华法令对心房颤动患者的抗凝效果与安全性研究

目的评价华法令用于心房颤动患者抗凝治疗的效果与安全性。方法选择符合研究标准的223例房颤患者,随机分为华法令治疗组112例与阿司匹林对照组111例。治疗组给予华法令片,每次2.5mg,第1天每天3次,第2天每2次,然后每天1次,治疗开始每两天复查1次国际标准化比值(INR)。稳定后每月复查一次INR,依据INR调整华法令用量,使INR保持在2.0~3.0之间。对照组给予阿司匹林50 mg,每天3次。每两周进行1次随访,随访期为1年,观察血栓栓塞事件及有无出血情况。结果华法令组的栓塞发生率为1.8%,阿司匹林组为4.58%,两组差异具有统计学意义(P<0.05),华法令组出血发病率为3.6%,阿司匹林组为1.83%,两组差异无统计学意义(P>0.05)。结论心房颤动的患者使用华法令抗凝治疗,使INR保持在2.0~3.0之间,能有效的预防血栓栓塞事件的发生,不良反应轻微,临床用药安全。     

华法林对中国人心房颤动患者抗栓的安全性和有效性研究

本文通过回顾性分析心房颤动(房颤)患者的抗栓治疗,初步探讨中国人华法林国际标准化率(INR)的合理范围(目前公认的华法林抗凝标准为INR2 .0～3.0 ) ,文章调查4 35例房颤患者应用华法林抗凝及INR监测情况,分析出血和血栓栓塞事件的危险因素及与INR的关系。结果显示:华法林疗程时间中位数7个月,平均剂量为(2 .77土0 .83) mg。共发生出血事件31例(7.11% ) ,其中严重出血5例,轻微出血2 6例。多因素分析中INR≥3为预测出血的独立危险因素(OR=3.74 )。血栓栓塞事件37(17.4 7% )例,发生缺血性卒中或栓塞的危险随INR下降明显增加。本研究显…     

非瓣膜病房颤患者不同强度抗凝的疗效分析

目的分析非瓣膜病房颤患者不同强度抗凝的治疗效果。方法把我院2005年1月到2011年10月有效随访的236例非瓣膜病房颤患者,分成四组,第一组61例,采用阿司匹林(100mg/d)抗凝治疗;第二组54例,采用华法林(INR1.5-2.0)抗凝治疗;第三组63例,采用华法林(INR2.01-2.5)抗凝治疗;第四组58例,采用华法林(INR2.51-3.0)抗凝治疗。最后对四组患者在随访期内的血栓事件及出血事件进行比较。结果第一组患者的栓塞事件发生率为13.1%,高于其他各组,差异有显著性(P<0.05),第四组栓塞事件发生率为1.7%,低于其他组,差异有显著性(P<0.05)。第四组严重血事件发生率10.3%,高于其他各组(P<0.05),而第一组无严重出血事件发生,低于其他组,差异有显著性(P<0.05),但在总出血发生率上四组比较差异无显著性(P>0.05)。结论在非瓣膜病房颤患者抗凝治疗中,华法林预防栓塞疗效优于阿司匹林,随INR强度上升栓塞事件发生降低,但严重出血风险升高,INR1.5-2.5时有效且安全,推荐国人采用。     

121例心房颤动患者抗栓治疗临床分析

目的：回顾性分析121例心房颤动（房颤）患者抗栓治疗情况。观察不同抗栓治疗方案对预防血栓事件有效性。方法：121例房颤患者按华法令治疗组、阿司匹林治疗组及未应用抗栓治疗组分组,观察血栓发生及出血发生情况。结果：华法令治疗组血栓发生率明显低于阿司匹林组及未用抗栓治疗组（P〈0.01）,而出血的并发症发生率三组无明显差别（P〉0.05）。结论：华法令抗凝治疗可明显降低房颤患者血栓栓塞发生事件且安全。     

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。     

慢性心房颤动患者服用华法林时合适INR值探讨

目的评价慢性心房颤动(房颤)患者服用华法林的安全性,探讨华法林抗凝治疗的合适国际标准化比值(INR)。方法本组141例,年龄37~82(61±8.5)岁,每日服用华法林1.25~7.5(2.69±0.74)mg,根据INR值调整华法林用量,观察患者INR值、脑栓塞、体循环栓塞、出血事件、死亡等情况,随访3月~4年(平均2.6年)。结果服用华法林期间发生胃肠道反应终止治疗1例;脑栓塞2例,下肢动脉栓塞1例,INR均<1.7;出血事件4例,INR均>2.5。结论慢性心房颤动患者合理服用华法林是安全有效的,INR的安全范围是1.7~2.5。     

心房颤动的华法林抗凝治疗存在的临床问题

目的：探讨房颤患者华法林抗凝治疗存在的临床问题。方法：分析2006～2008年新疆塔城地区人民医院内科67例心房颤动患者华法林抗凝治疗的随诊临床资料。结果：10例不能定期门诊随诊监测INR,4例发生出血而停药,2例发生血栓及栓塞,3例出现皮疹及皮肤瘙痒而停药,INR未达标率24．1％。结论：房颤患者华法林抗凝治疗存在依从性差,达标率低,受当地医疗条件限制,部分医师和患者对房颤的危险及华法林抗凝治疗的重要性认识不足等临床问题。     

华法令预防房颤致缺血性事件病例的临床观察

目的:观察房颤患者使用华法令对缺血性事件的预防优势。方法:选择2005年3月—2006年1月住院患者中房颤患者60例,随机分为两组,华法令组接受华法令治疗,对照组接受阿司匹林治疗。随访2年,观察缺血性事件的发生情况。结果:华法令组缺血性事件的发生率明显低于对照组,P<0.05。结论:房颤患者应用华法令可以有效地抗栓治疗,并能够明显降低血栓栓塞。尤其是脑卒中的发生,但使用期间应严格定期监测INR,以保证治疗的有效性和安全性。     

心脏机械瓣膜置换术后华法林低强度抗凝疗效观察

目的探讨安徽地区汉族人心脏机械瓣膜置换术后华法林低强度抗凝应用于患者的安全性,为瓣膜置换术后患者给予最佳的华法林抗凝剂量及最佳的INR控制标准提供参考。方法对安徽医科大学第一附属医院2010年1月至2013年1月期间509例安徽省地区汉族人群人工机械瓣膜置换术后的患者给予华法林低强度抗凝治疗。随访期间,记录其PT、INR值及华法林剂量。统计出血及血栓、栓塞等不良事件的发生。结果失访及数据不完整的有40例,数据较完整的有469例,随访1～37个月,平均（18.13±6.02）月,总随访1 960.8人年。男211例,女258例,平均年龄（40.52±13.38）岁,其中行MVR 268例,AVR 115例,DVR 86例。所换瓣膜均为双叶机械瓣膜,其中153枚St.Jude Regent瓣膜,291枚CarboMedics瓣膜,111枚国产GKS瓣膜。结果平均INR为2.11±0.56,平均华法林剂量为（3.124±2.4）mg。共有47例抗凝相关并发症,其中出血事件37例（发生率为1.89%pt-y）,血栓、栓塞事件有10例（发生率为0.51%pt-y）。另外,5例死亡,与抗凝相关有3例。术前患者共有316例合并房颤,43例合并左房血栓。结论安徽省人群瓣膜置换术后患者INR控制在1.8～2.2是合适的,可以有效控制血栓、栓塞及出血等并发症的发生。合并房颤患者及行DVR的患者的抗凝相关并发症发生率较高,此类患者应加大复查频次,及时调整华法林剂量。     

南雄地区房颤抗凝治疗现状分析

目的 回顾分析南雄地区心房颤动(AF)患者的抗凝治疗状况和未抗凝的原因.方法 调查资料完整的AF患者864例.查阅病历资料,全面收集血栓栓塞危险因素、抗凝禁忌证、抗凝药物选择与用法以及未用华法令抗凝治疗的原因等信息.结果 864例AF患者中,88.3%为慢性AF,45.1%的患者具有至少一项血栓栓塞高危因素,46.6%的患者具有至少两项血栓栓塞中危因素.有华法令抗凝治疗指征的AF患者91.8%,只有33.5%采用了华法令抗凝.分析有华法令抗凝治疗指征AF患者未用华法令抗凝治疗的原因,8.6%有抗凝禁忌证,35.4%为医生过分担心出血并发症,56.0%为患者不能按要求监测国际标准化比值(INR),不能监测INR的原因包括:患者依从性差占23.8%,乡镇卫生院没有监测国际标准化比值的条件占32.2%.结论 基层医院,AF患者应用华法令抗凝治疗严重不足,加强医生对华法令抗凝知识的继续教育,改善乡镇卫生院监测国际标准化比值的条件,做好对患者的宣教可能更好地促进AF患者的抗凝治疗.     

Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation?

AIM: To examine the optimal range of International Normalized Ratio (INR) for Chinese patients receiving warfarin for moderate-intensity anticoagulation. METHODS: This was a retrospective cohort study conducted at the ambulatory setting of a 1400-bed public teaching hospital in Hong Kong. The INR measurements and occurrence of serious or life-threatening haemorrhagic and thromboembolic events among patients newly started on warfarin from 1 January 1999 to 30 June 2001 for indications with target INR 2-3 were analysed. The INR-specific incidence of bleeding and thromboembolism were calculated. RESULTS: A total of 491 patients were included, contributing to 453 patient-years of observation period. Forty-seven of the 491 patients experienced 25 haemorrhagic events (5.5 per 100 patient-years) and 27 thromboembolic events (6.0 per 100 patient-years). The percentage of patient-time spent within therapeutic INR range (2-3), INR <2 and INR >3 were 50, 44 and 6%, respectively. The incidence of either haemorrhagic or thromboembolic events was lowest (< or =4 events per 100 patient-years) at INR values between 1.8 and 2.4. CONCLUSIONS: An INR of 1.8-2.4 appeared to be associated with the lowest incidence rate of major bleeding or thromboembolic events in a cohort of Hong Kong Chinese patients receiving warfarin therapy for moderate-intensity anticoagulation.     

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。     

房颤合并冠心病患者服用华法林致INR异常1例的药学监护

目的:探讨临床药师在房颤合并多种疾病的老年患者中开展华法林药学监护的内容和模式。方法:通过1例房颤合并冠心病、尿路感染的老年患者使用华法林后INR异常升高的病例,介绍临床药师分析导致INR异常升高的原因、协助医生制定个体化药学监护计划并实施全程药学监护的过程。结果:经过调整华法林剂量以及其他治疗药物、对患者进行用药教育,患者住院期间未发生出血及栓塞事件,最终达到满意的抗凝治疗效果。结论:对合并多种疾病的房颤患者实施抗凝方案的用药监护,有利于提高患者用药依从性,避免药物不良反应发生,更好地保障用药的有效性和安全性。     

Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation

STUDY OBJECTIVE: To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical pharmacy anticoagulation service in a group model health maintenance organization. SUBJECTS: Thirty nonbleeding patients with international normalized ratios (INRs) ranging from 6.0-10.0. INTERVENTIONS: Patients were randomized to receive either a single oral dose of phytonadione 2.5 mg or placebo. Both groups omitted warfarin doses until the INR became less than or equal to 4.0. MEASUREMENTS AND RESULTS: The mean calculated time to reach an INR of 4.0 was significantly greater in the placebo than the phytonadione group (2.6 vs 1.4 days, p=0.006). Overcorrection of anticoagulation was significantly more common in patients receiving phytonadione. Overt warfarin resistance was not observed in either group after reinitiating warfarin therapy. No major bleeding or thromboembolic complications occurred, and minor bleeding episodes were similar in both groups. CONCLUSION: The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone. Adverse events did not differ between the two groups. Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0. Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection.     

Patient Self-Monitoring of Oral Anticoagulant Therapy

Coumarin derivatives are widely used oral anticoagulants for patients with chronic atrial fibrillation, venous thromboembolism, valvular heart disease, myocardial infarction or a mechanical prosthetic heart valve. Because of the narrow therapeutic window associated with coumarins and the potential for drug interactions, frequent monitoring of anticoagulation is required to maintain the International Normalized Ratio (INR) between 2.0 to 3.5 for most clinical indications. Monitoring of oral anticoagulant therapy is placing a considerable burden on healthcare providers because many patients require life-long treatment with coumarins, and because of an increasing number of elderly patients with conditions that are treated with coumarins. A novel approach that might, in part, address this healthcare need is patient self-monitoring of anticoagulation with a portable coagulometer. Several cohort studies and randomized controlled trials have found that anticoagulation self-monitoring is as good as, or better than, conventional monitoring in a specialized anticoagulation clinic or by a general practitioner. The advantages of anticoagulation self-monitoring include reduced patient inconvenience relating to anticoagulation clinic visits and laboratory monitoring of warfarin therapy, and fewer INR levels outside the therapeutic INR range if INR measurements are preformed more frequently with anticoagulation self-monitoring. Thus, anticoagulation self-monitoring has the potential to reduce the incidence of thromboembolic and bleeding episodes in patients who are receiving long term oral anticoagulant therapy. The potential drawbacks of anticoagulation self-monitoring include the costs of the portable coagulometer. Additionally, self-monitoring is limited to patients who have the cognitive and physical capabilities to perform the technique required for the portable coagulometer.     

Secondary prevention of stroke in patients with nonvalvular atrial fibrillation: optimal intensity of anticoagulation

Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and has become a main cause of cardioembolic stroke. The efficacy of anticoagulation for primary prevention of stroke or transient ischaemic attacks (TIAs) in patients with NVAF has been established by prospective, randomised and controlled trials. Warfarin decreased the frequency of all strokes by 68% and the rate of the combined outcome of stroke, systemic embolism or death by 48%. Anticoagulation with warfarin using international normalised ratios (INRs) ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any of the risk factors identified by the Atrial Fibrillation Investigators (AFI) [previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age (> or = 65 years old), congestive heart failure and coronary artery disease], the American College of Chest Physicians (ACCP) [increased age (> 75 years old), prior stroke, hypertension and heart failure], or the Stroke Prevention in Atrial Fibrillation (SPAF) investigators [women > 75 years old, prior stroke, systolic blood pressure > 160mm Hg, recent heart failure, and fractional shortening < 25% on echocardiography]. For the secondary prevention of stroke, the efficacy of adjusted-dose warfarin therapy has been demonstrated by 2 major randomised trials. SPAF III (INR 2.0 to 3.0) demonstrated a lower incidence of ischaemic stroke or systemic embolism (3.4 %/year) compared with low fixed-dose warfarin plus aspirin (acetylsalicylic acid) [11.9%]. The European Atrial Fibrillation Trial [EAFT] (INR 2.5 to 4.0) showed a lower incidence of all stroke (4.0 %/year) with adjusted-dose warfarin compared with placebo (12.0 %/year). The incidence of major bleeding in the adjusted-dose warfarin group in SPAF III and EAFT was 2.4 and 2.8 %/year, respectively. EAFT incidence rates for the occurrence of a first ischaemic or haemorrhagic complication analysed by INR range indicated that the rate was lowest at INRs of 2.0 to 2.9, and higher with INRs of 3.0 to 3.9. Therefore, the optimal intensity of anticoagulation for prevention of recurrent stroke seems to be an INR of between 2.0 and 3.0, as for primary prevention. Retrospective and prospective studies from Japan reported that in the elderly, haemorrhagic complications occur frequently with INRs above 2.6 and major ischaemic events cannot be prevented at INRs below 1.6. Therefore, an INR target between 1.6 and 2.6 may be an alternative for secondary prevention of stroke in elderly patients with NVAF who have a potential risk of bleeding, to avoid both major ischaemic and haemorrhagic events. Antiplatelets may be administered in patients who are unable to manage taking warfarin properly or who have a high risk of falling and subsequently sustaining a head injury, although the efficacy of antiplatelets for secondary prevention of stroke in NVAF has not yet been established.     

亚洲人群心房颤动华法林抗凝治疗预防脑栓塞的最佳INR值

国内外大量的流行病学调查均显示心房颤动（房颤）的发病率呈明显升高趋势,华法林目前仍是治疗非瓣膜性心房颤动及预防脑栓塞的主要药物。欧美指南建议75岁以下房颤患者对血栓栓塞事件的一级预防及二级预防国际标准化比值（INR）应控制在2．0～3．0,75岁以上房颤患者的出血风险增加,INR应控制在1．6—2．6。亚洲人群华法林肝脏代谢酶活性与西方人群存在明显差异,且相关临床研究显示中等抗凝强度仍能取得与高抗凝强度相同的临床结局,因此华法林剂量应调低。国内初步研究显示,华法林抗凝治疗将INR控制在1．7-2．5范围内是安全有效的,其预防非瓣膜性房颤患者发生血栓栓塞事件的疗效明显优于阿司匹林,但仍需进一步大量临床试验及循证医学提供证据。     

Thromboembolic consequences of subtherapeutic anticoagulation in patients stabilized on warfarin therapy: the low INR study

STUDY OBJECTIVE: To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin. DESIGN: Retrospective, matched cohort analysis. SETTING: Centralized anticoagulation service in an integrated health care delivery system. PATIENTS: A total of 2597 adult patients receiving warfarin from January 1998-December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age. MEASUREMENTS AND MAIN RESULTS: Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation-related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation-related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05). CONCLUSION: Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation.