阿哌沙班与华法林用于非瓣膜性房颤患者卒中防治的成本效果分析

目的 评估中国非瓣膜性房颤患者使用阿哌沙班或华法林预防卒中的成本效果。方法 基于全球性临床试验ARISTOTLE的研究数据及中国目前医疗成本,建立1年期决策树及长期外推Markov模型的方法,通过计算新型口服抗凝药物阿哌沙班(5 mg bid)及华法林(INR控制在2.0~3.0)的质量调整生命年(quality-adjusted life-years QALYs)及治疗成本,对阿哌沙班用于中国房颤患者卒中预防的成本效果进行了分析和研究。结果 阿哌沙班和华法林的总成本分别为271 826元和40 126元,阿哌沙班组患者可获得的QALYs为6.256,华法林组患者的QALYs为5.614。阿哌沙班较华法林的增量成本效果比(incremental cost-effectiveness ratio,ICER)为360 903元/QALY。ICER>3倍中国人均GDP,但<3倍部分城市人均GDP。敏感度分析显示该成本效果分析结果稳定可靠。结论 在中国目前整体经济形势下,与华法林相比,将阿哌沙班预防非瓣膜性房颤患者卒中预防不具备成本效果优势。目前仅在中国经济发达的某些城市,可推荐阿哌沙班替代华法林成为房颤卒中治疗药物。     

新型抗凝药与华法林用于非瓣膜性房颤患者卒中防治的成本效果分析

目的:评估中国非瓣膜性房颤患者使用新型抗凝药预防卒中的成本效果,为中国房颤患者抗凝治疗药物的合理选用提供理论依据。方法:基于全球性临床试验ARISTOTLE、RE-LY及ROCKET-AF的研究数据及我国目前医疗成本,建立一年期决策树及长期外推Markov模型的方法,通过分别计算3种新型口服抗凝药物阿哌沙班(5 mg bid)、达比加群(150 mg bid、110 mg bid)、利伐沙班(20 mg qd)和华法林的调整质量生命年(QLAYs)及治疗成本,对新型抗凝药物用于中国房颤患者卒中预防的成本效果进行了分析和研究。结果:NOACs治疗的总成本为163586~582710元,使用NOACs患者可获得的质量调整生命年为6.812~7.010。以华法林为参考的增效成本效果分析显示,成本效果比(ICER)为177271~739480元/QLAY,ICER_利伐沙班> ICER_阿哌沙班> ICER_{达比加群150 mg}> ICER_{达比加群110 mg}。3种抗凝药物与华法林比较的ICER均大于我国人均国民生产总值(GDP)的3倍,但小于部分城市人均GDP的3倍。一维敏感度分析显示该成本效果分析结果稳定可靠。结论:目前在我国,与华法林相比,使用新型抗凝药物预防非瓣膜性房颤患者卒中不具备成本效果优势。目前仅在我国经济发达的某些城市,可推荐阿哌沙班或达比加群用于房颤卒中的治疗。     

新适应症

FDA专家推荐达比加群酯用于房颤患者的卒中预防 FDA心血管及肾脏药物专家咨询委员会日前推荐达比加群酯应用于房颤患者卒中预防的适应症。房颤患者出现血栓的风险增高,后者可使卒中风险增加5倍之多,全球每年有多达300万人罹患房颤相关卒中。华法林是目前降低房颤患者卒中风险的标准治疗用药,但非瓣膜性房颤患者在接受华法林治疗过程中需频繁接受凝血指标监测和药物剂量调整,     

华法林用于各卒中风险非瓣膜性房颤患者对其血栓栓塞与出血风险的影响

目的分析非瓣膜性房颤住院患者使用华法林进行抗凝治疗和国际标准化比值(INR)监测状况,以期更好地指导临床抗凝治疗,减少抗凝治疗中血栓栓塞和出血事件发生。方法收集2017年6-12月汕头大学医学院第一附属医院住院治疗的非瓣膜性房颤患者的临床资料、用药情况,监测患者住院期间INR值。采用CHA2DS2-VASc评分对所有患者进行卒中风险评估。随访2年,观察患者因血栓栓塞事件、出血事件再入院情况。结果本研究共纳入病例662例,其中144例使用华法林。在CHA2DS2-VASc评分分层中,中、高危卒中风险患者服用华法林组的INR处于1.5~2.5区间的比例高于无服用组(P<0.05)。在140例服用华法林且INR数据完整患者中,63例(45.0%)INR处于1.0~1.5区间,仅29例(20.7%)INR处于2.0~3.0区间;高危卒中风险患者INR在1.5~2.0组发生血栓栓塞、出血事件再次住院的比例低于INR非1.5~2.0组(P<0.05)。结论临床上华法林使用率低,抗凝强度低。对于中、高危卒中风险患者来说,正确服用华法林有助于将INR控制在1.5~2.5区间。当高危卒中患者的INR处于1.5~2.0区间时可减少血栓栓塞、出血风险的发生。     

小剂量递增法华法林治疗在高龄永久性心房颤动患者抗凝治疗中的作用

心房颤动(房颤,atrial fibrillation,Af)是最常见的心律失常之一,也是脑卒中的独立危险因素.非瓣膜病房颤患者缺血性脑卒中的发生率比正常同龄人高5～6倍,≥75岁的房颤患者更是卒中发生的高危人群,80岁以上房颤患者卒中发病率接近10％[1].根据目前房颤各大治疗指南,在有血栓栓塞危险因素的房颤患者中,应用华法林抗凝治疗是目前唯一可以改善患者预后的药物治疗手段.虽然高龄本身就是房颤抗凝治疗的适应证,但由高龄房颤患者大都合并高血压、肝肾功能不全、可能有卒中史、服用各种药物,根据HASBLED评分同时也是出血高危患者[2].其次,服用华法林初期需要频繁检测凝血功能给患者带来不便,所以华法林在高龄老年患者中的临床应用受到很大限制.本研究探讨小剂量递增法华法林治疗对高龄房颤患者抗凝作用的效果,研究高龄房颤患者华法林抗凝治疗的适宜方法,以期在预防高龄房颤患者血栓性疾病的同时尽量避免出血性疾病的发生,减少凝血功能检测次数,以提高患者治疗的安全性及依从性.     

我院非瓣膜性房颤患者抗凝药物应用现状

摘 要 目的:了解我院非瓣膜性房颤患者抗凝药物应用现状,为临床合理使用抗凝药物提供依据。方法：采集2013年1～12月诊断为非瓣膜性房颤的住院患者共149例,结合血栓栓塞风险评分、出血风险评分、INR在治疗范围的时间比例（TTR）等对其抗凝药物应用情况进行分析评价。结果：149例患者中有144例使用抗凝药物治疗,其中使用华法林的110例（TTR≥60%76例）,使用阿司匹林24例,使用达比加群酯10例。经血栓栓塞风险评分,高危、中危、低危分别有80例、46例、23例。阿司匹林治疗患者中有2例发生脑卒中,华法林治疗患者中8例发生非严重的出血事件。年龄大、合并疾病多、栓塞及出血风险高等因素影响抗凝药物的选择。结论：我院非瓣膜性房颤患者抗凝现状较好,与国外指南推荐使用的抗凝方案基本相符。     

不同类型房颤患者使用新型口服抗凝药物和华法林预防卒中的疗效比较:Meta分析

目的比较新型口服抗凝药物(NOACs)与华法林预防不同类型心房颤动(房颤)患者卒中的有效性和安全性。方法应用计算机从PubMed、 Cochrane图书馆、 Elsevier、 Web of Science、中国知网、万方等电子数据库中检索自建库至2018年7月关于口服抗凝治疗预防房颤患者卒中的随机对照临床试验(RCTs)。获取数据资料后用RevMan 5.3和STATA软件进行荟萃及偏倚统计分析,比较口服抗凝治疗在阵发性房颤与持续性或永久性房颤患者卒中预防的有效性和安全性。结果通过筛选最终纳入了4项大型Ⅲ期RCTs,对其荟萃分析表明在阵发性房颤患者中,无论使用NOACs还是华法林,患者卒中和全身性栓塞发生率[NOACs组(2.58%, 197/7 642) vs.华法林组(3.25%, 193/5 929), RR=0.83, 95%CI:0.61～1.13, P=0.24, I2=57%]和大出血发生率[NOACs组(6.4%, 489/7 642) vs.华法林组(7.12%, 422/5 929),RR=0.88, 95%CI:0.78～1.00, P=0.06, I2=0%]无显著差异。在持续性或永久性房颤患者中,NOACs组卒中和全身性栓塞发生率显著低于华法林组[NOACs组(3.22%, 813/25 197) vs.华法林组(7.12%, 846/20 956), RR=0.82, 95%CI:0.75～0.90, P <0.000 1, I2=0%],同时大出血事件也显著降低[NOACs组(5.5%, 1 386/25 197) vs.华法林组(6.45%, 1 351/20 956), RR=0.85, 95%CI:0.73～0.99, P=0.03, I~2=77%]。结论阵发性房颤患者使用NOACs预防卒中的有效性和安全性与华法林相当,持续性或永久性房颤患者使用NOACs预防卒中的有效性和安全性较华法林好。     

口服抗凝药对房颤患者的卒中预防作用

口服抗凝药是预防房颤患者卒中的有效措施,而房颤患者在伴随其他疾病等特殊情况下,将影响口服抗凝药的作用从而增大卒中或出血风险。本文将对比新型口服抗凝药及华法林对房颤患者卒中预防过程中的获益与风险,旨在为不同房颤患者的抗凝药物选择提供参考。     

一例口服华法林引起出血的病例分析

华法林是最古老的口服抗凝药物,目前仍是长期抗凝治疗中最常用的药物。华法林能有效减少房颤患者发生脑卒中的危险,是目前唯一可以降低房颤患者卒中和栓塞风险、降低病死率的药物。华法林是双香豆素的衍生物,可以抑制新的血栓形成,减少血栓扩大和进展,抑制血栓脱落预防栓塞,有利于清除形成的血栓。华法林抑制凝血因子羧基化,使凝血因子不能与磷脂表面结合,破坏其加速血液凝固[1]。出血风险增高是华法林最常见的不良反应。也是临床医生不能积极使用的主要原因。     

中国非瓣膜性心房颤动患者华法林使用不足的相关因素分析

目的:评估中国首发缺血性卒中或短暂性脑缺血发作(TIA)的已知非瓣膜性心房颤动(NVAF)患者华法林的使用情况及使用不足的相关因素。方法:从中国国家卒中登记数据库(CNSR)中连续筛选首发缺血性卒中或TIA的NVAF患者,筛选已知心房颤动和新发心房颤动患者,评估华法林在适合抗凝治疗的已知心房颤动患者中的使用比例。采用多变量logistic回归模型评估华法林使用不足的相关因素。结果:在筛选出的11 080例首发缺血性卒中或TIA患者中,有996例(9.7%)患者存在NVAF且无抗凝治疗禁忌症,其中有592例既往已知存在心房颤动。在这些患者中,只有96例(16.2%)发病前服用了华法林,496例(83.8%)发病前未服用华法林。在服用华法林的患者中,只有1例患者入院时的国际标准化比值(INR)在治疗范围(2.0～3.0)内。依据CHADS2卒中风险评分,在卒中发生前的低危心房颤动患者中,有近20.2%的患者服用了华法林,而在中危及高危患者中,华法林的服用比例分别只有15.2%和16.4%。年老的和既往存在冠心病病史的患者服用华法林的可能性较小,而发病前服用抗血小板药物的患者更有可能服用华法林。结论:CNSR中首发缺血性卒中或TIA的NVAF患者中,适宜抗凝治疗的患者存在严重的华法林使用不足,即使接受抗凝治疗,达标率也极低。如果发病前给予合适的抗凝治疗并监测,许多由心房颤动导致的卒中和TIA就可避免。     

住院心房颤动患者华法林的使用分析

目的分析比较瓣膜性心房颤动和非瓣膜性心房颤动住院患者华法林使用情况及国际标准化比值（INR）达标状况。方法收集969例住院心房颤动患者的病历资料进行回顾性分析。将患者分为瓣膜性心房颤动和非瓣膜性整体的心房颤动2组,分析2组华法林使用率和达标率的差异及应用华法林患者的INR达标水平。结果瓣膜性心房颤动患者161例中使用华法林者93例,占57.8%;非瓣膜性心房颤动患者808例中使用华法林者214例,占26.5%。93例使用华法林的瓣膜性心房颤动患者中,INR值在2.0～3.0者21例,占22.6%;214例使用华法林的非瓣膜性心房颤动患者中,INR值在2～3者38例,占17.8%。2组患者华法林的使用率比较差异有统计学意义（P＜0.05）,INR达标率比较差异无统计学意义（P＞0.05）。使用华法林的307例心房颤动患者的达标率INR在2.0～3.0者59例,占19.2%;INR＜2.0者230例,占74.9%;INR＞3.0者为18例,占5.9%。结论华法林在心房颤动患者中的使用率低且使用华法林后INR的达标率低。     

More light at the end of the tunnel - apixaban in atrial fibrillation

INTRODUCTION: Subjects with atrial fibrillation are at risk of thromboembolic events. The vitamin K antagonists (e.g., warfarin) are useful at preventing coagulation in atrial fibrillation, but are difficult to use. One of the FXa inhibitors, oral apixaban, has been tested as an anticoagulant in atrial fibrillation. AREAS COVERED: In ARISTOTLE (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) apixaban was compared to warfarin in subjects with atrial fibrillation, and shown to cause a lower rate of stroke or systemic embolism and of major bleeding, than warfarin. In the AVERROES (Apixaban versus acetylsalicylic acid [ASA] to prevent stroke in atrial fibrillations patients who have failed or are unsuitable for vitamin K antagonist treatment) trial, stroke or systemic embolism occurred less often with apixaban than aspirin, whereas the occurrence of major bleeding was similar in the groups. EXPERT OPINION: Apixaban is much easier for subjects with atrial fibrillation to use than warfarin, as it does not require regular monitoring by a health professional, with dosage adjustment. In addition to replacing warfarin in subjects with atrial fibrillation who are unable or not prepared to use warfarin, apixaban has the potential to replace warfarin more widely in the prevention of thromboembolism in subjects with atrial fibrillation.     

某三甲医院心房颤动患者华法林规范化抗凝治疗现状调查分析

目的：了解心房颤动患者抗凝治疗现状,为心房颤动规范化抗凝治疗提供参考。方法：选取皖南医学院弋矶山医院2013年1月~2014年12月非瓣膜性心房颤动患者200例,采用CHA2DS2-VASc和HAS-BLED评分系统对纳入人群进行血栓危险分层和出血风险评估,并依据《2010年欧洲心脏病学会（ESC）心房颤动治疗指南》评价其规范化抗凝情况。结果：CHA2DS2-VASc和HAS-BLED评分分别为（2.73±2.10）分和（1.57±1.13）分。183例（91.5%）患者接受抗血栓治疗,使用华法林抗凝治疗的有74例（37%）,而血栓高危组125例患者中,接受华法林抗凝治疗50例（40%）。华法林抗凝治疗时间（5.78±4.73） d,累积给药剂量为（19.46±18.19） mg,55例（74.32%）患者出院前监测国际标准化比值（INR）,INR达标率为30.9%。结论：心房颤动以华法林抗凝治疗现状不容乐观,应采取有效的干预措施,提高心房颤动患者抗凝治疗规范化程度。     

More light at the end of the tunnel – apixaban in atrial fibrillation

Introduction: Subjects with atrial fibrillation are at risk of thromboembolic events. The vitamin K antagonists (e.g., warfarin) are useful at preventing coagulation in atrial fibrillation, but are difficult to use. One of the FXa inhibitors, oral apixaban, has been tested as an anticoagulant in atrial fibrillation.

Areas covered: In ARISTOTLE (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) apixaban was compared to warfarin in subjects with atrial fibrillation, and shown to cause a lower rate of stroke or systemic embolism and of major bleeding, than warfarin. In the AVERROES (Apixaban versus acetylsalicylic acid [ASA] to prevent stroke in atrial fibrillations patients who have failed or are unsuitable for vitamin K antagonist treatment) trial, stroke or systemic embolism occurred less often with apixaban than aspirin, whereas the occurrence of major bleeding was similar in the groups.

Expert opinion: Apixaban is much easier for subjects with atrial fibrillation to use than warfarin, as it does not require regular monitoring by a health professional, with dosage adjustment. In addition to replacing warfarin in subjects with atrial fibrillation who are unable or not prepared to use warfarin, apixaban has the potential to replace warfarin more widely in the prevention of thromboembolism in subjects with atrial fibrillation.     

房颤患者华法林治疗临床探讨

目的探讨华法林在房颤患者抗凝治疗中的使用方法及临床效果,以减少房颤患者脑卒中的发生率,强调需密切监测标准化比值（INR）,以减少华法林的不良反应。方法总结2004年5月至2009年5月使用华法林抗凝治疗的房颤患者60例,进行回顾性分析。结果房颤患者使用华法林抗凝治疗后脑卒中的年发生率为3．33％、无出血并发症的发生。结论无抗凝禁忌证的房颤患者,均应使用华法林抗凝治疗,但应密切监测服用期间国际标准化比率（INR）,确保华法林的安全使用。     

慢性房颤华法令抗凝治疗的理想INR值探讨

目的:探讨慢性房颤华法令抗凝治疗的理想国际标准化比值(INR)。方法:对115例有血栓栓塞高危因素的慢性房颤患者给予华法令抗凝治疗,定期随访INR,同时观察治疗中发生的血栓栓塞和出血事件。结果:115例患者中有8例共10次发生血栓栓塞事件,7例7次发生与抗凝有关的出血事件,10次血栓栓塞事件中9次发生在INR<1.7,而所有的出血事件都发生在INR>3.5,INR 1.7～3.5时栓塞或出血发生率均较低。结论:INR 1.7～3.5是慢性房颤华法令抗凝治疗较理想的抗凝强度。     

Effect of access to anticoagulation management services on warfarin use in patients with atrial fibrillation

STUDY OBJECTIVE: To determine the effect of access to ambulatory anticoagulation management services (AMS) on the rate of warfarin use in patients with atrial fibrillation. DESIGN: Retrospective medical record review. SETTING: Two ambulatory care clinics in the same managed care system: one with and one without access to pharmacist-managed AMS. PATIENTS: One hundred seventy-eight patients with atrial fibrillation diagnosed between June 2000 and June 2001. MEASUREMENTS AND MAIN RESULTS: Warfarin use was assessed overall and by contraindications and risk factors for stroke. Independent predictors of therapy were identified. The overall rate of warfarin use in atrial fibrillation was higher in the clinic with access to AMS than in the clinic without access (77.9% vs 61.7%, p=0.03). In patients with no known contraindications, warfarin use increased by 20.2% with access to AMS versus no access (80.2% vs 60.0%, p=0.023). Patients aged 65 years or older with one or more risk factors for stroke and no contraindications were more likely to receive warfarin in the clinic with access to AMS than in the clinic without access (85.1% vs 53.8%, p=0.001). Access to AMS was an independent predictor of warfarin use (odds ratio 2.19, 95% confidence interval [CI] 1.05-4.56). Female sex was an independent negative predictor of warfarin use (odds ratio 0.48, 95% CI 0.24-0.96). CONCLUSION: In the managed care setting, use of warfarin for stroke prophylaxis in patients with atrial fibrillation was higher in the ambulatory care clinic with access to pharmacist-managed AMS than in the clinic without access.     

Warfarin in the secondary prevention of thromboembolism in atrial fibrillation: impact of bioavailability on costs and outcomes

BACKGROUND: The bioavailability of warfarin is an important factor affecting the achievement of therapeutic anticoagulation. It is uncertain whether less expensive generic preparations of warfarin would compromise prevention of thromboembolism or increase bleeding risk in patients with atrial fibrillation. OBJECTIVE: To compare the cost effectiveness of strategies using warfarin products with variable bioavailability in patients with a prior stroke or transient ischaemic attack related to atrial fibrillation. DESIGN: A Markov decision-analytic model simulating health and economic outcomes over 1 year using the perspective of a government provincial payer was created. Four strategies were compared (where F = 1 is the assumed bioavailability of the branded/reference product): (i) warfarin F = 1; (ii) warfarin F = 1.25; (iii) warfarin F = 0.80; and (iv) alternating warfarin F = 1.25 and 0.80 every other month. Direct medical costs for drugs, physician fees, laboratory testing and hospitalisation for morbid events were obtained from a government payer, a local accounting system and the medical literature. The cost of warfarin F = 1 was equivalent to the cost of the brand name warfarin and the cost of warfarin F not equal 1 was equivalent to generic warfarin. RESULTS: In our institution, warfarin F = 1 was similar in cost to the other three strategies (Can dollars 1361 vs Can dollars 1334-1613) and may be more effective than switching between generic preparations which have bioavailabilities at the extremes of acceptable limits (thromboembolism and bleeds 7. 1% vs 9.3%). CONCLUSIONS: In patients with atrial fibrillation and a prior ischaemic stroke or transient ischaemic attack, the use of one warfarin agent within the range of acceptable bioavailability can be considered economically attractive from the healthcare perspective.     

Anticoagulation therapy in patients with chronic atrial fibrillation: a retrospective claims data analysis

OBJECTIVES: This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients. METHODS: A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis. RESULTS: Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749). CONCLUSIONS: The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.