抗凝相关性肾病发病及高危因素研究进展

正抗凝相关性肾病(ARN)是近年发现并报道的抗凝剂使用相关并发症,是由过量使用抗凝药物所致的一种新型急性肾损伤(AKI),可进展为慢性肾脏病(CKD)~([1])。临床常用抗凝剂(维生素K拮抗剂、非维生素K拮抗剂、肝素类、新型口服抗凝药物等)为预防血栓栓塞的发生提供可靠保护的同时也增加了患者并发肾损伤的风险。有文献报道显示,维生素K拮抗剂和新型口服抗凝药物引起肾损伤的估计发病率达20.5%,每年因CKD抗凝治疗而引起ARN的发生率可达26%,     

左心房内径与非瓣膜性房颤患者缺血性脑卒中风险的相关性分析

目的探讨左房内径(LAD)与老年非瓣膜性房颤患者缺血性脑卒中风险的关系。方法将325例非瓣膜性房颤患者根据缺血性脑卒中史分为房颤伴脑卒中组(n=127)和房颤不伴脑卒中组(n=198),比较2组血糖、肌酐清除率、血脂、合并疾病、LAD等临床资料,采用Logistic回归分析评估LAD与缺血性脑卒中风险的相关性,并绘制受试者工作特征(ROC)曲线,评估LAD对缺血性脑卒中的预测价值。结果房颤伴脑卒中组的平均年龄、女性患者比率、合并心力衰竭及高血压患者比率、房颤血栓危险度(CHA_2DS_2-VASc)评分、LAD、肌酐(Cr)、尿酸(UA)均高于房颤不伴脑卒中组,阵发性房颤患者比率及估算的肾小球滤过率(e GFR)水平低于房颤不伴脑卒中组(P 0.05或P 0.01)。多因素Logistic回归分析结果显示,LAD与缺血性脑卒中风险呈正相关(P 0.01)。ROC分析表明,LAD对缺血性脑卒中风险有一定的预测价值(P 0.01),LAD联合CHA_2DS_2-VASc评分的ROC曲线下面积(AUC)为0.904。结论 LAD与非瓣膜性房颤患者缺血性脑卒中风险呈正相关,LAD联合CHA_2DS_2-VASc评分可以更好预测非瓣膜性房颤缺血性脑卒中风险。     

房颤相关卒中后的治疗:利伐沙班vs华法林

正心房颤动(a-fib)相关的急性缺血性脑卒中患者,有很高的复发性卒中和颅内出血的风险。本研究比较了非维生素K拮抗剂的口服抗凝血剂(NOAC)——利伐沙班,与剂量调整后的华法林,在轻度房颤相关急性缺血性卒中患者中的疗效和安全性。受试者是患急性缺血性卒中合并非瓣膜性房颤的患者。受试者被随机分为服用利伐沙班或华法林,华法林组国际标准化比率(INR)调整至2-3。利伐沙班组,前5天每日服用利伐沙班10mg,此后每日20mg。华法林组药物控制在INR2-3。在第4周,进行MRI检查以     

肾小球滤过率对心源性卒中老年患者长期不良预后的预测研究

目的探讨肾小球滤过率(eGFR)与非瓣膜性房颤致心源性卒中老年患者长期不良预后的关系。方法纳入2013年1月-2016年1月于首都医科大学宣武医院神经内科住院的非瓣膜性房颤致心源性卒中老年患者195例(年龄≥65岁),使用肾脏病饮食改良(MDRD)简化公式计算肾小球滤过率估计值(eGFR),按照eGFR60ml/(min·1.73m2)为肾功能不全,分为肾功能不全组(34例)和无肾功能不全组(161组),出院后1年通过电话或门诊随访,观察卒中不良结局,包括全因死亡、卒中复发、联合终点事件(卒中或死亡)、卒中性残疾。结果 (1)肾功能不全组(eGFR60ml/(min·1.73m2)患者中,年龄≥75岁者的比例高于无肾功能不全组[eGFR≥60ml/(min·1.73m2)]患者,差异有统计学意义(85.3%(29/34)比54.0%(87/161),P0.05);(2)肾功能不全组和无肾功能不全组比较,出院后1年不良预后结局事件发生率的差异有统计学意义(52.9%比32.9%,χ2=4.860,P=0.0270.05);(3)多因素Logistic分析显示,非瓣膜性房颤致心源性卒中老年患者1年内发生卒中不良结局事件与患者出院时NIHSS有关(OR=1.141,P0.05)。结论患者出院时NIHSS评分可以预测非瓣膜性房颤致心源性卒中老年患者长期不良预后结局,与患者eGFR低于60ml/(min·1.73m2)无关。     

高血压合并房颤患者降压及抗凝药物治疗研究进展

高血压和心房颤动有着密切的关系,在高血压合并房颤的患者中,血压的良好控制以及抗凝药物的合理使用是治疗的重要措施。以ACEI/ARB类药物为基础的降压治疗可以明显减少高血压患者新发房颤的发生。新型口服抗凝剂的出现相比传统药物华法林更减少患者卒中和栓塞事件的发生率,同时针对不同作用机制新型口服抗凝剂的特效拮抗剂的出现也进一步减少新型口服抗凝剂出血副作用的发生。     

房颤患者华法林抗凝治疗177例

目的回顾性分析心房颤动（房颤）患者的抗凝治疗与卒中情况。 方法调查2015年8月1日至2017年6月30日苏北人民医院住院房颤患者301例的病例资料,记录性别、年龄、主要诊断、合并疾病情况、CHA2DS2-VASc评分、HAS-BLED评分、INR值、华法林剂量、新型口服抗凝剂（NOAC）、阿司匹林使用情况、血栓栓塞事件、出血事件情况,分析抗凝治疗的规范性及其与临床后果的关系。 结果住院房颤患者平均年龄（72±11）岁,房颤类型以非瓣膜型房颤为主,占93.7%（282/301）,58.8%的房颤患者采用口服华法林抗凝治疗,4%接受NOAC抗凝治疗。华法林抗凝治疗组缺血性卒中发生率显著低于未抗凝治疗组差异具有统计学意义（13.0% vs 20.5%,P=0.025）。瓣膜型和非瓣膜型房颤患者华法林抗凝治疗后INR达标（INR 2.0~3.0）的比率分别为15.8%和7.1%。 结论为了达到更好的房颤患者卒中预防效果,需进一步加强华法林抗凝治疗的教育和监测。     

一项丹麦全国的随访研究:口服抗凝剂治疗在心房颤动射频消融术后远期血栓栓塞及严重出血事件的风险评估

<正>射频消融是目前治疗症状性心房颤动(房颤)的推荐手段,但目前还不确定射频消融是否可降低房颤所致血栓栓塞并发症的发生。欧洲心脏病学会(ESC)指南建议房颤射频消融术后至少接受3个月口服抗凝剂治疗,但3个月后是否继续服用需个体化评估卒中风险。一项丹麦全国的随访研究针对口服抗凝剂治疗在房颤射频消融术后血栓栓塞及严重出血风险进行了评     

成都地区房颤伴高血压患者卒中随访分析

目的调查成都地区2013~2015年非瓣膜性心房颤动(房颤)伴高血压患者1年后卒中发生情况,评估卒中发生的危险因素。方法随访1年,根据研究对象是否发生卒中分为卒中组和非卒中组,应用多因素logistic回归模型分析卒中发生的危险因素。结果入选495例房颤伴高血压患者,CHA2DS2-VASc≥2分466例,74例启用了抗凝治疗,抗凝治疗率14.9%,发生缺血性卒中45例,卒中发生率9.1%,多因素Logistic回归分析显示:在房颤伴高血压患者中年龄、女性、吸烟是1年缺血性卒中发生的独立危险因素,抗凝治疗是其保护因素。结论成都地区房颤伴高血压患者1年缺血性卒中发生率较高,抗凝治疗率低,抗凝治疗能降低缺血性卒中发生,年龄、女性、吸烟是缺血性卒中发生的危险因素。     

欧洲心脏节律协会关于非瓣膜病房颤患者新型口服抗凝剂使用的临床实践指南摘译

<正>新型口服抗凝剂(NOACs)作为维生素K拮抗剂(VKA)治疗的一种替代方法,用于非瓣膜病房颤患者血栓栓塞的预防。虽然在许多方面是非常有前途的(抗凝疗效可预测而无需监测,与食物和药物的相互作用更少,较短的血浆半衰期,以及良好的疗效安全性比),但正确使用NOACs在许多细节方面还需要新的探索。2010年欧洲心脏病学会     

关于脑出血后患者重启口服抗凝药的思考

脑出血后重启口服抗凝药(oral anticoagulant,OAC)是具有挑战性的话题.目前尚无高质量的随机对照试验能获知何时以何种方式重启OAC是安全的.最近几年一些重要研究认为,脑出血后重启OAC可降低栓塞事件的发生率和长期死亡率,且不明显增加出血风险;重启OAC在非脑叶出血患者比脑叶出血患者更安全;新型抗凝剂优于维生素K拮抗剂;建议高栓塞风险患者在脑出血后2周或更早重启OAC,非栓塞高风险患者在4～8周重启OAC,同时需考虑个体情况,严控血压.     

Edoxaban in Atrial Fibrillation and Venous Thromboembolism—Ten Key Questions and Answers: A Practical Guide

Edoxaban is the fourth non-vitamin K antagonist oral anticoagulant now available for clinical use in the prevention of stroke/systemic embolism in atrial fibrillation (AF) and in the treatment of venous thromboembolism (VTE), after the completion of large-scale randomized comparative clinical trials with the vitamin K antagonist warfarin. Edoxaban has some peculiar pharmacological properties and outcome data. Here a group of experts in AF and VTE answers a set of questions on its practical use, trying to define the profile of patients that would be most appropriate for its use.     

EMILIN2 (Elastin microfibril interface located protein), potential modifier of thrombosis

Warfarin has a long history of benefit and has become the gold standard medication for the prevention of ischemic stroke in patients with atrial fibrillation. Nevertheless, it is far from perfect and there is no doubt that new drugs must be found to replace warfarin. The new oral anticoagulants that are on the market or awaiting approval or under research offer some benefits but not enough to replace warfarin until results of additional studies can show an adequate balance between effectiveness/safety and cost/benefit. There are several issues concerning the new oral anticoagulants. It is essential that the effect of any anticoagulant can be measured in plasma. But to date, there is no test to assess the effect or therapeutic range for the new oral anticoagulants. There is no antidote to neutralize the action of the new drugs in cases of bleeding or when acute surgical intervention is necessary. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal failure. Rivaroxaban should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not yet been determined. How anticoagulant bridging can be done before surgery has not yet been established. In conclusion, although thousands of patients have been treated in phase III studies, additional data are necessary before conclusions can be drawn on the potential for these new anticoagulant drugs to replace warfarin in patients with atrial fibrillation.     

Non-Vitamin K Oral Anticoagulants for Stroke Prevention in Special Populations with Atrial Fibrillation

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events. These AF patients may be denied oral anticoagulants, whilst evidence shows that the absolute benefits of oral anticoagulants are greatest in patients at highest risk. NOACs are an alternative to VKAs to prevent stroke in patients with “non-valvular AF”, and NOACs may offer a greater net clinical benefit compared with VKAs, particularly in these high-risk patients. Physicians have to learn how to use these drugs optimally in specific settings. We review concrete clinical scenarios for which practical answers are currently proposed for use of NOACs based on available evidence for patients with kidney disease, elderly patients, women, patients with diabetes, patients with low or high body weight, and those with valve disease.     

Dabigatran for stroke prevention in atrial fibrillation: the RE-LY trial

Oral anticoagulation is the mainstay of therapy for stroke prevention in patients with atrial fibrillation. Vitamin K antagonists such as warfarin reduce the risk of cardioembolic stroke by approximately two-thirds compared with no treatment, but are limited by their unpredictable anticoagulant effect and narrow therapeutic index. Warfarin therapy requires routine coagulation monitoring, which is inconvenient for patients and costly for the healthcare system. The limitations of the vitamin K agonists have spurred the development of new oral anticoagulants that selectively inhibit thrombin or factor Xa. The Randomized Evaluation of Long-Term Anticoagulation (RE-LY) trial of 18,113 patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke demonstrated that dabigatran etexilate given at a dose of 150 mg twice daily compared with warfarin, reduced the rate of stroke or systemic embolism by one-third with a similar rate of major bleeding, whereas dabigatran etexilate given at a dose of 110 mg twice daily compared with warfarin had a similar rate of stroke or systemic embolism and reduced the rate of major bleeding by one-fifth. Both doses of dabigatran etexilate reduced intracranial bleeding by approximately two-thirds compared with warfarin. Based on the results of the RE-LY trial, both the US FDA and Health Canada recently approved dabigatran etexilate for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.     

The status and future directions of cardiac surgery

Oral anticoagulation is the mainstay of therapy for stroke prevention in patients with atrial fibrillation. Vitamin K antagonists such as warfarin reduce the risk of cardioembolic stroke by approximately two-thirds compared with no treatment, but are limited by their unpredictable anticoagulant effect and narrow therapeutic index. Warfarin therapy requires routine coagulation monitoring, which is inconvenient for patients and costly for the healthcare system. The limitations of the vitamin K agonists have spurred the development of new oral anticoagulants that selectively inhibit thrombin or factor Xa. The Randomized Evaluation of Long-Term Anticoagulation (RE-LY) trial of 18,113 patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke demonstrated that dabigatran etexilate given at a dose of 150 mg twice daily compared with warfarin, reduced the rate of stroke or systemic embolism by one-third with a similar rate of major bleeding, whereas dabigatran etexilate given at a dose of 110 mg twice daily compared with warfarin had a similar rate of stroke or systemic embolism and reduced the rate of major bleeding by one-fifth. Both doses of dabigatran etexilate reduced intracranial bleeding by approximately two-thirds compared with warfarin. Based on the results of the RE-LY trial, both the US FDA and Health Canada recently approved dabigatran etexilate for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.     

Combined antiplatelet and anticoagulant therapy: clinical benefits and risks

Summary.  The combination of anticoagulant and antiplatelet therapy is more effective than antiplatelet therapy alone for the initial and long-term management of acute coronary syndromes but increases the risk of bleeding. Antiplatelet therapy is often combined with oral anticoagulants in patients with an indication for warfarin therapy (e.g. atrial fibrillation) who also have an indication for antiplatelet therapy (e.g. coronary artery disease) but the appropriateness of such an approach is unresolved. Anticoagulation appears to be as effective as antiplatelet therapy for long-term management of acute coronary syndrome and stroke, and possibly peripheral artery disease, but causes more bleeding. Therefore, in such patients who develop atrial fibrillation, switching from antiplatelet therapy to anticoagulants might be all that is required. The combination of anticoagulant and antiplatelet therapy has only been proven to provide additional benefit over anticoagulants alone in patients with prosthetic heart valves. The combination of aspirin and clopidogrel is not as effective as oral anticoagulants in patients with atrial fibrillation, whereas the combination of aspirin and clopidogrel is more effective than oral anticoagulants in patients with coronary stents. Whether the benefits of triple therapy outweigh the risks in patients with atrial fibrillation and coronary stents requires evaluation in randomized trials.     

Phase III studies on novel oral anticoagulants for stroke prevention in atrial fibrillation: a look beyond the excellent results

Summary. In this overview we address the three phase III studies that compared new oral anticoagulants (dabigatran, rivaroxaban and apixaban) with warfarin in the setting of stroke prevention in atrial fibrillation. Strengths and weaknesses of the studies were examined in detail through indirect comparison. We analyze and comment the inclusion and exclusion criteria, the characteristics of randomized patients, the primary efficacy and safety end points and side effects. All new oral anticoagulants resulted in being non‐inferior to vitamin K antagonists in reducing stroke or systemic embolism in patients with atrial fibrillation. Dabigatran 150 mg and apixaban were superior to vitamin K antagonists. Importantly, new oral anticoagulants significantly reduced hemorrhagic stroke in all three studies. Major differences among new oral anticoagulants include the way they are eliminated and side effects. Both dabigatran and apixaban were tested in low‐ to moderate‐risk patients (mean CHADS2 [Congestive heart failure, Hypertension, Age, Diabetes, Stroke] score = 2.1–2.2) whereas rivaroxaban was tested in high‐risk patients (mean CHADS2 score = 3.48) and at variance with dabigatran and apixaban was administered once daily. Apixaban significantly reduced mortality from any cause. The choice of a new oral anticoagulant should take into account these and other differences between the new drugs.     

Apixaban for the prevention of stroke in atrial fibrillation

Until recently, pharmaceutical options for stroke prevention in atrial fibrillation were restricted to aspirin or vitamin K antagonist therapy. In recent years development has been underway for alternatives. Apixaban, a direct Factor Xa inhibitor, is orally dosed, target selective and has few known drug or food interactions. As such, it is a member of a new generation of anticoagulants expected to revolutionize the way we approach anticoagulation for stroke prevention in atrial fibrillation. Apixaban has been studied in Phase II and Phase III trials for a variety of indications. The AVERROES trial established apixaban as superior to aspirin for stroke reduction in patients with atrial fibrillation for whom vitamin K antagonist therapy is unsuitable. The recent ARISTOTLE trial found apixaban to be superior to warfarin for stroke prevention in a wide range of patients with atrial fibrillation, with significantly lower bleeding risk, and lower risk of all-cause mortality.     

Pharmacologic and nonpharmacologic therapies for stroke prevention in nonvalvular atrial fibrillation

Thromboembolism is the crucial cause of ischemic stroke in patients with atrial fibrillation (AF). Anticoagulation therapy with vitamin K antagonists, such as warfarin, have been proven to be effective for stroke prevention in AF. Nonetheless, the use of warfarin may be limited due to increased risk of bleeding, the potential interaction with multiple foods and drugs, and the need for routine coagulation monitoring. Over the last decade anticoagulants, such as dabigatran and rivaroxaban, have been developed and have shown superiority compared to warfarin for preventing stroke in patients with nonvalvular AF in large randomized trials. In addition, on account of the risk of thrombus formation in the left atrial appendage (LAA), many nonpharmacologic approaches have been developed to reduce stroke risk in patients with AF who are not candidates for anticoagulant therapy. Surgical, epicardial, and endovascular techniques for LAA closure are being investigated currently. Both novel pharmacotherapy and nonpharmacologic approaches for stroke prevention will be detailed in this review.     

Treatment options for multivessel coronary artery disease

Until recently, pharmaceutical options for stroke prevention in atrial fibrillation were restricted to aspirin or vitamin K antagonist therapy. In recent years development has been underway for alternatives. Apixaban, a direct Factor Xa inhibitor, is orally dosed, target selective and has few known drug or food interactions. As such, it is a member of a new generation of anticoagulants expected to revolutionize the way we approach anticoagulation for stroke prevention in atrial fibrillation. Apixaban has been studied in Phase II and Phase III trials for a variety of indications. The AVERROES trial established apixaban as superior to aspirin for stroke reduction in patients with atrial fibrillation for whom vitamin K antagonist therapy is unsuitable. The recent ARISTOTLE trial found apixaban to be superior to warfarin for stroke prevention in a wide range of patients with atrial fibrillation, with significantly lower bleeding risk, and lower risk of all-cause mortality.