Increased tissue plasminogen activator levels in patients with nonvalvular atrial fibrillation

OBJECTIVE: To determine whether plasma tissue plasminogen activator (tPA) levels (a) are higher in patients with novalvular atrial fibrillation (NVAF) than in control subjects in sinus rhythm; (b) differ between NVAF patients with and without a history of an embolic event (transient ischemic attack or embolic stroke); and (c) differ in control subjects with and without a history of thrombotic stroke. DESIGN: Cross-sectional study. SETTING: Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals. PATIENTS: Seventy-four NVAF patients (24 with and 50 without a history of an embolic event), separated into 3 groups: no prior embolic event and no warfarin use (group 1), no prior embolic event and warfarin use (group 2), and prior embolic event and warfarin use (group 3). Forty control subjects in sinus rhythm (29 without and 11 with prior thrombotic stroke). OUTCOME MEASURES: Plasma tPA levels. RESULTS: The age-adjusted mean tPA levels exceeded the upper limit of normal in all 3 NVAF groups but not in the control groups. The NVAF patients had significantly higher mean tPA levels than the control subjects (p = 0.015). The levels did not differ significantly between the NVAF patients with a history of an embolic event and those without such a history. The control subjects with a history of thrombotic stroke had significantly higher mean tPA levels than the other control subjects (p = 0.03). CONCLUSIONS: NVAF patients, regardless of their history of embolic events, and control patients with a history of thrombotic stroke have higher tPA levels than subjects in sinus rhythm without a history of stroke. A prospective, longitudinal study involving NVAF patients is required to determine whether high baseline tPA levels are associated with, and perhaps causally related to, an increased risk of stroke.     

单中心1 000例房颤患者的抗凝现状横断面调查

 目的  调查房颤患者的流行病学资料和抗凝治疗现状,为提高房颤患者的抗凝效率提供资料。方法  调查华山医院门诊及病房1 000例房颤患者的病史、一般情况、合并疾病、辅助检查和治疗方案,按照脑卒中史学、脑卒中风险评分及CHA2DS2-VASc评分情况进行分层分析,了解房颤患者临床特征和抗凝现状。结果  1 000例房颤患者平均年龄(72.1±11.1)岁,合并疾病前3位为高血压病(65%)、冠心病(32%)和糖尿病(27%)。非瓣膜性房颤(non-valvular atrial fibrillation,NVAF)患者占6%。22%的房颤患者有脑卒中史,根据脑卒中与否分组,脑卒中组年龄更大、房颤病程更长、高血压控制更差。所有患者总体抗凝比32%,抗血小板比46%。脑卒中组抗凝比例44%,高于非脑卒中组 (P<0.001)。但78%房颤患者在经历脑卒中后才开始抗凝。NVAF患者CHA2DS2-VASc评分为2~5分时,抗凝比例随分值增加而增加。2~6分时患者抗血小板比例增高,7~8分时,抗凝和抗血小板比例都减少。结论  目前房颤患者抗凝比例低,抗凝主要集中于房颤合并脑卒中患者。抗凝治疗减少脑卒中的发生,脑卒中后的抗凝仍可获益。但脑卒中前抗凝意义更大。     

低强度华法林抗凝治疗脑卒中风险房颤患者的临床研究

目的应用CHADS2卒中危险评分和HEMORR2HAGES出血风险评分,观察低强度华法林抗凝治疗高卒中风险、高出血风险房颤患者的抗栓疗效和安全性。方法选择CHADS2卒中危险评分3～6分、HEMORR2HAGES评分≥2分的房颤患者60例,随机分成两组：每组各30例,组Ⅰ为低强度华法林治疗组[1.5≤国际标准化比值（INR）≤2.0];组Ⅱ为阿司匹林对照组,观察各组卒中和出血事件的发生率。结果治疗组的血栓发生率明显低于对照组,出血发生率和对照组差异无统计学意义。结论对于脑卒中风险的房颤患者,低强度华法林抗凝能有效减少血栓事件发生,使用安全可靠。     

非瓣膜性心房颤动患者脑卒中危险因素的临床分析

目的回顾性分析非瓣膜性心房颤动患者发生脑卒中的危险因素。方法调查2002年6月至2003年9月在天坛医院住院的非瓣膜性心房颤动患者,通过比较心房颤动合并脑卒中与心房颤动无脑卒中患者的临床特征,筛选心房颤动发生脑卒中的危险因素。结果1)单因素危险因素分析中,与脑卒中相关的危险因素有:年龄>75岁、高血压病史、糖尿病病史、心力衰竭病史;年龄、血糖、血清总胆固醇、血压(收缩压和舒张压);左室收缩功能障碍[左室射血分数(EF)<50%]。2)多因素Logistic分析显示:年龄、高血压病史、左室收缩功能障碍(EF<50%)是脑卒中的独立危险因素。3)438例患者中66.5%接受了抗血栓治疗,其中抗血小板治疗占64.7%,长期抗凝治疗者仅1.8%。结论非瓣膜性心房颤动患者发生脑卒中的独立危险因素为年龄、高血压病史、左室收缩功能障碍(EF<50%)。     

Non-valvular atrial fibrillation and stroke prevention. National Blood Pressure Advisory Committee of the National Heart Foundation

Atrial fibrillation (AF) affects 5% of people older than 65 years. Among patients with AF, the risk of stroke averages about 5% per year. The risk of stroke increases cumulatively with increasing age, previous transient ischaemic attack or stroke, hypertension, diabetes, impaired left ventricular function and a large left atrium. Management aims to identify and treat the underlying cause, control the ventricular rate, restore and maintain sinus rhythm, and minimise the risk of stroke. Warfarin reduces the risk of stroke by about two-thirds, and aspirin by about one-fifth. The risk of anticoagulant-associated haemorrhage increases with serious concomitant disease, and with poorly controlled hypertension and poorly controlled anticoagulation. All patients with chronic AF should be considered for oral anticoagulant therapy, and the decision based on the balance between the risks of thromboembolism and bleeding. The recommended INR (international normalised ratio) is 2.0-3.0. Treating 1,000 "average" AF patients (ie, those with a 5% per year risk of stroke) with warfarin prevents about 30 strokes and causes at least two episodes of major haemorrhage each year. Treating 1,000     

Nonvalvular atrial fibrillation: evidence for a prothrombotic state

OBJECTIVE: To determine whether patients with nonvalvular atrial fibrillation (NVAF) have prothrombotic changes compared with patients in sinus rhythm. DESIGN: Cross-sectional study. Hemostatic function compared in NVAF patients without prior embolic event (transient ischemic attack or embolic stroke) and control subjects without prior thrombotic stroke, and in NVAF patients with prior embolic event and control subjects with prior thrombotic stroke. SETTING: Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals. PATIENTS: A total of 75 NVAF patients (50 without and 25 with prior embolic event) and 42 control patients (31 without and 11 with prior thrombotic stroke) recruited concurrently over 18 months during 1990-91. OUTCOME MEASURES: Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and plasma levels of hemoglobin, fibrinogen, von Willebrand factor antigen, factor VIII, fibrin D-dimer, antithrombin III, protein C, protein S, fibrinopeptide A and prothrombin fragment F1+2. All statistical analyses were performed after adjustments for age and sex. RESULTS: The NVAF patients without a prior embolic event had significantly higher mean hemoglobin and fibrinogen levels (p < 0.001 and p = 0.05, respectively) than the control subjects without prior thrombotic stroke. The 29 NVAF patients not taking warfarin (none had had an embolic event) had significantly lower mean protein C and protein S levels (p = 0.012 and p < 0.001, respectively) and a significantly higher fibrinopeptide A level (p = 0.03, after exclusion of outliers) than the control subjects without prior stroke. The NVAF patients with a prior embolic event had alterations in the hemostatic variables similar to those seen in the control patients with a prior thrombotic stroke. The latter had significantly higher fibrinogen, von Willebrand factor antigen and factor VIII levels (p = 0.04, 0.002 and 0.002, respectively) and significantly lower protein S levels (p = 0.02) than the control subjects without prior stroke. CONCLUSIONS: NVAF patients without a history of an embolic event show evidence of a prothrombotic state compared with patients in sinus rhythm who have not had a thrombotic stroke. NVAF patients with a history of an embolic event show evidence of a prothrombotic state similar to that of patients in sinus rhythm who have had a thrombotic stroke. Prospective studies are needed to determine whether these abnormalities predict higher risk of stroke in individual NVAF patients.     

中国心房颤动患者华法林抗凝治疗社区管理的现状及分析

心房颤动是常见的心律失常之一,是脑卒中的独立危险因素之一。华法林抗凝治疗可显著降低卒中事件的发生。心房颤动作为一种常见的慢性疾病,将华法林抗凝治疗管理纳入慢病管理中,不仅是分级诊疗模式下的大势所趋,也符合国际指南的建议。本文对心房颤动患者华法林抗凝治疗管理的现状及其影响因素进行综述,旨在提高各界对心房颤动患者华法林抗凝治疗社区管理的认识和重视。     

某院2012～2014年老年非瓣膜性房颤合并血栓栓塞并发症患者抗凝治疗现状分析

目的：调查老年非瓣膜性心房颤动（NVAF）住院患者合并血栓栓塞并发症[缺血性脑卒中、短暂性脑缺血（TIA）]的实际抗凝治疗情况。方法采用回顾性病例分析,对2012～2014年该院心血管内科的老年NVAF合并血栓栓塞并发症住院患者,分析其住院期间抗凝治疗情况及国际标准化比值（INR）监测情况,用SPSS20．0统计软件进行结果分析。结果共纳入255例老年NVAF合并血栓栓塞并发症患者,抗凝治疗66例,抗凝治疗率25．88％;抗血小板治疗157例（61．57％）。使用华法林抗凝治疗的患者,INR达标率15．15％。结论老年NVAF合并血栓栓塞并发症患者抗凝治疗率低,以抗血小板治疗为主,抗凝治疗患者住院期间IN R达标率较低。     

心脏机械瓣膜置换术后患者华法林抗凝治疗并发症及其影响因素

目的：了解机械瓣膜置换术后患者华法林相关并发症的相关影响因素。方法：选取2012年1月至12月在宁波市医疗中心李惠利医院行机械瓣膜置换的患者为研究对象，通过电话随访结合门诊随访情况，记录患者一般情况、抗凝情况、凝血功能等指标。对于分类变量采用χ2检验，多因素分析采用logistic回归模型。结果：抗凝药物依从性及房颤在有、无抗凝并发症2组间差异有统计学意义（P＜0.05），瓣膜置换类型、年龄、文化程度、脑梗史、烟酒史、其他长期药物史在2组间差异无统计学意义（P＞0.05）。多因素logistic回归显示房颤及抗凝药物依从性与抗凝并发症显著相关，OR值分别为2.570、4.628。结论：抗凝药物依从性差及房颤是机械瓣膜术后发作抗凝并发症的独立危险因素。     

住院心房颤动患者抗凝治疗依从性及疾病管理需求分析

目的 探讨自然状态下心房颤动(房颤)患者抗凝治疗的依从性、治疗效果以及患者对疾病管理的需求,为开展房颤患者疾病管理,提高抗凝治疗的依从性及治疗效果提供依据.方法 收集2008年1月1日至2008年12月31日在北京安贞医院内科病房住院并且采用抗凝治疗(服华法林)的房颤患者.排除外科、眼科、耳鼻喉科、皮肤科、儿科的住院患者以及住院前已规律服用华法林的患者.通过电子病例回顾收集患者患病及住院治疗信息,通过电话方式了解患者出院后1年时的抗凝治疗情况及对疾病管理的需求.结果 共有268例房颤患者接受电话随访.出院1年时抗凝治疗依从率为54.1%(145/268),性别、年龄、房颤类型、病程以及是否存在缺血性脑卒中病史对服药依从性的影响无统计学意义,相对危险分别为1.74(95% CI 0.67～4.47),0.87(95%CI 0.30～2.53),1.59(95%CI 0.35～1.09),1.09(95% CI 0.61～1.93),0.44(95%CI 0.12～1.60).坚持服用华法林的患者中,60.7%(88/145)每月测量国际标准化测量值(INR),48.3%(70/145)INR值在2.0～3.0,1.4%(2/145)患者出现轻微鼻出血.停止服药的患者中,71.5%(88/123)在出院6个月内停药,主要原因是不知道需要长期服药(35.0%),以及治疗效果不好而换用阿司匹林(24.4%).约80%的患者希望在监测结果的解释、药物调整方面得到指导;73.1%(196/268)患者希望医生能定期随访,89.8%(176/196)患者希望通过电话随访,85.2%(150/176)希望随访频率为1次/月.结论 自然状态下房颤患者抗凝治疗的依从性以及INR达标的比率较低,患者停止服药的主要原因是对长期坚持服药的必要性不了解及治疗效果不理想.在房颤患者中进行疾病管理将满足大多数房颤患者的需求.     

全科医生在心房颤动综合管理中的作用

心房颤动(房颤)是一种临床常见的心律失常,常引起心悸、乏力、胸闷等症状,房颤患者发生卒中、心衰风险增加数倍。在传统的房颤防治模式下,虽然新型口服抗凝药、左心耳封堵术及导管消融术等新治疗方法不断出现,患者的全因死亡率并未得到明显改善,其致残率仍呈上升趋势,医疗负担持续加重,房颤已成为危害人民群众健康的重大公共卫生问题。房颤综合管理是近年提出并证实可明显降低房颤患者住院率及死亡率的治疗策略。该策略需组建一支由全科医生、卒中专家、心脏内科、心脏外科、药学专家等组成的多学科团队,对房颤患者进行综合、全面、连续地管理。全科医生在房颤一级预防中可对其危险因素进行筛查、评估,对居民进行健康教育,促进生活方式、饮食方式的改善,从而控制或消除危险因素对房颤的影响;在房颤二级预防中通过常规体检、门诊复诊等方式做到房颤的早期发现、早期诊断、早期治疗;对已发生房颤的患者,全科医生通过及时有效的抗凝、控制心室率、维持窦性心律等治疗与监测,防治卒中、心衰、出血等并发症。本文从房颤综合管理角度,通过对全科医生在房颤各级预防中的角色进行梳理分析,以期为基层全科医生在房颤管理中的工作方向及流程提供参考和依据。      

华法林抗凝剂量与其影响因素的研究进展

华法林的治疗安全范围窄,剂量的个体差异大,即使同一个体,在不同时期所需的剂量也会不同,但是华法林仍然是目前国际上应用最为广泛的口服抗凝药。临床上因华法林剂量调整不及时而导致的出血或栓塞事件经常发生。华法林主要用于机械心脏瓣膜置换术术后、非瓣膜性心房颤动以及深静脉血栓等患者的抗凝治疗。影响华法林抗凝作用的因素有很多,最主要的有遗传因素、人口学因素以及其他药物因素。该文综述近几年国际上进行的有关影响华法林剂量的许多因素的研究,并介绍基于基因多态性、人口学因素及药物因素的华法林剂量预测模型的最新进展,为指导临床上华法林的个体化用药提供参考。     

北京市非瓣膜心房颤动病人日常抗血栓治疗现况分析

目的 了解北京市非瓣膜心房颤动（房颤）病人日常抗血拴治疗现状,发现房颤病人脑卒中预防存在的问题。方法从北京市城8区（东城区、西城区、海淀区、朝阳区、崇文区、宣武区、石景山区、丰台区）选择8所三级医院和7所二级医院（社区卫生服务中心）。由内科医生对门诊或病房非瓣膜房颤病人采取统一问卷调查。结果 583例病人中75％来源于门诊。其中64．3％来源于三级医院,35．7％来源于社区卫生服务中心。18．9％房颤病人服用华法林,其中39．1％国际标准化测量值（INR）控制在2．0～3．0。68．2％病人华法林服用时间在1年以内。5．7％病人曾经服用华法林。59．3％房颤病人服用阿司匹林,其中85．7％剂量在76～150mg／d,无一例剂量达到325mg／d。18．9％房颤病人未接受任何抗凝治疗。房颤病人不服用华法林的主要原因来自两方面：78．6％病人没有获得抗凝建议,75％以上病人缺乏抗凝知识。房颤病人卒中患病率22．8％,服用华法林者脑卒中患病率22．0％,服用阿司匹林者脑卒中患病率为24．3％,不采取任何措施者脑卒中患病率为21．3％,脑卒中患病率差异无统计学意义（χ^2=1．09,P=0．58）。结论 北京非瓣膜房颤病人抗凝治疗率低于抗血小板治疗率,华法林服用率在我国处于较高水平,但服用时间短,效果欠佳。脑卒中高危房颤病人阿司匹林服用率过高,剂量偏低。提高房颤病人抗凝治疗一方面要改变医生的行为,一方面提高病人抗凝治疗相关知识及治疗依从性。     

Thrombus precursor protein for monitoring anticoagulation in patients with mechanical valve prosthesis

Objective： To evaluate the plasma concentration of thrombus precursor protein （TPP） in patients after mechanical heart valve replacement, and to explore whether it can be used as a marker for monitoring anticoagulation. Methods： Totally 60 patients who took warfarin after mitral valve replacement and 20 control patients with non-valvular heart diseases were subjected in this study. Their plasma TPP concentration and international normalized ratio （INR） were determined, and compared not only between the anticoagulant patients and the control patients, but also between the patients with atrial fibrillaiton （AF, n-37） and the patients with sinus rhythm （SR, n-23） after mechanical valve replacement. The relationship between plasma TPP concentration and INR in the 60 anticoagulant patients was analyzed with linear regression. Results： It was found that the anticoagulant therapy effectively decreased plasma TPP concentration and elevated INR. In the anticoagulant group, the patients with AF had higher plasma TPP concentration than the others with sinus rhythm （P〈0.05）, although there was no significant difference in INR level between these 2 groups of patients （P〉0.05）. No significant correlation was found between plasma TPP concentration and INR in the anticoagulant patients （P〉0.05）. INR did not accord with plasma TPP concentration in several patients. Conclusion： INR can＇t reflect the coagulation status and guide the anticoagulation correctly sometimes; TPP may be a valuable assistant marker for monitoring anticoagulation in patients with mechanical heart valve prothesis; Patients with AF may require higher density of anticoagulation and TPP is strongly suggested to be monitored in these patients.     

Anticoagulation therapy in Chinese patients with non-valvular atrial fibrillation: a prospective, multi-center, randomized,

Background  Non-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).

Methods  A total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests.

Results  The annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P=0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P=0.018, P=0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P=0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P=0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups.

Conclusion  In Chinese patients with NVAF, the warfarin therapy (INR 1.6–2.5) for the prevention of thromboembolic events was superior to aspirin.

     

华法林预防房颤病人血栓性疾病的抗凝强度研究

目的通过前瞻性随机对比研究,评价华法林低强度抗凝预防非瓣膜性房颤发生血栓栓塞的有效性和安全性。方法将102例持续性房颤病人分为华法林低强度抗凝观察组及华法林标准强度抗凝对照组。观察组抗凝目标值INR1.5～2.0,对照组抗凝目标值INR2.1～3.0。常规门诊随访,检测INR调整华法林剂量,并记录两组病人的终点事件及出血事件。结果随访3年,低强度抗凝与标准强度抗凝相比,血栓栓塞事件的发生率无显著差别,而出血并发症低强度抗凝组明显低于标准强度对照组(0.0%vs14%,P0.01)。结论华法林低强度抗凝(INR1.5～2.0)预防非瓣膜性房颤发生血栓栓塞并发症是安全有效的。     

老年非瓣膜性房颤脑卒中危险分层及抗凝现状分析

目的　对非瓣膜性房颤 (NVAF)脑卒中危险分层及基层医院抗凝现状分析。方法　选择NVAF住院患者 1 2 0例并分成ABC三组 ,分别统计脑卒中发生率 (五年 )。将治疗分a组 (未抗凝 ) ,b、c组 (阿司匹林抗血小板聚集 ) ,d组 (华法林抗凝 )。结果　 1 2 0例中A组脑卒中人数 1 3人 (59.1 % )。B组脑卒中人数 2 2人 (2 9.3 % )。C组 1人 (4.3 % )。A组与B组 ,B组与C组比较有明显差异 (P <0 .0 5)。d组脑卒中发生率为 0 ,明显优于a组。阿斯匹林≥ 1 50mg d(c组 ) ,脑卒中发生人数 3人 (1 2 .5 % ) ,与a组比有明显差异 (P <0 .0 5)。结论　A、B组脑卒中发生率明显高于C组 ,口服华法令及阿斯匹林可降低脑卒中发生率。基层医院对NVAF患者抗凝治疗不充分 ,脑卒中发生率高。     

Effect of age upon the induction and maintenance of anticoagulation with warfarin.

We aimed to examine the effect of age upon the control of anticoagulation with warfarin in ordinary clinical practice, using a retrospective examination of routine anticoagulation clinic records from the University Hospital, Nottingham. Considerable over-anticoagulation (international normalisation ratio (INR) > 6.0) during induction occurred in 54 (11%) of 495 patients and was more likely in older patients (p < 0.05). Lesser degrees of over-anticoagulation during induction (INR > 4.0) were also more common in older patients, occurring in 58% of those aged 75 or above. Loading doses of warfarin were not reduced in older patients. INR in the maintenance phase rose with age (p < 0.001) despite lower maintenance doses of warfarin (p < 0.001). An INR > 6.0 in the maintenance phase was noted in 24 (3%) of 739 patients and again was more likely in older patients (p < 0.05). Patients using ambulance transport to the clinic were older than those who did not (p < 0.01) and those aged over 75 had shorter intervals between clinic visits (p < 0.01). We conclude that doctors using warfarin therapy do not take sufficient account of the increased sensitivity of older people to warfarin. Hospital anticoagulant policies need implementation and evaluation.     

Anticoagulant prophylaxis against stroke in atrial fibrillation: effectiveness in actual practice

BACKGROUND: Randomized trials have shown a beneficial effect of anticoagulation with warfarin to prevent stroke in atrial fibrillation. It is not known whether the same effect will be obtained in actual practice. The authors conducted a prospective observational study to evaluate the effect of preventive anticoagulation in patients with atrial fibrillation in 2 practice settings in Montreal. METHODS: Of the 1725 outpatients screened between October 1990 and September 1993 at a community hospital and a university-affiliated hospital, 221 with documented atrial fibrillation were enrolled and followed up for a mean of 27 months. Most (75%) of the patients excluded did not meet the inclusion criteria (because of, for example, an artificial heart valve, mitral stenosis, cardiac transplantation or transient atrial fibrillation); the remainder had not completed enrollment before the end of the study. Following the baseline visit, patients were interviewed by telephone every 6 months, and reported events were confirmed through review of the patients' charts. Hazards for stroke and for stroke and transient ischemic attack (TIA) combined were calculated for each of 4 treatment groups: ASA, warfarin, blended treatment and no treatment, based on the type of anticoagulation therapy patients received during the entire observation period. The blended-treatment group consisted of patients who started on one active therapy and switched to the other or who switched treatments more than once. Corresponding rate ratios (RRs) and 95% confidence intervals (CIs) were calculated with reference to the no-treatment group. Cox proportional hazards analysis was used to adjust for differences in patient characteristics. The rates of bleeding episodes were also analysed. RESULTS: On average, the study patients were older (71.6 [standard deviation 9.3] years) and had a higher prevalence of underlying heart disease (52.0%) than those in the randomized trials. Nineteen patients had a first stroke: 4 in the ASA group, 4 in the warfarin group, 4 in the blended-treatment group and 7 in the no-treatment group, for rates of 5.2, 1.8, 5.3 and 5.9 per 100 person-years, respectively. Only warfarin was associated with a significantly lower risk of stroke compared with no anticoagulant therapy (RR 0.31, 95% CI 0.09-1.00). A similar protective effect of warfarin was found for stroke and TIA combined (2.3 v. 6.7 per 100 person-years; RR 0.34, 95% CI 0.12-0.99); the effect of ASA and blended treatment was not significantly different from no treatment. The rate per 100 person-years of any bleeding was not significantly higher for any treatment group (ASA 2.5, warfarin 3.4 and blended treatment 3.5) compared with the no-treatment group (1.9). Patients receiving warfarin had a significantly greater risk of any bleeding event than patients not receiving anticoagulant therapy (RR 1.79, 95% CI 1.07-3.00). INTERPRETATION: The relative effect of anticoagulant therapy with warfarin in preventing stroke in these practice settings was equivalent to that in the randomized trials, although these patients were older and sicker. This preventive treatment is likely to confer additional benefit as it is more widely prescribed.     

80岁以上非瓣膜性心房颤动患者抗凝方案的调查研究

背景　目前80岁以上非瓣膜性心房颤动患者的抗凝治疗比例普遍偏低,这类人群的抗凝实际情况与指南存在较大差距,抗凝方案的选择缺乏临床证据。目的　调查80岁以上非瓣膜性心房颤动住院患者抗凝方案的选择及预后情况。方法　从HIS系统筛选2016年9月-2018年9月浙江中医药大学附属第二医院首次诊断非瓣膜性心房颤动或既往诊断但未进行抗凝治疗的80岁以上患者516例为研究对象,根据出院时抗凝治疗方案不同将患者分为华法林组、利伐沙班组、达比加群酯组、不抗凝组。收集患者性别、年龄、吸烟史、合并疾病〔高血压、糖尿病、冠状动脉疾病、心肌病、心力衰竭、慢性阻塞性肺疾病（COPD）〕、心房颤动类型（持续性心房颤动、阵发性心房颤动、永久性心房颤动）、缺血性脑卒中史、出血史、估算肾小球滤过率（eGFR）、卒中风险评分（CHA2DS2-VASc评分）、出血风险评分（HAS-BLED评分）、抗凝治疗时间、抗血小板药物应用情况、不良反应（出血事件、缺血性脑卒中、出血性脑卒中、死亡）等情况。采用二元Logistic回归分析探讨患者出现死亡、缺血性脑卒中、出血事件的影响因素。结果　516例患者中接受抗凝治疗137例（26.6%）,其中口服华法林21例（4.1%）、口服利伐沙班67例（13.0%）、口服达比加群酯49例（9.5%）;不抗凝治疗患者379例（73.5%）,其中应用单药抗血小板266例（51.6%）、应用双联抗血小板药物53例（10.3%）、未应用抗血小板药物60例（11.6%）。4组患者性别、年龄、吸烟史、合并疾病（高血压、糖尿病、冠状动脉疾病、心肌病、心力衰竭、COPD）、缺血性脑卒中史、出血史、eGFR、CHA2DS2-VASc评分、HAS-BLED评分、出血（轻度、中度、严重）、出血性脑卒中发生率比较,差异均无统计学意义（P>0.05）。4组患者缺血性脑卒中发生率及死亡率比较,差异均有统计学意义（P<0.05）。华法林组、利伐沙班组、达比加群酯组抗凝治疗时间比较,差异无统计学意义（P>0.05）。二元Logistic回归分析结果显示,CHA2DS2-VASc评分、抗凝治疗方案是缺血性脑卒中的影响因素（P<0.05）,抗凝治疗方案是患者发生死亡事件的影响因素（P<0.05）,HAS-BLED评分是患者发生出血事件的影响因素（P<0.05）。结论　80岁以上非瓣膜性心房颤动患者抗凝治疗比例较低。不抗凝治疗（包括口服抗血小板药物）增加了患者死亡、缺血性卒中风险,而华法林与新型口服抗凝药相比同样安全有效,未增加出血及死亡风险。