute ischemic stroke
Atrial fibrillation
Anticoagulant therapy
作者简介
通信作者:宋海庆,Email:songhq@xwhosp.org。
