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。     

Edoxaban for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation

Introduction: Oral anticoagulation is central to the management of patients with atrial fibrillation (AF) and at least one additional stroke risk factor. For decades, the vitamin K antagonists (e.g. warfarin) remained the only oral anticoagulant available for stroke prevention in AF. The non-vitamin K oral anticoagulants (NOACs) are now available, and these drugs include the direct thrombin inhibitors and factor Xa inhibitors. The latter class includes edoxaban, which has recently been approved for stroke prevention in AF by the United States Food and Drug Administration and the European Medicine Agency. In line with other NOACs, edoxaban avoids the many limitations of warfarin associated with variability of anticoagulation effect and multiple food and drug interactions.

Areas covered: In this review, the currently available evidence on edoxaban in patients with non-valvular AF is discussed. The pharmacology, efficacy and safety, and current aspects of use of edoxaban in patients with non-valvular AF for stroke and thromboembolism prevention are reviewed.

Expert opinion: Phase III trials on edoxaban for stroke prevention in non-valvular AF confirms non-inferiority of edoxaban compared to well-managed warfarin both in terms of efficacy and safety. Currently ongoing and future trials as well as real-world data are warranted to confirm its effectiveness and safety for chronic anticoagulation and improve evidence in other areas which are lacking evidence where NOAC use remains controversial.     

Thromboembolic and bleeding risks in patients undergoing atrial fibrillation ablation: oral anticoagulation perspectives

Introduction: Atrial fibrillation (AF) is a cause of significant morbidity and mortality. Catheter ablation for AF (CAAF) has emerged as an effective treatment option of rhythm control for patients with symptomatic AF. However, the risk of thromboembolism and bleeding in the periprocedural period represent a worrisome complication of this therapy. The reported incidence of thromboembolic and bleeding events associated with CAAF varies from 0.9% to 5% depending on the CAAF strategy and the anticoagulation regimen used in the periprocedural period.

Areas covered: The different anticoagulation regimens used prior to, during, and after CAAF to minimize the risk of thromboembolic and bleeding events are reviewed. The use of uninterrupted oral anticoagulation and appropriate heparin dosing to achieve safe activated clotting time levels are also detailed. A comprehensive approach with assessment of individual risk for thromboembolic and bleeding complications, and understanding the pharmacokinetics of the anticoagulant agents available is also reviewed.

Expert opinion: The key advances done in the periprocedural anticoagulation field include the use of uninterrupted anticoagulation strategies in patients undergoing AF ablation and efforts to simplify the selection of patients who need LAA thrombus screening prior to ablation.     

Long-term outcome in patients with non-valvular atrial fibrillation on dabigatran: a prospective cohort study

ABSTRACT

Introduction: Most studies on thromboembolic and bleeding risk in patients with non-valvular atrial fibrillation (NVAF) exposed to non-vitamin K oral anticoagulants stem from interrogation of insurance databases.

Areas covered: We studied 742 consecutive patients with NVAF who started treatment with dabigatran in three hospitals in Italy. Average follow-up was 1.80 years.

Mean age was 76.2 years. CHA₂DS₂VASc score was 0–1 in 37 (5%), 2 in 97 (13%) and ≥ 3 in 604 (82%) patients. NVAF was permanent in 349 (48%). Overall, 76% of patients remained on treatment over the entire follow-up period. Among 180 patients who discontinued permanently, the most frequent reasons were dyspepsia (33.9%), bleeding (17.8%), and renal worsening (12.1%). About 48% and 74% of permanent discontinuations occurred during the first 6 and 12 months of treatment, respectively. Rates of major events (per 100 patient-years) were 0.75 for stroke, 0.31 for myocardial infarction, 1.50 for all-cause death, and 1.80 for major bleedings. The rate of intracranial bleedings was 0.45 and that of major gastrointestinal bleedings was 0.75.

Expert opinion: This prospective cohort study confirms the low incidence of stroke, major bleeding and intracranial bleeding, and a 76% persistence with treatment, in patients with NVAF treated with dabigatran over about 2 years.     

The hidden costs of anticoagulation in hospitalized patients with non-valvular atrial fibrillation

Introduction: Non-valvular atrial fibrillation (NVAF) and ischemic stroke are collectively associated with annual hospital costs of tens of billions of dollars in the USA. Oral anticoagulant (OAC) treatment with warfarin reduces the risk of stroke in patients with NVAF. Unfortunately, because of the complexity of warfarin therapy and potential for adverse events (AEs), many patients who might benefit go untreated or receive suboptimal therapy, increasing their stroke and/or bleeding risk.

Areas covered: This review explores current hospital costs and resource utilization for NVAF patients on warfarin therapy and the potential impact of newer OACs in this area.

Expert opinion: Many ischemic strokes could be prevented through wider use of OACs. Further, admissions due to anticoagulant-associated AEs could be reduced by optimizing OAC therapy. In the hospital, specialized anticoagulation services can decrease costs by improving the effectiveness of warfarin management, empowering patients through education and optimizing care transitions. With fewer interactions and no dose titration or monitoring required, the novel OACs (NOACs) have the potential to further decrease inpatient resource utilization and costs. It is important that, as data become available, inpatient costs are included in cost–benefit comparisons between warfarin and the NOACs.     

Warfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation

Introduction: Oral anticoagulation is the mainstay for stroke and thromboembolic event prevention in patients with atrial fibrillation (AF). Given limitations of warfarin therapy, non-vitamin K oral anticoagulants have been developed including direct thrombin inhibitors (i.e., dabigatran etexilate). Dabigatran etexilate has been tested thoroughly in terms of efficacy and safety in clinical trials and studies, involving ‘real-world’ cohorts. In this review, currently available evidence in patients with non-valvular AF is discussed.

Areas covered: The pharmacology, efficacy and safety, and current aspects of use of dabigatran etexilate in patients with non-valvular AF are reviewed in a comparative manner to warfarin both for chronic anticoagulation and in different clinical settings.

Expert opinion: Dabigatran etexilate appeared to have several pharmacokinetic and pharmacodynamic advantages over warfarin, as well as a favorable efficacy and safety profile being at least noninferior and often superior to warfarin in patients with non-valvular AF. The latter was shown in the clinical trials, meta-analyses and studies with ‘real-world’ data. Currently ongoing trials will expand the body of evidence on warfarin and will aid decision making in currently controversial areas. Important limitations of dabigatran etexilate include contraindications for its use in patients with prosthetic heart valves and end-stage chronic kidney disease.     

利伐沙班用于超高龄非瓣膜性房颤患者的安全性评价

目的:观察超高龄非瓣膜性房颤(non-valvular fibrillation,NVAF)患者临床特点和抗凝治疗安全性。方法:回顾性分析武汉市第三医院2020年5月至2021年4月接受利伐沙班抗凝治疗的NVAF患者,根据年龄分为观察组(年龄≥80岁)和对照组(<80岁)。观察2组患者发生缺血性脑卒中、心肌梗死、全身性栓塞、大出血及死亡事件的风险。结果:116人完成随访,观察组59人,对照组57人。所有患者至少合并1种慢性疾病,低体质量和肾功能不全是超高龄NVAF患者的生理特点。93.2%患者服用低于标准剂量的利伐沙班,52.5%患者有高或中等依从性。随访结束,2组患者缺血事件、大出血、临床相关非大出血和死亡事件的发生率相似。结论:对于超高龄NVAF患者应充分评估卒中风险和出血风险,低于标准剂量利伐沙班能否达到预期效果需进一步研究。     

影响房颤患者华法林抗凝控制质量的因素分析

目的：了解房颤（atrial fibrillation,AF）患者华法林应用情况,探索影响华法林抗凝控制质量的因素。方法：收集2015年某院门诊应用华法林房颤患者信息,计算每位患者抗凝治疗范围内时间百分比[the percentage time in therapeutic International Normalised Ratio（INR）range,TTR]评价抗凝控制质量,应用χ²检验、t检验及logistic多元回归分析,探讨影响TTR的相关因素。结果：71例患者平均TTR为68.97%±12.12%,超过一半患者（53.52%）的TTR≥70%,单变量分析发现TTR≥70%患者与TTR<70%患者在年龄、职业、文化程度、出血风险（HAS-BLED）、INR检测次数、并发症数目方面均有显著差异（P<0.05）,logistic多元回归分析结果显示职业、INR检测次数、并发症数目与抗凝质量控制显著相关（P<0.05）。结论：职业、INR检测次数、并发症数目是影响房颤患者抗凝控制质量的相关因素。临床药师应做好华法林用药患者的随访工作,提高患者抗凝控制质量。     

Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

Risk of major bleeding in patients with non-valvular atrial fibrillation treated with oral anticoagulants: a systematic review of real-world observational studies

Objective: To conduct a systematic review of real-world (RWD) studies comparing the risk of major bleeding (MB) among patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) or warfarin.

Methods: MEDLINE, Embase, NHS-EED, and EconLit were searched for RWD studies published between January 2003 and November 2016 comparing MB risk among DOACs and warfarin. Proceedings of clinical conferences from 2012 to 2016 were reviewed.

Results: A total of 4218 citations were identified, 26 of which met eligibility criteria. Most studies were retrospective analyses of administrative claims databases and patient registries (n?=?23 of 26); about half were based in the United States (n?=?15). Apixaban showed a significantly lower risk of MB versus warfarin in all eight included studies. MB risk was either significantly lower (n?=?9 of 16) or not significantly different (n?=?7 of 16) between dabigatran and warfarin; there was no significant difference between rivaroxaban and warfarin in all seven included studies. The risk was significantly lower with apixaban versus rivaroxaban (n?=?7 of 7) but not significantly different from dabigatran (n?=?6 of 7). MB risk was significantly lower (n?=?3 of 4) or not significantly different (n?=?1 of 4) with dabigatran versus rivaroxaban. No evidence was identified for edoxaban.

Conclusion: DOACs were associated with similar or lower risks of MB versus warfarin. A lower MB risk was consistently observed for apixaban, but less consistently for dabigatran; MB risk was similar between rivaroxaban and warfarin. Among DOACs, the risk of MB with apixaban was consistently lower than with rivaroxaban, but similar to dabigatran.     

基因分型指导非瓣膜性房颤患者华法林抗凝治疗的研究

目的:评价基因分型指导非瓣膜性房颤(NVAF)患者华法林抗凝治疗的有效性及安全性,探讨基因检测技术在华法林个体化治疗中的意义。方法:纳入符合条件的CHA₂DS₂-VASc≥2分(即卒中高危者)、无用药禁忌且初次使用华法林抗凝的NVAF患者,随机分为常规治疗组和个体化治疗组。常规治疗组给予华法林3 mg·d^-1起始治疗;个体化治疗组检测CYP2C9*2、CYP2C9*3和VKORC1(G-1639A)基因多态性,依据国际华法林遗传药理学联盟的权威公式计算的初始剂量进行治疗;两组常规监测INR,使INR维持在2.0~3.0之间;随访3个月,比较两组INR达标所需时间、主要出血/血栓栓塞事件的差异。结果:两组基线特征比较差异无统计学意义(P>0.05);个体化治疗组INR达标所需时间短(P<0.05);常规治疗组有1例发生脑卒中,6例发生轻微出血(牙龈/鼻腔出血、皮肤淤斑和血尿),两组比较差异有统计学意义(P<0.05)。结论:基于基因多态性的华法林初始剂量预测模型对实现华法林个体化治疗具有一定指导意义,INR达标时间更早且临床疗效更高。     

New evidences for old concerns with oral anticoagulation in atrial fibrillation: focus on dabigatran

Introduction: Nonvalvular atrial fibrillation (NVAF) is associated with a fivefold excess risk of stroke. Antithrombotic therapy is crucial to reduce the risk of stroke. During past decades, vitamin K antagonists (warfarin or acenocoumarol) have been widely used for this purpose. However, they have several disadvantages that limit their daily use in clinical practice.

Areas covered: In patients with NVAF at risk of stroke, the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial demonstrated that, compared with warfarin, dabigatran 150 mg b.i.d. was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage, whereas dabigatran 110 mg b.i.d. exhibited similar rates of stroke and systemic embolism, but lower rates of major hemorrhage. Fortunately, data about dabigatran are not limited to RE-LY trial. In fact, many substudies have been drawn, providing new and important evidences about the benefits of dabigatran.

Expert opinion: The most recent evidences about efficacy and safety of dabigatran in patients with NVAF, focusing on different substudies of RE-LY trial, are reviewed. In summary, dabigatran is beneficial not only in general population with NVAF but also in different subgroups of patients or different clinical settings (i.e., CHADS2 score, INR control, type of AF, elderly, previous transient ischemic attack or stroke, cardioversion and so on).     

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。     

非瓣膜性房颤患者脑梗死急性期抗凝治疗时机分析

目的:调查济宁医学院附属医院非瓣膜性房颤患者脑梗死急性期启动抗凝治疗的时机,为抗凝策略提供参考.方法:采取回顾性病例研究方法,抽取该院2019年1月1日至2019年12月31日出院、诊断为急性脑梗死(或短暂性脑缺血发作)和非瓣膜性房颤的患者为研究对象,记录患者启动抗凝治疗距脑梗死症状出现的时间,并采集相关的临床资料.分...     

新型口服抗凝药在非瓣膜性房颤合并脑血管病中的研究进展

抗凝治疗被认为是非瓣膜性心房颤动(房颤)患者缺血性卒中预防策略的基石。新型口服抗凝药相较于传统口服抗凝药华法林, 具有起效快、半衰期短、药物相互作用少以及无需频繁监测凝血指标等优点, 被普遍应用于预防治疗中, 大幅降低了非瓣膜性房颤患者缺血性卒中的发生风险。但对于合并颅内动脉粥样硬化狭窄、急性缺血性卒中、颅内出血、颅内微出血等增加卒中及出血风险的非瓣膜性房颤患者, 临床抗凝治疗及启动时间的选择无疑是个挑战。本文将对新型口服抗凝药在合并常见脑血管病的非瓣膜性房颤患者中的应用进行综述, 为临床治疗与预防提供参考。     

基层医院临床药师指导华法林抗凝治疗非瓣膜病心房颤动与传统治疗的差异

目的：探讨基层医院临床药师指导华法林抗凝治疗非瓣膜病房颤与传统治疗的差异,为基层医院临床药师开展临床药学服务提供参考。方法：2010年1月-2014年12月,收治非瓣膜病心房颤动患者58例,随机数字表法分成临床药师指导华法林抗凝治疗组28例（指导组）和非临床药师指导华法林抗凝治疗组30例（传统组）。指导组由临床药师采用药学服务模式指导患者华法林抗凝治疗、INR自主监测与剂量调整;传统组由医师依据INR值调整用药剂量、交代药物用法用量和注意事项的临床常规方式进行华法林抗凝治疗;2组目标国际标准化值（INR）均为2.0~3.0（年龄≥75岁者为1.5~2.5）,治疗开始后每间隔5 d在院监测一次INR值。2组患者开始华法林抗凝治疗的第12个月做一次随访调查。结果：2组患者达目标国际标准化值（INR）的比例有显著性差异（P<0.05）;自我监测与剂量调整能力、用药依从性和安全性方面的随访调查,结果有显著性差异（P<0.05）。结论：临床药师采用药学服务模式指导华法林抗凝治疗非瓣膜病心房颤动患者的方法效果显著。