非瓣膜性心房颤动患者围术期的抗凝治疗

大多数非瓣膜性心房颤动(NVAF)患者需长期应用口服抗凝药物,以减少中风及系统性栓塞的风险。这些患者在接受外科手术或侵入性操作时出血风险增加,部分患者在围术期需暂时中断抗凝治疗。近年来,对于NVAF患者围术期暂时中断抗凝治疗的适应症、时间、暂时中断口服抗凝药物后抗凝治疗的桥接,以及术后抗凝治疗的重新应用已有较多的临床研究。本文简要介绍NVAF患者围术期抗凝治疗的研究现状。     

Self-management of oral anticoagulation in nonvalvular atrial fibrillation (SMAAF study)

Summary Most patients with atrial fibrillation are at risk of suffering thromboembolic events. This risk can be reduced by twothirds by efficient anticoagulation. This prospective multi-center trial investigated whether the quality of treatment can be improved by self-management in patients with atrial fibrillations (SMAAF Study) compared to conventional patient management by the family doctor. Methods Two thousand patients suitable for self-manage- ment were to be randomized into the two arms of the study. In the period of investigation from December 1999 to July 2001, only 202 patients (64.3±9.2 years, 69.3% men) consented to participate. The study was discontinued prematurely since the number of patients was too low. As a consequence, the group comparison is confined to the evaluation of the INR values measured using the two-tailed t test. Results Of the 202 patients included, 101 were assigned to the self-management group (64.6±9.6 years, 71.4% men) and 101 (64.1±8.9 years, 61.4% men, n.s.) were assigned to the group managed by the family doctor. The total number of INR measurements was 2 865. This comprised 2 072 measurements in patients under self-management and 793 in the family doctor group. The values were within the target range significantly more frequently (p=0.0061) in patients under self-management (67.8%) as compared to the family doctor group (58.5%). There was a trend with regard to the time within target range, but the difference was not significant (178.8±126 days as compared to 155.9±118.4 days). In the self-management group, there were two severe hemorrhages, and there was one thromboembolic event in the family doctor group. Conclusion Management of oral anticoagulation by INR self-management in patients with atrial fibrillation is not inferior to conventional care.     

非瓣膜性房颤患者华法林抗凝治疗现况研究

目的探讨非瓣膜性心房颤动患者规范化使用华法林抗凝治疗的现状,分析影响规范化抗凝治疗的因素,进一步提高规范化抗凝治疗的治疗率。方法选取2013-01~2015-12收治的510例非瓣膜性房颤患者的临床资料,采用CHADS2评分法筛选出符合要求使用华法林治疗的患者291例进行回顾性分析,评价其规范化抗凝治疗情况。结果 CHADS2评分≥2分符合要求使用华法林的291例患者中,规范化抗凝治疗只有61例(20.9%)。结论应加强对华法林抗凝治疗效果的认识,提高房颤患者规范化抗凝治疗的控制率和治疗率。     

华发令预防高龄非瓣膜病房颤血栓栓塞的效果及安全性

目的观察华发令预防高龄非瓣膜病心房颤动（房颤）患者血栓栓塞的效果及安全性。方法选择2002年1月2006年1月120例在我科住院的年龄≥75岁房颤患者,随机分为4组,A、B、C 3组华发令口服剂量随国际准化比率（INR）调整,A组INR维持在1.52.0;B组INR维持在2.03.0;C组INR维持在1.52.0的同时给予阿司匹林100 mg/d口服;D组给予阿司匹林100200 mg/d口服,随访时间1848（32±8）月,随访内容使用统一表格,记录各项化验及其他辅助检查结果、终点事件发生时间等。结果A组栓塞事件1例（3%）,D组6例（20%）,B、C组无1例;A、D组出血事件各发生1例（3%）,B组5例（17%）,C组7例（23%）;D组死亡7例,C组死亡1例,P<0.05。结论华发令抗凝强度INR为1.52.0时对预防高龄房颤患者血栓栓塞安全、有效,可供临床选择。     

北京市房山区老年非瓣膜性房颤的华法林抗凝治疗研究

目的：研究适宜剂量的华法林对北京市房山区65岁以上老年持久性非瓣膜性房颤（NVAF）患者的疗效。方法：对纳入研究的870例持久性NVAF患者抗凝治疗资料进行回顾性分析。患者被分为阿司匹林组（471例）和调整剂量华法林（维持INR在2．0～3．0）组（369例）。两组在年龄、性别、伴随病等方面无显著差异。比较两组主要、次要终点事件。结果：入选病例共937例,有效病例870例,失访67例（7．1％）。随访时间（19．2±2．1）个月。华法林组主要终点事件（死亡和缺血性脑卒中）较阿司匹林组降低62％（1．06％：6．52％,P=0．04）。华法林组的缺血性脑卒中较阿司匹林组下降68％（0．42％：4．76％,P=0．04）;华法林组总死亡率低于阿司匹林组（0．42％：3．00％,P=0．02）。包括主要和次要终点的联合终点事件华法林组低于阿司匹林组（2．97％：13．03％,P=0．04）。华法林组出血率较阿司匹林组显著减少（1．69％：12．02％,P=0．04）。结论：对于老年持久性非瓣膜性房颤患者,给予华法林维持INR在2．0～3．0的剂量,可以较阿司匹林更大程度地降低并发症和死亡率,而且是安全的。     

北京市非瓣膜病心房颤动患者血栓栓塞事件的发病风险及影响因素

目的:分析北京市2007至2009年,非瓣膜病心房颤动(NVAF)患者1年内血栓栓塞事件的发病风险及其影响因素。方法:入选北京市出院患者信息系统中,出院日期在2007年1月1日至2009年12月31日之间,18岁及以上且出院诊断包含NVAF的北京市户籍病例,排除接受了射频消融术以及住院期间死亡的病例。通过将出院患者信息系统和北京市死因监测系统进行数据链接和查重,收集1年内这些NVAF患者中发生的血栓栓塞事件。采用Kaplan-Meier法比较不同性别和CHA_2DS_2-VASc评分患者血栓栓塞事件的发生风险,绘制风险曲线,并进行Log-rank检验。采用多因素Cox回归模型分析NVAF患者血栓栓塞事件发生的影响因素。结果:本研究共纳入NVAF患者28 871例,平均年龄(72.7±10.2)岁,其中女性占48.2%,女性患者伴随更多的高血压、充血性心力衰竭和糖尿病。在1年的随访期间,有2 313例(8.0%)患者发生了血栓栓塞事件;发生事件的患者年龄更大,CHA_2DS_2-VASc评分分值更高,伴随更多的高血压、缺血性脑卒中、短暂性脑缺血发作(TIA)、以及糖尿病(P均<0.001),而伴随充血性心力衰竭(P<0.001)、血管疾病(P=0.002)的患者更少。血栓栓塞事件的人年发病率为8.4/100人年,且随CHA_2DS_2-VASc评分分值的升高而升高。Log-rank检验结果显示,男性患者中,CHA_2DS_2-VASc评分在2分以上时血栓栓塞的风险显著增加(P<0.001),而女性患者CHA_2DS_2-VASc评分在3分以上时血栓栓塞的风险显著增加(P=0.004)。多因素Cox回归分析显示,高龄、基线伴随高血压、糖尿病、既往血栓栓塞病史是血栓栓塞事件发生的危险因素。讨论:北京市NVAF患者血栓栓塞事件的人年发病率高于国外人群水平,高龄、基线伴随高血压、糖尿病、既往血栓栓塞病史是事件发生的危险因素,提示应加强对NVAF患者的抗凝治疗和伴随疾病的防治,以降低血栓栓塞事件的发病风险。     

老年非瓣膜性心房颤动抗凝治疗现状分析

目的分析影响老年非瓣膜性心房颤动患者抗凝治疗的因素,为提高老年心房颤动患者抗凝治疗寻求解决方法。方法对2009-10-01—2010-04-30入住北京协和医院,年龄≥65岁的老年非瓣膜性心房颤动患者进行门诊及电话随访,观察分析全因死亡、抗凝比例、未选择抗凝的原因、抗凝终止的原因、不抗凝(抗凝终止)后的抗栓方法等指标。结果共70例连续入院的患者纳入研究,平均随访9.1个月(6.0~13.5个月)。有效随访63例,其中包括年龄<75岁组33例和年龄≥75岁组30例。失访7例(10%)。随访期间共8例(12.7%)死亡,包括年龄<75岁组1例(3%)和年龄≥75岁组7例(23.3%)。有效随访病例中,进行抗凝治疗的仅16例(25.4%),这16例中INR达标13例。8例死亡患者均未进行抗凝治疗,其中6例称大夫未交待抗凝,另2例有明确抗凝禁忌证。结论老年心房颤动患者抗凝比例低,有效抗凝率低。抗凝过程中中断的比例高。解决老年心房颤动患者抗凝过程的具体困难是有效治疗的关键。     

超高龄非瓣膜性房颤患者使用利伐沙班抗凝治疗的单中心经验

目的 探讨利伐沙班在超高龄非瓣膜性房颤患者治疗中的常用剂量及安全性。方法 选择2017年8月至2021年4月于空军特色医学中心心血管内科住院的150例超高龄非瓣膜性房颤患者为研究对象。根据非瓣膜房颤患者出血风险HAS-BLED评分高低确定初始口服利伐沙班剂量,将患者分为低剂量组(10 mg/d, 78例)与中剂量组(15 mg/d, 72例),治疗前后监测血常规、凝血功能、肝肾功能等相关指标,随访1年内的出血事件、不良反应发生率及新发缺血性卒中的发生率。采用SPSS 19.0统计软件进行数据分析。根据数据类型,分别采用t检验、单因素方差分析或χ²检验进行组间比较。结果 连续监测1年,2组患者各有5例患者因肺部感染死亡,差异无统计学意义P>0.05)。治疗前和治疗后第1、3、6、12个月2组患者血红蛋白、血小板计数、凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原、D二聚体和肝肾功能比较,差异均无统计学意义(P>0.05)。所有患者均无再发急性脑梗死或严重出血,出现轻微出血患者经调整用药剂量后症状消失。结论 超高龄老年非瓣膜性房颤患者应用利伐沙班10 mg...     

Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis

OBJECTIVE: To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. METHODS: A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. RESULTS: Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. CONCLUSION: Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.     

不同抗凝强度华法林对80岁及以上心房颤动患者的安全性研究

目的 探讨80岁及以上非瓣膜性心房颤动(房颤)患者使用不同抗凝强度华法林的安全性.方法 130例老年持续性或永久性房颤患者被随机抽签分为3组:(1)低强度抗凝组国际标准化比率(INR)1.5～2.0;(2)中等强度抗凝组INR 2.1～2.5;(3)阿司匹林组.观察3组的出血事件情况及对肾功能的影响.结果 低强度抗凝组(35例)无致命性出血及严重出血,轻微出血2例(5.7%);中等强度抗凝组(32例)致命性出血及严重出血各1例(3.1%),轻微出血4例(12.5%);阿司匹林组(63例)致命性出血3例(4.8%),严重出血3例(4.8%),轻微出血7例(11.1%).3组总出血率比较,差异有统计学意义(χ2=5.13,P＜0.05).低强度抗凝组与中等强度抗凝组对肾功能的影响差异无统计学意义(P＞0.05),但两组明显优于阿司匹林组(P＜0.05).结论 80岁及以上房颤患者中,华法林抗凝INR值维持在1.5～2.0安全性好,对肾功能影响较阿司匹林轻.

Abstract：

Objective To investigate the safety of different intensity anticoagulation therapy of warfarin in preventing thromboembolism in octogenarian patients with nonvalvular atrial fibrillation (NVAF). Methods The 130 patients with persistent or permanent NVAF were randomly divided into three groups: low-intensity warfarin group (35 cases, international normalized ratio, INR (1.5-2.0), moderate-intensity warfarin group (32 cases, INR 2.1-2.5) and aspirin control group (63 cases). The rate of hemorrhagic events and the effect on renal function were observed. Results The incidence of hemorrhage was the lowest in low-intensity warfarin group compared to the other groups with slight bleeding in one case. life-threatening bleeding in one case, severe bleeding in one case and slight bleeding in four cases occurred in moderate-intensity warfarin group. Life-threatening bleeding in three cases, severe bleeding in two cases and slight bleeding in six cases occurred in aspirin control group. There were significant differences in bleeding incidence among the three groups (χ2=5.13,P＜0.05). The low-intensity warfarin group and moderate-intensity warfarin group were superior to the aspirin control group in the effect on renal function (P＜0.05). Conclusions It is safe that the dose of warfarin is maintained at low anticoagulation intensity between INR 1.5 and 2.0 in octogenarians with NVAF.     

Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.

BACKGROUND: Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. METHODS AND RESULTS: Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3+/-10.3 years old). One point each was given for patients with advanced age (>or=75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. CONCLUSION: Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.     

Prothrombotic activity is increased in patients with nonvalvular atrial fibrillation and risk factors for embolism

STUDY OBJECTIVES: The aim of this study was to investigate whether risk factors for embolism would promote thrombus formation in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Hemostatic markers for platelet activity (ie, platelet factor-4 and beta-thromboglobulin [TG]), thrombotic status (ie, prothombin fragments 1 and 2), and fibrinolytic status (ie, d-dimer) were determined in 246 patients with NVAF (mean age, 66.1 years) and 111 control subjects without NVAF (68.3 years). RESULTS: The beta-TG level was higher in NVAF patients than in control subjects. D-dimer levels were higher in NVAF patients having risk factors (mean [+/- SE] d-dimer level, 158.6 +/- 9.2 ng/mL) than in those without risk factors (mean d-dimer level, 92.1 +/- 6.7 ng/mL; p < 0.01) and in control subjects (mean d-dimer level: control subjects with risk factors, 79.1 +/- 10.3 ng/mL; control subjects without risk factors, 31.0 +/- 7.4 ng/mL; p < 0.01). NVAF (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.87 to 8.30; p = 0.0003) and age of >/= 75 years (OR, 5.68; 95% CI, 2.87 to 11.23; p < 0.0001) emerged as predictors of elevated levels of d-dimer, and only NVAF (OR, 10.30; 95% CI, 5.67 to 18.72; p < 0.0001) emerged as a predictor of elevated levels of beta-TG. CONCLUSIONS: NVAF patients whose conditions were complicated with risk factors for embolism could be in the prothrombotic state. Advanced age is a strong predictor of the prothrombotic state in NVAF patients.     

Transesophageal echocardiography risk factors for stroke in nonvalvular atrial fibrillation

Atrial fibrillation is a common arrhythmia, particularly in the older age groups. It confers an increased risk of thromboembolism to these patients, and multiple clinical risk factors have been identified to be useful in predicting the risks of thromboembolic events. Recent studies have evaluated the role of transesophageal echocardiography (TEE) in the evaluation of patients with atrial fibrillation. The purpose of this review is to evaluate the significance of transesophageal echocardiographic findings in the prediction of thromboembolic events, particularly stroke, in patients with nonvalvular atrial fibrillation, with an emphasis on recently reported prospective studies. Aortic plaque and left atrial appendage abnormalities are identified as independent predictors of thromboembolic events. Although they are associated with clinical events, they also have independent incremental prognostic values. Other transesophageal echocardiographic findings, such as patent foramen ovale and atrial septal aneurysm, have not been found to be predictors of thromboembolic events in this patient group. Thus, TEE is a useful tool in stratifying patients with nonvalvular atrial fibrillation into different risk groups in terms of thromboembolic events, and it will likely play an important role in future studies to assess new treatment strategies in high-risk patients with atrial fibrillation.     

Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study

OBJECTIVES: To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation, whether or not they are taking warfarin therapy. DESIGN: Cohort study. SETTING: Integrated healthcare delivery system. Thirteen thousand five hundred fifty-nine adults with nonvalvular atrial fibrillation. MEASUREMENTS: Patient data were collected from automated clinical and administrative databases using previously validated search algorithms. Medical charts were reviewed from patients hospitalized were for major hemorrhage (intracranial, fatal, requiring >or=2 units of transfused blood, or involving a critical anatomic site). Age was categorized into four categories (<60, 60-69, 70-79, and >or=80), and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age, stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage. RESULTS: A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy. Hemorrhage rates rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval (CI) 1.0-1.4) per older age category in patients taking warfarin and 1.5 (95% CI=1.3-1.8) in those not taking warfarin. Intracranial hemorrhage rates were significantly higher in those aged 80 and older (adjusted rate ratio=1.8, 95% CI=1.1-3.1 for those taking warfarin, adjusted rate ratio=4.7, 95% CI=2.4-9.2 for those not taking warfarin) than in those younger than 80. CONCLUSION: Older age increases the risk of major hemorrhage, particularly intracranial hemorrhage, in patients with atrial fibrillation, whether or not they are taking warfarin. Hemorrhage rates were generally comparable with those reported in previous randomized trials, indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients.     

北京地区非瓣膜病心房颤动患者缺血性脑卒中发生率及影响因素的随访研究

目的　调查分析北京地区心房颤动 (房颤 )患者缺血性脑卒中的发生率及其影响因素。方法　对单一中心的 5 2 0例非瓣膜病房颤患者进行随访调查 ,男 346例 ,女 174例 ,入选年龄 4 0～ 10 2(71 2± 12 2 )岁 ,平均随访 (6 75± 4 0 3)年 ,累计随访 32 2 7人年。结果　该组房颤患者脑卒中的年发生率平均为 5 3%。房颤患者各年龄段的脑卒中发生率 :<6 0岁为 1 2 % (95 %可信区间 0 6 7%～1 73% ,合并危险因素者 1 6 % ,不合并危险因素者 1 0 % ) ;6 0～ 70岁为 4 0 % (95 %可信区间 3 38%～4 6 2 % ,合并危险因素者 5 1% ,不合并危险因素者 3 1% ) ;71～ 80岁为 6 7% (95 %可信区间5 96 %～ 7 4 4 % ,合并危险因素者 8 8% ,不合并危险因素者 4 0 % ) ;>80岁为 7 8% (95 %可信区间6 75 %～ 8 85 % ,合并危险因素者 7 7% ,不合并危险因素者 7 9% )。房颤患者脑卒中的发生率与高血压、糖尿病、脑卒中史等危险因素呈正相关 (P值均小于 0 0 5 )。结论　北京地区非瓣膜病房颤患者非抗凝状态下年缺血性脑卒中发生率为 5 3% ;高龄及合并高血压、糖尿病或缺血性脑卒中史为其发生缺血性脑卒中的危险因素。