新型口服抗凝药在非瓣膜性房颤中的应用进展

目的:对新型口服抗凝药(NOACs)在非瓣膜性房颤抗凝治疗中的临床应用和发展进行探讨。方法:收集最新发表的相关文章,对新型口服抗凝药的药理学特性、临床试验结果和临床应用进行分析总结。结果与结论:房颤是临床中最常见的心律失常,对于CHA_2DS_2-VASc评分≥2或既往曾有一过性脑缺血发作(TIA)或有卒中史的患者,应该使用抗凝药物。新型口服抗凝药,与维生素K拮抗剂(VKA)相比,有相似甚至更好的抗凝效果、安全性和便利性。它们具有快速起效,更多可预测的药动学特征,与其他药物相互作用少,饮食对其无明显影响,比华法林导致颅内出血的风险更低。     

新型口服抗凝药与心房颤动的抗凝治疗

心房颤动(房颤)是临床最常见的心律失常,增加脑卒中的发病率和死亡率。抗凝治疗是预防房颤合并脑卒中的有效手段。目前能够长期服用的口服抗凝药物只有华法林,但华法林存在个体差异、复杂的药物和药物及药物和食物之间的相互作用,需要定期抗凝监测和频繁调整剂量,具有局限性。研发新型口服抗凝药成为新的热点,活化凝血因子X抑制剂和凝血酶抑制剂在房颤抗凝领域的研究进展迅速,已经取得了明确的循证医学证据。现将这一领域的研究进展做一综述。     

新型抗凝药物在心脑血管疾病中的临床评价

心房颤动是缺血性脑卒中的重要独立危险因素,抗凝治疗是预防非瓣膜性心房颤动(NVAF)患者缺血性卒中的有效方法。传统抗凝药物华法林疗效肯定但使用不便。直接凝血酶抑制剂及Ⅹa因子抑制剂干扰凝血过程,抗凝作用肯定,具有剂量固定、无需监测凝血指标的优点,受到临床重视。本文对此类新型抗凝药物的药理作用、药代动力学及临床评价等做一综述。     

新型口服抗凝药的特点和临床研究

口服抗凝药在心脑血管血栓疾病的防治中发挥了重要作用,新型口服抗凝药包括直接凝血酶抑制剂达比加群,Xa因子抑制剂利伐沙班、阿哌沙班、贝曲西班和依杜沙班,无需监测、相互作用少,循证医学试验证实在术后血栓、心房颤动,以及急性冠脉综合征中疗效及安全性好于华发林、依诺肝素等,不良反应小。     

新型口服抗凝药治疗非瓣膜病房颤的成本-效用分析

摘要：目的:评价3种新型口服抗凝药物达比加群酯、阿哌沙班、利伐沙班治疗非瓣膜病房颤（NVAF）的成本-效用值,为合理用药及医保目录的评审、药品集中采购、价格谈判等提供决策依据。方法:构建Markov模型模拟NVAF发展过程,依据3种新型口服抗凝药物的国际多中心随机对照试验获得安全性和有效性数据,从文献中获取效用值,运行Treeage Pro 2011软件计算新型口服抗凝药物的成本-效用比,同时进行敏感性分析。结果:新型口服抗凝药治疗NVAF中达比加群酯110 mg成本-效用比18 155.17,达比加群酯150 mg成本-效用比23 034.72,阿哌沙班成本-效用比25 979.16,利伐沙班成本-效用比18 517.53。结论:达比加群酯110 mg在治疗NVAF过程中更具有经济优势,同时利伐沙班在治疗此类疾病相对于达比加群酯110 mg所增加的成本可以接受。     

新型口服抗凝药致消化道出血的研究进展

新型口服抗凝药(NOACs)的抗凝作用机制、药物代谢动力学、临床用药等方面与传统口服抗凝药存在很大差异.本文对NOACs致胃肠道出血(GIB)的可能机制、循证依据、风险因素以及预防和管理策略等方面进行总结归纳,为NOACs的临床应用提供参考依据.NOACs致GIB的风险因素主要与适应证、药品剂量、年龄、种族和既往病史等...     

新型口服抗凝药在伴有慢性肾脏疾病的非瓣膜性房颤患者中抗凝的研究进展

心房颤动是常见的心律失常疾病,持续48 h即可形成血栓,血栓脱落可导致动脉栓塞,其中90%是缺血性脑卒中,而慢性肾脏疾病可进一步增加房颤患者的卒中和出血风险。因此,在伴有慢性肾脏疾病的非瓣膜性房颤患者中的抗凝尤为重要。华法林用于肾功能不全的房颤患者虽可减少血栓栓塞的发生率,但是随着肾功能的恶化,华法林可增加出血的风险,且维持国际标准化比值（INR）在目标范围的时间非常困难。与华法林相比,新型口服抗凝药物能显著地降低卒中、颅内出血和死亡风险。然而新型口服抗凝药物在轻度、中度、重度,甚至血液透析房颤患者的应用仍存在争议。     

基因多态性与新型口服抗凝药个体化用药概述

摘 要新型口服抗凝药(NOACs)由于治疗窗宽、无需常规凝血监测等优势逐渐被广泛使用。近年来,NOACs的药物反应出现个体差异,有报道发现,遗传变异是导致NOACs个体间差异的重要因素,因此研究基因多态性对NOACs药物反应的影响十分必要。通过综述近年来的相关研究探讨基因多态性对新型口服抗凝药的药动学和药效学的影响,指导NOACs个体化用药,提高疗效和安全性,减少不良事件的发生。     

新型抗凝血药物能全面代替华法林吗？

摘 要 查阅国内外关于新型抗凝血药物、华法林在预防和治疗血栓方面的最新文献,结果表明新型抗凝血药物对于中重度肝肾功能损伤的患者需要禁用、或者需要调整剂量、没有拮抗药、没有方便的监测血药浓度的手段,从而限制其使用;华法林在以下几类患者的治疗中有优势：①更换机械瓣膜;②肌酐清除率<25 ml·min^-1;③瓣膜病变;④体质量大于120kg或者小于60kg;⑤肝炎活动期。因此,新型抗凝血药物不能全面代替华法林。     

新型口服抗凝药相关白细胞碎裂性血管炎文献病例分析CSCD

目的分析新型口服抗凝药(NOAC)相关白细胞碎裂性血管炎(LCV)的临床特点。方法检索PubMed、Embase、ScienceDirect、Ovid、Scopus数据库(截至2020年8月),收集报道NOAC相关LCV的病例报告类文献,提取患者相关信息(性别、年龄、原发病、合并疾病、NOAC应用情况、合并用药情况、LCV发生情况、治疗及转归等)进行描述性统计分析。结果共收集到NOAC相关LCV患者13例,美国6例,土耳其、西班牙各2例,希腊、南韩、丹麦各1例;男性8例,女性5例;年龄28~95岁,≥60岁者9例;应用阿哌沙班和利伐沙班者各5例,达比加群酯3例。7例有NOAC用药剂量记录,均在说明书推荐范围内。12例患者有服用NOAC至发生LCV时间的记录,为3~18 d,其中7~10 d者7例。13例患者均出现皮肤病变,表现为紫癜和/或皮疹,累及四肢和躯干者4例、下肢7例、下肢和躯干1例、上肢和躯干1例。12例患者进行了病变部位皮肤活检,11例出现中性粒细胞浸润,1例仅出现嗜酸粒细胞浸润。诊断LCV后,13例患者均停服在用NOAC,其中12例换用其他抗凝药,9例接受糖皮质激素治疗;8例LCV痊愈,5例症状改善。结论NOAC相关LCV多发生在用药7~10 d,主要临床表现为紫癜和皮疹,多累及下肢;停用可疑药物,视病情给予糖皮质激素治疗,预后良好。     

Changing anticoagulant paradigms for atrial fibrillation: dabigatran,apixaban and rivaroxaban

Introduction: Vitamin K antagonists (VKAs) are the main therapeutic agents used to prevent embolic events in patients with atrial fibrillation (AF). Despite their proven efficacy, VKAs are underused and have several limitations. In recent years, there has been great interest in the development of new oral anticoagulants with a more efficient pharmacological profile, first tested in venous thromboembolism prevention and later in AF.

Areas covered: The authors review the pharmacological differences between dabigatran, rivaroxaban and apixaban, and potential subgroups of patients in whom these new drugs would constitute a possible alternative to VKA therapy. Pharmacodynamic and pharmacokinetic data from each compound are analyzed in respect to their potential use in AF. This article provides an exhaustive review of the current status of this topic and the controversies still regarding each drug.

Expert opinion: Apixaban and rivaroxaban are under evaluation for thromboembolic prevention in AF; dabigatran was recently approved for this indication. Therefore, it is important to know the characteristics of these drugs as a potential alternative to VKAs.     

Minor bleeding in patients with atrial fibrillation using a non-vitamin-K antagonist oral anticoagulant

Abstract

Aims

We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin-K antagonist oral anticoagulant (NOAC) therapy.     

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.     

The safety and persistence of non-vitamin-K-antagonist oral anticoagulants in atrial fibrillation patients treated in a well structured atrial fibrillation clinic

Aims To examine the long-term persistence and safety of the non-vitamin-K-antagonist oral anticoagulants (NOACs) dabigatran (D), rivaroxaban (R) and apixaban (A) in patients with non-valvular atrial fibrillation (AF) treated in the framework of a well structured, nurse-based AF unit for initiation and follow-up of NOAC.

Methods Retrospective clinical data were collected for 766 consequent patients from a single cardiology outpatient clinic incorporating the AF unit.

Results The follow-up time, median (q1-q3), was 367 days (183–493) for D patients (n?=?233), 432 days (255–546) for R patients (n?=?282) and 348 days (267–419) for A patients (n?=?251). No significant differences were found between the three groups with regard to age, sex, renal function, or CHA₂DS₂-VASc score. For all bleeding events the incidence rates per 100 patient-years of follow-up (95% confidence interval [CI], p-value) were reported more often for treatment with R (17.2, 12.7–22.8) than for D (7.0, 4.0–11.3, p?=?0.001) and A (8.7, 5.2–13.6, p?=?0.013). The differences remained significant after adjustment for clinically relevant variables. Discontinuation rates (n?=?167) were lower for A (11.5, 7.5–16.8) than for D (30, 23.4–37.9, p?<?0.001) and R (23.9, 18.6–30.1, p?=?0.001), and were mainly attributed to drug-specific side effects and bleedings. The majority of discontinued patients (n?=?142, 85%) proceeded with other types of oral anticoagulants.

Limitation The main limitation of the study is the small patient population with a short follow-up time.

Conclusion In a retrospective study at a single AF clinic, NOACs showed significantly different bleeding rates and varied discontinuation rates when compared to each other, related mainly to agent-specific side effects and bleedings. The majority of patients that discontinued proceeded with other types of oral anticoagulant.     

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.

Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.

Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.     

A rapid evidence assessment of bleed-related healthcare resource utilization in publications reporting the use of direct oral anticoagulants for non-valvular atrial fibrillation

Objective: Non-valvular atrial fibrillation (NVAF), a common cardiac arrhythmia, is associated with high morbidity and carries a substantial economic burden. Historically, vitamin K antagonists (VKAs; e.g. warfarin) have been used for therapy of NVAF, but recently several direct oral anticoagulants (DOACs) have been approved for prevention of stroke in patients with NVAF. This review summarizes the real-world evidence (RWE) for healthcare resource utilization (HRU) in patients receiving oral anticoagulants (VKAs and/or DOACs) for therapy of NVAF.

Methods: A PRISMA-compliant literature search assessed Medline^® and Embase^® databases from 1 January 2011 to 4 May 2017, and the National Health Service Economic Evaluation Database from 1 January 2011 to 31 December 2015. Publications were included if they reported observational data from real-world use of one or more anticoagulant therapies. Outcomes of interest included hospitalizations, length of stay (LOS), mortality and costs.

Results: Twenty-eight publications were included. Apixaban and dabigatran were associated with fewer bleed-related hospitalizations than warfarin. Bleed-related LOS were generally longer for warfarin than for DOACs. Bleed-related treatment costs were lower for patients receiving apixaban or receiving dabigatran than patients receiving rivaroxaban or receiving warfarin. Bleed-related mortality in patients receiving oral anticoagulation for treatment of NVAF were low across all DOACs and warfarin.

Conclusions: The limited available evidence for HRU burden among patients receiving oral anticoagulation for NVAF suggests that DOACs (particularly apixaban and dabigatran) offer some degree of benefit in terms of HRU outcomes, compared with warfarin. Further work is required to understand HRU outcomes in patients receiving DOACs.     

Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients with atrial fibrillation in Sweden and the Netherlands

Objective: There is limited evidence on patients’ adherence and the impact of the prescribed dosing regimen in non-vitamin-K oral anticoagulants (NOACs). We aimed to assess secondary adherence to NOACs and to determine the impact of the dosing regimen in patients with atrial fibrillation.

Methods: Patients using a NOAC between 2009 and 2013 were identified from the nation-wide Swedish Prescribed Drug Register and the Dutch regional IADB.nl database. Patients using a consistent dosage for at least 180 consecutive days were included. Adherence was calculated using the medication possession ratio (MPR) and adjusted for overlapping dates. Adherence was defined as a MPR ≥0.8. Sensitivity analyses were performed using a MPR ≥0.9. Logistic regression was performed to compare secondary adherence and to explore the influence of the dosing regimen.

Results: A total of 5254 Swedish and 430 Dutch NOAC users were included. The mean MPR was 96.0% (SD 7.8%) in Sweden and 95.1% (SD 10.1%) in the Netherlands. Multivariable logistic regression analysis showed that a twice daily regimen had a lower likelihood of being secondary adherent compared to a once daily regimen in Sweden (odds ratio [OR] 0.21 [95% CI 0.12–0.35]).

Limitations: The influence of selection bias introduced by the inclusion criterion of ≥2 dispensations covering at least 180 days could not be excluded.

Conclusions: This study demonstrated that secondary adherence was high in this specific setting among patients with at least two initial dispensations of a NOAC covering a minimum of 180 days. The use of NOACs in a once daily regimen showed higher adherence compared to a twice daily regimen.