新型抗凝口服药在非瓣膜性房颤中的研究进展

口服抗凝药物(OAC)已经是预防有高危脑卒中风险房颤患者发生血栓栓塞并发症的基石。新型口服抗凝药(NOAC)的优点包括更大的药代动力学可预测性,与维生素K拮抗剂(VKA)相比具有更少的致命或颅内出血风险,较少的药物-食物相互作用,不需要长时间监测国际标准化比值(INR)等。本文主要就NOAC近期在房颤合并冠脉疾病、脑卒中的二级预防及特异性拮抗剂等方面的研究展开讨论。     

瓣膜性房颤和非瓣膜性房颤的区别以及抗凝策略的差异

心房颤动(房颤)是临床最常见的心律失常之一,可分为瓣膜性和非瓣膜性房颤,但临床医生常将其混淆。根据目前的指南,瓣膜性房颤是指机械瓣置换术后或二尖瓣中-重度狭窄合并的房颤,其他的均称为非瓣膜性房颤。区别瓣膜性和非瓣膜性房颤是由于其血栓形成的机制和栓塞风险及抗凝策略不同,目前瓣膜性房颤只能使用维生素K拮抗剂(华法林)抗凝,而非瓣膜性房颤可选择华法林或新型口服抗凝药(NOACs),首选NOACs。现就瓣膜性和非瓣膜性房颤定义的演变和药物治疗的循证做一综述,旨在让临床医生对瓣膜性和非瓣膜性房颤的诊治有更好的理解。     

新型口服抗凝药在治疗非瓣膜性房颤合并冠心病中的研究进展

<正>心房颤动(简称房颤)是目前临床上最常见的心律失常之一,其发病率随着年龄增长而增加。与51～60岁人群比较,71～80岁人群房颤的发病率增加5倍,80岁以上的高龄老人房颤的发病率增加6倍。我国房颤患病率为0. 77%,80岁以上人群房颤患病率达30%以上,推测我国目前约有1 000万房颤患者^[1]。近年来,房颤合并冠心病的发病率也逐渐增加,全球注册研究GARFIELD研究中国亚组的数据显示,我国32. 4%的房颤患者合并冠心病,10%～25%冠心病患者同时伴有房颤,其中经皮冠状动脉介入治疗(PCI)术后患者中房颤的比例为5%～7%^[2]。     

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。     

老年非瓣膜性房颤患者华法林抗凝强度的研究进展

流行病学调查显示房颤的发病率逐年上升,尤其在老年人中,年龄越大,其发病率和死亡率越高。多个临床试验显示,目前华法林仍是治疗房颤的主要药物。欧美国家的房颤指南建议将国际标准化比值(INR)控制在2.0～3.0,但亚洲和欧美人群之间存在种族差异,应适当降低华法林抗凝强度,尤其是对于有高卒中、高出血风险的老年非瓣膜性房颤(NVAF)患者,INR控制在1.5～2.5是安全有效的,但这一结论仍缺乏大量的临床试验及循证医学依据。     

基因多态性指导非瓣膜性房颤抗凝药物应用的研究进展

抗凝药物是预防房颤病人血栓形成和栓塞最重要的手段,传统的抗凝药华法林受VKORC1、CYP2C9等基因型影响较大,导致不同个体对药物的敏感性差异很大,不利于个体化治疗。现就达比加群酯、华法林的基因多态性个体化应用及注意事项进行综述。     

达比加群酯在非瓣膜性房颤抗凝治疗中的应用

目的比较达比加群酯和华法林在非瓣膜性心房颤动患者的抗凝治疗过程中疗效和安全性。方法对2013年3月—2014年2月收治的54例住院及门诊随诊房颤患者的临床资料进行回顾性分析。结果华法林组31例中发生脑栓塞2例,死亡1例,死亡原因为心力衰竭,轻微出血5例。达比加群酯组23例中发生脑栓塞1例,轻微出血1例。结论达比加群酯在非瓣膜性房颤抗凝治疗中可有效进行抗凝治疗,并有效提高患者依从性。     

非瓣膜性房颤患者华法林抗凝治疗受限因素调研

目的通过分析非瓣膜性房颤患者应用华法林抗凝现状,筛选华法林临床应用受限因素。方法入选聊城市人民医院自2010年5月~2015年5月间住院及门诊具有华法林抗凝适应证的非瓣膜性房颤患者1403例,分为抗凝组和非抗凝组,其中抗凝组127例;非抗凝组1276例。抗凝患者分为达标组、非达标组及中途退出组。分析不同分组中文化程度、对疾病的认知程度以及经济收入等变量因素,进行统计学比较。结果患者个体素质包括文化程度、对疾病的认知程度以及经济收入情况是抗凝组与非抗凝组之间的影响因素(P0.05),且是达标组与非达标组及中途退出组的影响因素(P0.05);定期监测国际标准化比值(INR)是影响达标的因素;担心出血是坚持华法林治疗的影响因素(P0.05)。结论患者的个体素质包括文化程度、对疾病的认知程度以及经济收入是华法林临床应用的受限因素,亦是影响达标的因素,定期监测INR是影响达标的因素,焦虑出血是华法林坚持应用的受限因素。     

老年非瓣膜房颤的口服抗凝治疗进展

心房颤动在老年人占有一定比例，房颤关联的脑中风是老年中突出的一个问题，非瓣膜房颤比其它原因导致的脑中风更严重、死亡率和致残率更高；大规模临床随机试验结果表明，抗凝治疗可明显降低房颤患者的缺血性脑中风发生率，使用华法林比阿司匹林预防缺血性脑中风效果更好，尤其是降低心源性栓塞中风；高龄患者是高危人群，应加强抗凝治疗，但抗凝强度应该是：小剂量的、尽可能低的有效强度，国际标准化比率(intemstional normalized ratio,INR)在1．7～2．5范围更合适。     

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。     

心房颤动卒中抗凝治疗现状与进展

目前我国心房颤动（房颤）患者的人数已超过1000万人。并且随着人口老龄化的加速,房颤患者数还将急剧增大。国外资料显示,房颤患者发生脑卒中的风险是正常人的5～6倍,每年达5％,而发生过脑卒中的患者,每年脑卒中再发的风险为12％。北京地区520例非瓣膜病房颤患者的随访调查发现,     

Frontiers of anticoagulation therapy for atrial fibrillation

In the management of atrial fibrillation (AF), stroke prevention has been proved to play a pivotal role in addition to therapy for concomitant diseases. And, hitherto, anticoagulation by warfarin has been the only effective choice that is known to decrease the stroke rate with ～70% risk reduction. Although the evidence has been rigid, there are many barriers not to make warfarin therapy pervasive. However, the principle of "KISS (keep it short and simple)" seems to alter our situations. Changing the complex pharmacology with warfarin into the simple pharmacology with new anticoagulants would lead us to a new paradigm, where the old book is now rewritten by a new language.     

Underutilization of anticoagulation therapy in chronic atrial fibrillation

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.     

Periprocedural anticoagulation therapy for devices and atrial fibrillation ablation

This EP Wire surveyed clinical practice with regard to the use of antithrombotic therapy in relation to device implantation (pacemakers, ICT, resynchronization therapy) and atrial fibrillation ablation in 71 centres-members of the European Heart Rhythm Association research network. The results of this survey show variation in clinical practice, but reassuringly some consistency with guidelines and consensus recommendations on the management of periprocedure (devices, ablation) antithrombotic therapy.     

利伐沙班对非瓣膜性房颤抗凝治疗有效性和安全性的Meta分析

目的 评价利伐沙班对非瓣膜性房颤患者抗凝治疗的效果及安全性。方法 计算机检索PubMed、EMbase、Medline、CNKI、万方数据库,查找所有比较利伐沙班与华法林对房颤患者抗凝治疗的安全性与有效性的随机对照试验。检索时间均为建库至2015年5月24日。同时手动检索纳入文献的参考文献。采用Cochrance协作网提供的RevMan5.2软件进行Meta分析。结果 纳入文献共3篇,总样本量为15867例。Meta分析示,与华法林相比,利伐沙班明显降低严重出血事件发生率[OR=0.71,95%CI（0.55,0.91）,P=0.007]、颅内出血率[OR=0.63,95%CI（0.45,0.87）,P=0.004]、致死性出血事件发生率[OR=0.51,95%CI（0.33,0.79）,P=0.003]、主要有效终点事件发生率（卒中、系统栓塞）[OR=0.75,95%CI（0.62,0.90）,P=0.002]、次要有效终点事件1发生率（卒中、系统栓塞、血管性死亡）[OR=0.83,95%CI（0.72,0.95）,P=0.008]、次要有效终点事件2发生率（卒中、系统栓塞、血管性死亡、心肌梗死）[OR=0.82,95%CI（0.72,0.93）,P=0.003];而少量出血事件发生率[OR=1.04,95%CI（0.95,1.13）,P=0.43]、上消化道出血率[OR=1.35,95%CI（0.47,3.82）,P=0.58]无明显差异。结论 利伐沙班对房颤的抗凝治疗效果优于华法林,且在危险终点事件上更安全。     

Left atrial thrombus and prognosis after anticoagulation therapy in patients with atrial fibrillation

Background

Anticoagulation therapy reduces the risk of thromboembolic events by two-thirds in patients with atrial fibrillation (AF). The prevalence of left atrial thrombus (LAT) in AF patients with anticoagulation therapy has not been fully investigated.

Purpose

To investigate the prevalence of LAT and its impact on the outcomes in patients with nonvalvular AF after anticoagulation therapy.

Methods

This study consisted of 231 patients with nonvalvular AF who had transthoracic (TTE) and transesophageal echocardiographic (TEE) examinations more than 3 weeks after anticoagulation therapy. The clinical and echocardiographic characteristics were evaluated.

Results

LAT was observed in 13 (8.8%) of 148 patients with sub-therapeutic anticoagulation, and in 3 (3.6%) of 83 patients with sufficient anticoagulation. The presence of LAT was associated with higher CHADS₂ score, decreased LA volume changes and the presence of spontaneous echocardiographic contrast (SEC) in patients with sub-therapeutic anticoagulation. Patients with LAT after sufficient anticoagulation were male with permanent AF who had decreased left ventricular systolic and diastolic function and dilated LA on TTE and SEC, and reduced appendage flow velocity on TEE. Patients with LAT had worse cardiovascular outcomes compared with those without LAT (p = 0.02).

Conclusions

We demonstrated that LAT was a univariate risk factor associated with worse cardiovascular outcomes, which was observed in 8.8% of patients with sub-therapeutic anticoagulation and 3.6% of patients with sufficient anticoagulation.     

高龄心房颤动患者导管消融治疗围术期抗凝方案的研究

目的 探讨高龄心房颤动(房颤)患者行导管消融治疗围术期有效而安全的抗凝方案.方法 选取射频消融治疗的高龄(＞75岁)房颤患者15例(高龄组),术前服用华法林;同期＜75岁射频消融治疗房颤患者15例(非高龄组),根据栓塞风险服用华法林或阿司匹林治疗.术中均用肝素抗凝;高龄组术后以低分子肝素过渡,第3天开始服用华法林,非高龄组术后从第1天开始华法林与低分子肝素重叠应用3d;院外两组服用华法林抗凝3个月.3个月后根据CHADS2评分服用阿司匹林或华法林治疗.门诊随访至少12个月,比较两组凝血酶原时间-国际标准化比值(PT-INR)、6个月内出血和栓塞事件发生率及术后3、6、12个月24 h动态心电图记录心律失常情况.结果 术前高龄组与非高龄组PT-INR值(1.58±0.32对1.37±0.44,P＞0.05),术后INR达标天数[(11.73±3.29)d对(9.71±3.63)d,P＞0.05];左心房内自发显影情况[3例(20.00％)对4例(26.67％),P＞0.05];出血并发症(0对6.67％,P=0.05)、栓塞事件发生率(6.67％对0,P=0.05)差异无统计学意义.两组间术后3、6、12个月心律失常复发情况差异无统计学意义.结论 高龄房颤患者行导管消融治疗术前需严格抗凝并排除心房血栓;术中抗凝与常规用药相同;术后延迟加用华法林治疗同样安全有效.