新型口服抗凝药物研究进展

<正>2001年ATRIA研究报道,年龄<60岁心房颤动的患病率为1%,而年龄>80岁,患病率则可增至10%。心房颤动可使栓塞或脑卒中风险增加5倍,每年绝对风险为1%～20%。《中国心血管病报告2010》指出,我国心房颤动患者脑卒中患病率明显高于非心房颤动人群。华法林虽可降低心房颤动患者脑卒中的风险达2/3,但是,它也有一定的局限性。目前,3种新型抗凝药物引起临     

口服抗凝药物预防心房颤动患者脑卒中的研究进展

<正>心房颤动是临床常见的心律失常,我国拥有心房颤动患者超过800万。脑卒中是心房颤动的严重并发症,与年龄和血压匹配的对照人群相比,无潜在瓣膜性心脏病的心房颤动患者发生脑卒中可能性是对照人群的5倍以上,有瓣膜性心     

新型口服抗凝药物在血栓栓塞性疾病中的应用研究

新型口服抗凝药(NOACs)能够弥补华法林的局限性,具有更好的获益/风险比。临床上对于心房颤动、冠心病及静脉血栓栓塞等疾病的抗凝方案也逐步过渡到NOACs,而且存在许多循证医学证据支持。     

抗凝治疗预防心房颤动血栓栓塞事件分析

目的探讨抗凝治疗预防心房颤动（简称房颤）病人血栓栓塞事件发生的有效性。方法选择1998年1月-2004年6月大同第三医院住院治疗的373例依从性好，能定期随访的房颤病人，据其抗凝用药不同划分为华法林组（104例）、阿司匹林组（173例）与中断治疗组（96例）。随访至少18个月，对3组病人血栓栓塞发生事件进行比较。结果华法林预防房颤病人血栓栓塞形成的有效性优于阿司匹林组（P〈0．05）。结论抗凝治疗可减少血栓栓塞事件，提高病人生活质量。     

心房颤动的血栓栓塞并发症预防和抗凝治疗

AF的血栓栓塞（简称栓塞）并发症，尤其是脑栓塞是AF致死及致残的最主要原因之一，故栓塞的预防是AF治疗的重要目标。复律并维持窦律可消除由AF所致的栓塞，有条件者应积极争取复律。但仍有较大比率的患者无法复律或维持窦律，仅能以控制心室率的方法作为AF的长期维持治疗。AF时有效控制心室率可明显改善患者的心功能及症状，但并不能消除栓塞并发症的发生。据统计，AF栓塞并发症的年发生率为0．55％～20％不等，概与观察人群、病因及年龄不同有关。通常趋势是随年龄增长，发生率增高，80岁以上的高龄患者，脑卒中发生率可达20％以上…     

新型口服抗凝药在治疗血栓栓塞性疾病中的研究进展

血栓栓塞性疾病是由血栓形成和血栓栓塞两种病理过程所引起的疾病,严重威胁人类健康。抗凝药物被广泛应用于血栓栓塞性疾病的预防和治疗,传统的抗凝药包括肝素、低分子肝素、华法林,在预防和治疗血栓栓塞性疾病的有效性已被众多临床研究证实。近年来,各类新型口服抗凝药物不断涌现,如达比加群、利伐沙班、阿哌沙班和依度沙班。现对新型口服抗凝药物的分类及临床应用的研究进展做一综述。     

房颤的血栓栓塞并发症及其预防

作者对房颤患者血栓栓塞并发症的危险因素进行了评述,主要讨论甲状腺毒性房颤、阵发性房颤(及由此转变成慢性房颤)、左房扩大、隐性脑血管栓塞和脑血流降低所起的作用。作者认为,非风湿性慢性房颤患者应予抗凝治疗。     

肺血栓栓塞症抗凝药物应用的研究进展

普通肝素 (UFH)以及华法林是肺血栓栓塞症 (PTE)抗凝治疗的传统药物 ,低分子量肝素(LMWH)与之比较有较好疗效和安全性 ;新一代的抗凝药物如直接凝血酶抑制剂 (DTIs)水蛭素、选择性间接因子Xa抑制剂fondaparinux等有有潜在的应用前景 ,但其疗效与安全性有待评价     

新型口服抗凝药预防心房颤动患者的缺血性卒中

新型口服抗凝药包括直接凝血酶抑制剂和因子Xa抑制药,它们克服了华法林的多个缺点,在非瓣膜性心房颤动患者中预防卒中和体循环栓塞的疗效优于或不逊于华法林,且降低了出血(尤其是颅内出血)风险.然而,目前尚无高效逆转其抗凝作用的药物.文章对目前常用的新型口服抗凝药的药理学特点、临床疗效、并发症及其处理等进行了综述.     

益气活血中药联合新型口服抗凝剂预防心房颤动患者血栓栓塞性疾病有效性及安全性的研究进展

心房颤动是临床常见的心律失常类型,且以非瓣膜性心房颤动(NVAF)为主,其最严重的并发症为血栓栓塞性疾病。新型口服抗凝剂(NOACs)是目前预防心房颤动患者血栓栓塞性疾病的首选药物,但其存在抗凝获益与出血风险的矛盾。目前,采用益气活血中药联合NOACs预防心房颤动患者血栓栓塞性疾病非常普遍,但其安全性的研究报道少见。本文通过分析文献发现,益气活血中药联合NOACs能增强心房颤动患者的抗凝效果,降低血栓栓塞性疾病的发生风险,且可以减少出血风险。     

New oral anticoagulants in atrial fibrillation.

Atrial fibrillation (AF) is a major risk factor for stroke. Currently, acetylsalicylic acid (a platelet inhibitor) and vitamin K antagonists (VKAs; oral anticoagulants), including warfarin, are the only approved antithrombotic therapies for stroke prevention in patients with AF. Although effective, VKAs have unpredictable pharmacological effects, requiring regular coagulation monitoring and dose adjustment to maintain effects within the therapeutic range. The clinical development pathway for novel anticoagulants often involves evaluation of efficacy and safety in a short-term indication, such as the prevention of venous thrombo-embolism (VTE), followed by longer-term VTE treatment studies, and finally chronic indications, including stroke prevention studies in patients with AF. The coagulation pathway provides many targets for novel anticoagulants, including Factor Xa (FXa) and Factor IIa (thrombin). Numerous oral, direct FXa inhibitors are in various stages of clinical development, including rivaroxaban, LY517717, YM150, DU-176b, apixaban, and betrixaban, and are anticipated to overcome the limitations of VKAs. Dabigatran is the only oral direct thrombin inhibitor in late-stage development. Studies of these agents for stroke prevention in patients with AF are planned or ongoing. If approved, they may represent the next generation of anticoagulants, by providing new therapeutic options for stroke prevention in patients with AF.     

非瓣膜性心房颤动应用新型口服抗凝药依从性分析

目的探讨非瓣膜性心房颤动(房颤)患者应用新型口服抗凝药(new oral anticoagulants,NOACs)的依从性及其主要影响因素。方法连续入选2018年1月1日至2018年12月31日于徐州医科大学附属医院心内科住院并行保守抗凝治疗的非瓣膜性房颤性患者272例,根据应用抗凝药种类不同分为华法林组96例和新型口服抗凝药组176例,出院后进行电话随访,比较两组患者抗凝依从性和各自停药原因及影响因素。结果华法林组与NOACs组患者在性别分布、心功能分级、合并疾病方面无统计学差异。平均随访(8.80±3.51)月,NOACs组停药率显著高于华法林组(57.39%vs.22.92%,P<0.001)。对房颤疾病本身及其危害认识不足是两组患者停药的共同主要原因,经济因素、购买因素、出血因素、对疾病缺乏认识对两组患者停用抗凝药均具有显著影响。结论目前新型口服抗凝药服药依从性仍较低,多种因素影响房颤抗凝,其中对房颤缺乏正确认识是导致患者停药的主要原因。     

双重抗血小板与华法林预防低危非瓣膜性心房颤动患者血栓栓塞的对照研究

目的比较阿司匹林联合双嘧达莫与华法林预防低危非瓣膜性心房颤动(NVAF)患者血栓栓塞的有效性和安全性。方法将确诊的125例低危NVAF患者,采用机械抽样法随机分为两组,分别给予调整剂量华法林抗凝治疗[华法林组,69例,目标国际标准化比值(INR)为2.0～3.O]和阿司匹林联合双嘧达莫抗血小板治疗(联合治疗组,56例,阿司匹林100mg 1次/d+双嘧达莫100mg 3次/d)。观察两组患者死亡、血栓栓塞事件(缺血性脑卒中和外周动脉栓塞)及各种出血的发生率。结果随访12～28个月。华法林组失访3例,发生缺血性脑卒中1例,严重出血1例,轻微出血3例;联合治疗组失访2例,发生缺血性脑卒中2例,周围动脉栓塞1例,轻微出血2例,无严重出血病例。与联合治疗组相比,华法林组血栓栓塞事件发生率具有降低趋势,但差异无统计学意义[1.5%(1/66)比5.6%(3/54),P=0.220];出血事件发生率呈现升高趋势,但差异也无统计学意义[6.1%(4/66)比3.7%(2/54),P=0.556]。结论无血栓栓塞高危因素的低危NVAF患者,阿司匹林联合双嘧达莫抗血小板治疗与口服华法林抗凝治疗的疗效相似。     

New anticoagulants for prevention of stroke in patients with atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for ischemic stroke. Antithrombotic therapy using vitamin K antagonists (VKA) is currently prescribed for prevention of ischemic stroke in patients with AF. A narrow therapeutic range and frequent food and drug interactions underly the need for regular monitoring of anticoagulation intensity and impairs the utility and safety of VKA, stimulating a quest for alternative anticoagulant agents. Recently developed anticoagulants include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors rivaroxaban, apixaban, edoxaban, to name those in the most advanced stages of clinical development. This review focuses on advances in the development of novel antithrombotic agents to provide practical information to clinicians on the use of these new drugs in patients with AF.     

Appropriate dosing of nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation

The development of nonvitamin K antagonist oral anticoagulants (NOACs) has been a major advance in therapy for patients requiring oral anticoagulation, particularly for long-term indications such as stroke prevention in atrial fibrillation (AF). The NOACs are generally easier to dose and manage due to less heterogeneity of effect across individuals and fewer drug and food interactions, compared with warfarin. However, the treatment effect of NOACs may vary based on important patient characteristics, particularly renal function. Therefore, the package inserts for these drugs have dosing recommendations for patients with impaired kidney function, which are frequently but not always based on evidence from large-scale, randomized, clinical trials. Furthermore, there is evidence that NOAC dosing inconsistent with the regulatory labeling may be associated with adverse clinical outcomes. This review discusses the evidence supporting the current NOAC dosing, current dosing practices, associated outcomes, and gaps in knowledge regarding use of NOACs in patients with AF.     

非瓣膜性心房颤动患者卒中预防中的抗凝治疗

非瓣膜性心房颤动患者是缺血性卒中的高危人群,临床上主要采用抗凝治疗预防其卒中的发生.然而,常规口服抗凝药华法林因某些限制存在一定的困难.一些新型口服抗凝药,如直接凝血酶抑制药、凝血因子Xa抑制药在非瓣膜性心房颤动患者的卒中预防中显示了其前途.     

Anticoagulation in women with non-valvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials.

AIMS: The risk of stroke is greater among women with atrial fibrillation (AF) than men. Warfarin protects against stroke, but treatment-related bleeding occurs more often in women than in men. METHODS AND RESULTS: SPORTIF III (open label, n=3410) and V (double-blind, n=3922) included 2257 women with AF and one or more stroke risk factors randomized to warfarin [target international normalized ratio (INR) 2.0-3.0] or ximelagatran (36 mg twice daily). Primary outcomes were all stroke (ischaemic/haemorrhagic) and systemic embolic event. Women were older, on average, than men, 73.4+/-8.0 vs. 69.8+/-9.0 years (P<0.0001). More women were >75-years old and women had more risk factors than men had (P<0.0001). The INR on warfarin (mean 2.5+/-0.7) was within target range for 67% of follow-up regardless of gender. Women more often developed primary events [2.08%/year, 95% confidence interval (CI) 1.60-2.56%/year vs. 1.44%/year, 95% CI 1.18-1.71%/year in men; P=0.016). Major bleeding rates were similar (P=0.766) but women experienced more overall (major/minor) bleeding (P<0.001). Warfarin was associated with more overall bleeding in both genders and more major bleeding in women than in men (P=0.001). CONCLUSION: When compared with men with AF, women in these studies were older and had more stroke risk factors. Women were more prone to anticoagulant-related bleeding; the higher rate of thrombo-embolism among women was related to more frequent interruption of anticoagulant therapy.     

新型口服抗凝药在老年静脉血栓栓塞症患者中的应用

静脉血栓栓塞症(VTE)发病率随年龄增加而增长,老年 VTE 患者接受抗凝治疗时出血风险增加,新型口服抗凝药物(NOACs)为老年 VTE的治疗提供了新选择。NOACs主要代表药物包括直接凝血酶抑制剂达比加群和Ⅹa 因子抑制利伐沙班、阿哌沙班、依度沙班,这4种药物均已被批准用于 VTE的治疗。研究表明NOACs对75岁以上老年VTE患者的抗凝疗效与传统抗凝药物效果相当或更佳,而抗凝相关的出血风险并无明显增加,但85岁以上老年 VTE 患者接受达比加群治疗时出血风险明显高于年轻患者。利伐沙班和阿哌沙班用于老年 VTE 患者长期治疗的疗效及安全性也已得到证实。目前研究结果均来源于随机对照试验的亚群分析数据,仍需进一步大规模随机对照试验来充分证实 NOACs在老年 VTE患者中的安全性,而 NOACs缺乏有效的对抗剂和实验室监测手段等问题也有待更好的解决方案。