新型口服抗凝药在心房颤动卒中预防中的研究进展

心房颤动是卒中的独立危险因素,口服抗凝药是预防心房颤动卒中最有效的药物治疗手段。华法林作为近年来心房颤动抗凝治疗的基石一直未被完全取代,却因其治疗上存在的众多限制导致其应用率低或使用不达标等,为解决华法林的这一不足,新型口服抗凝药应运而生,并以其剂量固定、无需常规监测凝血、药物食物相互作用少、出血风险小等优点逐渐受到临床青睐,然而其不足也不容忽视,尚需更多确切的临床实验研究来明确其在临床上的合理应用。现拟通过新型口服抗凝药的抗凝机制、药理学特点及最新试验研究做一简单介绍及比较,并对临床合理选用抗凝药做一简要总结及展望,望能为临床医生针对心房颤动患者合理选用新型口服抗凝药提供帮助。     

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.     

心房颤动患者口服新型抗凝药预防卒中的剂量问题

口服抗凝药是心房颤动患者卒中预防的重要药物.与传统口服抗凝药华法林相比,新型口服抗凝药(novel oral anticoagulants,NOACs)具有高效、安全和无需监测凝血功能的特点,但目前的临床报道显示使用NOACs时的剂量多偏小,其主要原因可能与风险规避和医患偏好不同有关.从安全性和有效性方面分析,NOACs剂量偏大时缺血性卒中或系统性栓塞风险较低,而NOACs剂量偏小时出血风险则较低.考虑到不同事件发生率、致残率和病死率之间的差异,心房颤动患者更适合使用偏大剂量.在选择具体剂量时,考虑到不同药物的特异性,应根据指南推荐、适当参考肾功能并结合患者偏好和个体差异,给予合适的剂量、强度和给药方案以取得最佳临床疗效.     

新型口服抗凝药治疗心房颤动并发心力衰竭研究进展

心房颤动是临床最常见的心律失常之一。2014年美国心脏病学会(ACC)心房颤动指南中就已经明确指出,与华法林相比,新型口服抗凝药(达比加群酯、利伐沙班、阿哌沙班、依度沙班、贝曲西班等)具有药代动力学稳定、药物-药物相互作用较少、主要出血事件较少等优点。心力衰竭是心房颤动未有效控制导致的常见并发症,目前针对心房颤动并发心力衰竭的临床用药尚不明确,现将新型口服抗凝药在治疗心房颤动并发心力衰竭的研究进行综述。     

新型口服抗凝药相关出血的研究进展

新型口服抗凝药物(Novel oral anticoagulants,NOACs)包括直接凝血酶抑制剂(达比加群)和直接Xa因子抑制剂(利伐沙班、阿哌沙班),较传统抗凝药物(例如维生素K拮抗剂华法林、低分子量肝素)更有效且安全。由于它们特殊的作用机制和特异性拮抗药物的匮乏,给临床医师在处理相关出血情况时造成了困难。本文将针对NOACs相关出血风险、监测及出血的相关危险因素、临床处理等作一综述。     

新型口服抗凝药在心房颤动相关认知障碍中的作用

正1新型口服抗凝药的概述针对心房颤动(房颤)高危人群(CHA2DS2-VASc≥2分)预防远期不良事件(血栓栓塞、脑卒中、猝死等),抗凝治疗有着不可替代的作用。目前在非瓣膜病性房颤患者中,传统抗凝药物华法林由于起效慢、常受食物及生活方式的影响、需长期监测国际标准化比值(INR)等原因,临床上已经逐渐被新型口服抗凝药取代。目前新型口服抗凝药主要分为2大类:直接Ⅹa因子抑制剂(如利伐沙班)和直接凝血酶抑制剂(如达比加群),两者无须监测抗凝活性,与药物、食物     

新型口服抗凝药不良反应研究进展

新型口服抗凝药是华法林及其他维生素K拮抗剂的一类替代药物。相较于维生素K拮抗剂,新型口服抗凝药起效快、半衰期短、无需实验室监测、不易受食物及药物影响,主要用于非瓣膜性心房颤动患者缺血性卒中的预防。新型口服抗凝药在临床应用时间较短,报道的最为主要的不良反应为出血,现对近年来涉及新型口服抗凝药主要不良反应的研究进行综述,为临床安全应用提供参考。     

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     

心房颤动患者口服新型抗凝药的获益与风险

新近问世的新型口服抗凝药如:达比加群、利伐沙班(拜瑞妥)、阿派沙班等,为心房颤动患者提供了除华法林的新选择。但由于使用时间较短,某些药理学作用不十分明确,其获益和风险尚需进一步评估。     

从荟萃分析结果看新型口服抗凝药物在心房颤动卒中预防中的获益

抗凝治疗在非瓣膜病性心房颤动(房颤)患者的卒中预防中起关键作用。荟萃分析结果提示,在非瓣膜性房颤患者中,新型口服抗凝药物与华法林相比风险获益比更佳,卒中风险、颅内出血风险及死亡率均显著降低。不同的新型口服抗凝药物的药代动力学及分子机制差异可能显著影响药物在特定人群如老年人、肾功能不全人群中的作用,临床医师应选择个性化治疗方案,平衡血栓和出血风险,尽可能达到最佳的风险获益平衡。     

Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation

The availability of 4 non–vitamin K oral anticoagulants (NOACs), that is, dabigatran, rivaroxaban, apixaban, and edoxaban, has changed the landscape of stroke prevention in patients with atrial fibrillation. This review article provides an overview of the 4 phase III studies that have compared these NOACs, examining major outcomes of efficacy and safety. A range of practical questions relating to the NOACs have emerged, including topics such as patient selection, treating patients with renal impairment, treating elderly patients, and combining anticoagulant therapy with antiplatelet drugs. We also address the interaction of various patient characteristics with the treatments and suggest the features can assist the physician in the choice of a particular NOAC for a particular patient(s).     

New Oral Anticoagulants in Nonvalvular Atrial Fibrillation

The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk‐benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.     

Novel Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.     

Bleeding of New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

Purpose

Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are new oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). We systematically reviewed their risk of major bleeding and efficacy in thromboembolism reduction in AF.

Methods

Eligible randomized controlled trials evaluating NOACs for stroke prevention in AF patients were identified from a systematic search of MEDLINE, EMBASE and the Cochrane database. Risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a Mantel-Haenzel random-effects model.

Results

A total of 13 studies (n?=?61,406) were included. Oral direct factor Xa inhibitors were more effective in reducing stroke and systemic embolism compared to controls (RR 0.71, 95 % CI 0.54–0.92, P?=?0.009) or vitamin K antagonists (VKAs) (RR 0.84, 95 % CI 0.74–0.94, P?=?0.002), with no significant difference in major and clinically relevant non-major (CRNM) bleeding (against controls: RR 0.94, 95 % CI 0.75–1.18, P?=?0.60; against VKAs: RR 0.90, 95 % 0.69–1.17, P?=?0.44). Oral direct thrombin inhibitors were associated with an improved major and CRNM bleeding profile (both comparisons: RR 0.88, 95 % CI 0.78–0.98, P?=?0.02) and a significant reduction in stroke and systemic embolism (against controls: RR 0.79, 95 % CI 0.66–0.93, P?=?0.006; against VKAs: RR 0.78, 95 % CI 0.66–0.93, P?=?0.006).

Conclusions

Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are more effective in reducing stroke and systemic embolism without increasing the risk of major bleeding compared to traditional oral anticoagulants. This favorable risk-benefit balance should be further confirmed by long-term, large-scale safety studies.     

Novel Oral Anticoagulants for Atrial Fibrillation

Three novel oral anticoagulants (NOACS)—dabigatran etexilate, rivaroxaban, and apixaban—have been approved in many countries for stroke prevention in atrial fibrillation, because they are associated with the same or lower rates of stroke, bleeding (particularly intracranially) and death compared with warfarin; and unlike warfarin, they can be given in fixed doses without routine coagulation monitoring. The effects of NOACs compared with warfarin are consistent in almost all populations and patient subgroups studied. Pharmacoeconomic analyses indicate that the NOACs are also cost-effective in Europe and North America. The lack of an antidote to the NOACs in patients who experience major bleeding has not been associated with a worse outcome among patients treated with NOACs compared with warfarin in secondary analyses. Multiple guidelines for the management of AF now recommend the NOACs for stroke prevention among atrial fibrillation (AF) patients at risk for stroke.     

Practical Considerations in the Use of Novel Oral Anticoagulants for Stroke Prevention in Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with an increased risk of stroke. The role of anticoagulation therapy in the prevention of thrombosis and stroke is of critical importance for patients with AF. Limitations with vitamin K antagonists (VKAs), the current standard of care, have led to the development of novel oral anticoagulants (NOACs) that target either thrombin (dabigatran etexilate) or activated factor X (rivaroxaban, apixaban, and edoxaban). In comparison with traditional VKAs such as warfarin, these NOACs offer several pharmacologic advantages, including rapid onset of action, no significant food interactions, low potential for drug–drug interactions, and no requirement for routine coagulation monitoring. Completed phase‐III clinical trials have demonstrated the therapeutic potential of dabigatran, rivaroxaban, and apixaban in comparison with warfarin for stroke prevention in patients with nonvalvular AF (NVAF). While the future utility of NOACs in preventing stroke in patients with NVAF looks promising, several practical issues, including the current lack of a reversal strategy and use of these agents in older patients with renal dysfunction, must be considered. Clinician and patient understanding of such issues will be important for the safe and effective use of NOACs.     

Stroke Prevention in Atrial Fibrillation: A Clinical Perspective on Trials of the Novel Oral Anticoagulants

Atrial fibrillation (AF) is a common heart rhythm disturbance; its incidence increases with age, and it is also an independent risk factor for stroke. Anticoagulation has been proven as the most effective way to reduce the risk of stroke in patients with AF, and vitamin K antagonists have been used for decades as the gold standard treatment. Vitamin K antagonists have a narrow therapeutic window in addition to variable pharmacokinetics and pharmacodynamics, and they frequently interact with food and other drugs, requiring coagulation monitoring to ensure balance between safety and efficacy. The novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban selectively target either thrombin or Factor Xa and have predictable pharmacologic profiles, removing the need for routine coagulation monitoring. This article summarizes phase III data in patient subtypes and discusses controversies surrounding AF management with these agents. Results indicate that NOACs in non-valvular AF have an overall improved efficacy–safety profile compared with warfarin. Significantly fewer fatal bleeding events were observed in patients randomized to rivaroxaban, apixaban, or edoxaban compared with those on warfarin, and significant reductions in the incidence of life-threatening bleeding were observed in patients randomized to dabigatran. All four pivotal trials testing the NOACs against warfarin showed significantly lower rates of intracranial bleeding in patients administered NOACs. These results suggest that wider use of NOACs has the potential to improve outcomes for most patients with AF.     

Advances in Stroke Prevention in Atrial Fibrillation: Enhanced Risk Stratification Combined With the Newer Oral Anticoagulants

Patients with atrial fibrillation (AF) have an increased stroke risk compared with those in sinus rhythm, although the absolute risk for individual patients is modulated by the presence of various additional risk factors. Patient selection for oral anticoagulation for stroke prevention is based on risks of stroke and bleeding. Although CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack) is the most widely used scheme for evaluating stroke risk in patients with AF, several other stroke risk factors are not included; therefore, many patients' stroke risk may be underestimated, contributing to the underuse of anticoagulants. Furthermore, a substantial proportion of patients are categorized as being at moderate risk (CHADS₂ = 1), and there has been some ambiguity regarding optimum thromboprophylaxis in this group. The refinement of CHADS₂, CHA₂DS₂‐VASc (Congestive heart failure, Hypertension, Age 75 years [2 points], Diabetes mellitus, Stroke or transient ischemic attack [2 points], Vascular disease, Age 65 to 74 years, Sex category [female]), considers additional risk factors. Its main advantage is its ability to identify patients truly at low risk of thromboembolism (CHA₂DS₂‐VASc = 0), who are unlikely to benefit from antithrombotic therapy. For all others, an oral anticoagulant may be the preferred approach, simplifying clinical decision making. Implementation of CHA₂DS₂‐VASc may also result in an increased proportion of patients receiving anticoagulation. The emergence of newer oral anticoagulants that can be given without routine coagulation monitoring, with improved benefit–risk profiles vs vitamin K antagonists, promises to simplify therapy for patients with AF at risk of stroke. This, coupled with advances in stroke risk stratification, is expected to improve patient outcomes and reduce the burden of AF‐related stroke.