Aspirin in stroke prevention in nonvalvular atrial fibrillation and stable vascular disease: an era of new anticoagulants

Atrial fibrillation (AF) is a major cause of ischemic stroke, especially in the elderly. There are currently enough data to support the notion that anticoagulation with warfarin or dabigatran is far superior to aspirin in the prevention of stroke or systemic embolism in AF. Aspirin is the preferred modality in patients who are either not candidates for anticoagulation, such as patients with increased risk for bleeding, low-risk patients based on the CHADS2 score or patients who have difficulty in maintaining a therapeutic international normalized ratio. There is no dispute on the recommendations regarding stroke prevention in high-risk patients (CHADS2 risk score of 2 and beyond) with AF. However, there is some controversy regarding the appropriate strategy (anticoagulation vs aspirin) for stroke prevention in low-risk patients (CHA2DS2-VASc score of 0-1). Novel oral anticoagulant drugs (direct thrombin inhibitors and Factor Xa inhibitors) might further diminish the role of aspirin for stroke prevention in AF due to their superior efficacy, lack of need for monitoring of therapeutic effects and lower bleeding risk when compared with warfarin, especially in patients with stable vascular disease.     

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。     

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.     

A review of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation

BACKGROUND: Warfarin therapy has proved safe and effective in a number of randomized controlled trials of stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF), reducing the risk of stroke in these patients by two thirds. However, participants in the clinical trials were carefully selected and younger than patients in actual clinical practice. OBJECTIVE: This analysis sought to determine whether the results of clinical trials in patients with NV can be extrapolated to the general population seen in clinical practice. METHODS: A MEDLINE search from 1966 to the present was used to identify observational trials of anticoagulation in patients with NVAF that addressed warfarin use, anticoagulation control, efficacy, and complications. The search terms used were atrial fibrillation and anticoagulation. RESULTS: Although warfarin prophylaxis against stroke in patients with NVAF appeared to be as well tolerated and effective in clinical practice as in clinical trials, it was generally underused, particularly in the elderly. Anticoagulation control was not as good in clinical practice as in clinical trials, although the rates of stroke and major bleeding were comparable. CONCLUSIONS: Judicious use of warfarin, tailored to individual stroke risk, seems to be a reasonable policy. Warfarin therapy increases quality-adjusted survival in patients at high risk for stroke, and it is recommended for medium-risk patients unless their risk of bleeding is high or their quality of life while taking warfarin would be poor. Patients at a low risk for stroke will have equivalent health outcomes and incur lower costs if treated with aspirin. Despite the increased risk of hemorrhage in elderly patients, the net benefit of warfarin therapy is greater in this age group because of the higher risk of stroke. Active involvement of patients and their caregivers in an anticoagulation service setting may improve outcomes of anticoagulation therapy.     

Value of pacemaker atrial diagnostic data in patients with paroxysmal atrial fibrillation: an opportunity to improve rates of warfarin utilization

Atrial diagnostic data within implantable devices provide an opportunity to assess the frequency and quantity of atrial fibrillation (AF) episodes (AF burden) and its impact on appropriate warfarin anticoagulation. Cardiologists were given clinical scenarios to review with different types of pacemaker diagnostic data in an elderly patient with risk factors for stroke. AF specific data was associated with increased warfarin utilization, but only at intermediate rates. Potential reasons and clinical implications are discussed.     

农村社区医师对房颤诊疗的认知现况调查

目的调查农村社区医师对心房颤动（房颤）疾病及其抗凝治疗的认识水平。 方法2015年对上海市松江区7家农村社区卫生服务中心的128名临床医师进行问卷调查,内容包括社区医师对房颤疾病的认识、社区医师对房颤抗凝治疗的认识、社区医师继续教育情况调查。分析被调查者目前对房颤的认知现状。 结果87.5%（112/128）的社区医师能正确回答房颤是一种心律失常。7.8%（10/128）的社区医师不了解房颤的心电图特征。82.8%（106/128）的社区医师选择中风是房颤的最常见的并发症。未能掌握房颤典型体征的社区医师占4.7%（6/128）。67.2%（86/128）的社区医师认为抗凝治疗对于大多数房颤患者是必不可少的。在房颤患者的首选抗凝药物上,43.8%（56/128）的社区医师认为是阿司匹林,52.5%（67/128）首选华法林和3.9%（5/128）首选氯吡格雷。12.5%（16/128）的社区医师能了解和熟练地使用房颤患者的脑卒中危险分层。7.8%（10/128）的社区医师能够很好地了解和正确评估抗凝血相关的出血风险。42.2%（54/128）的农村社区医师在近3年内没有接受房颤相关的医学继续教育,50.0%（64/128）的社区医师没有关注房颤诊疗指南的更新,65.6%（84/128）的社区医师未曾阅读过房颤诊疗指南,32.0%（41/128）的社区医师在过去的3年中没有接受任何心血管疾病相关的医学继续教育。 结论农村社区医师对于房颤抗凝治疗的认识存在严重不足,他们接受的房颤相关的医学继续教育也比较匮乏。     

Atrial fibrillation and stroke

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF is 0.4% in the general population and increases with age up to 6-8% in octogenarians. In Switzerland, approximately 68,000 persons are in atrial fibrillation, and in the EU countries 3.5 millions. Atrial fibrillation disturbs synchronous mechanical atrial activity and impairs the haemodynamics. This can give rise to thrombus formation, mostly in the left atrial appendage, and embolism to the systemic circulation. Clinical manifestations are most often neurological such as transient ischaemic attacks or ischaemic strokes, on average 5% per year. Of all strokes, one in every six occurs in patients with AF. Antiarrhythmic therapy is useful to improve cardiac rate and function in AF. However, to reduce first or recurrent emboli, antithrombotic therapy is of paramount importance. Adjusted-dose warfarin reduces first or recurrent strokes by about 60%. When patients with non-valvular AF are anticoagulated, the odds against ischaemic stroke and intracranial bleeding favour an INR between 2.0 and 3.0. Acetylsalicylic acid is less efficacious than warfarin in AF patients, reducing the risk of stroke by about 20%. Therefore, anticoagulation is the current treatment modality in AF patients at high or intermediate risk, i.e. patients with history of transient ischaemic attack or stroke, those aged > 65 years, those with a history of hypertension, diabetes, heart failure or structural heart disease, valvular disease or significant systolic dysfunction. Antiplatelet agents should be used only for young (< 65 years) AF patients at low risk.     

老年非瓣膜心房颤动及合并脑梗死住院患者抗栓治疗调查

目的探讨老年非瓣膜性心房颤动(NVAF)及合并脑梗死住院患者的临床特征、栓塞和出血风险及抗栓治疗现状。方法回顾分析583例非瓣膜老年心房颤动患者(≥60岁)的临床资料,分别应用CHADS2评分及CHA2DS2-VASc评分进行卒中风险分层,比较两种评分系统对卒中风险评估的差异,分析探讨各分层抗栓药物应用情况,并应用HAS-BLED评分进行出血风险评估。结果所有NVAF患者基础病中以高血压最常见占61.3%,其次冠心病占56.2%。583例NVAF心房颤动患者中,CHADS2评分≥2分351例,华法林用药率为2.6%,抗血小板用药率为82.3%,CHA2DS2-VASc评分≥2分522例,华法林用药率为2.1%,抗血小板用药率为84.7%。结论高血压和冠心病是大多数老年心房颤动患者的基础疾病,老年心房颤动及合并脑梗死患者应用华法林进行规范化抗凝治疗的比例低。     

Cost-effectiveness of genotype-guided warfarin therapy for anticoagulation in elderly patients with atrial fibrillation

Background: In patients with atrial fibrillation (AF), anticoagulation with warfarin decreases the risk of embolic stroke by >50%. Identification of genetic polymorphisms in enzymes involved in the metabolism of warfarin can partially predict the maintenance dose and thus potentially decrease the incidence of bleeding episodes secondary to warfarin overdose.Objectives: The objectives of this study were to evaluate the potential clinical and economic outcomes of genotype-guided warfarin therapy in elderly patients newly diagnosed with AF and to identify a threshold in bleeding risk at which such therapy may be cost-effective.Methods: A decision tree was designed to represent the medical decision (pharmacogenetic testing or not) and the main clinical outcomes (embolic stroke, bleeding). Event rates of embolic stroke and bleeding complications were based on data from previously published clinical trials and an observational study, respectively; costs were from a third-party payer perspective; and utilities were from the patient perspective. It was assumed that use of pharma-cogenetic testing would not lead the clinician to make any potentially harmful modifications to the regimen.Results: This analysis found that any reduction in major bleeding as a result of pharmacogenetic testing would lead to improved utility. The higher costs of pharmacogenetic testing compared with no testing would be immediately offset by any reduction in major bleeding.Conclusions: In this decision analysis, genotype-guided warfarin therapy for anticoagulation in elderly patients with AF was potentially cost-effective, and its benefits were closely related to efficacy in preventing bleeding events. Clinical trials testing the efficacy of genotype-guided warfarin therapy are warranted.     

经皮左心耳封堵的研究进展

心房颤动（房颤）在人群中的发病率逐年升高,成为临床中最常见的心律失常之一。脑栓塞是房颤最主要的并发症。抗凝治疗仍然是预防房颤脑卒中的主要手段,但无论是华法林还是新型抗凝药都有一定的局限性,存在相关的风险及禁忌,且依从性差。鉴于非瓣膜病性房颤患者90%以上的血栓来源于左心耳（LAA),故对于一些栓塞风险高的房颤患者,经皮左心耳封堵术已成为长期华法林替代治疗以降低新发脑卒中风险的另一选择。     

Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice

We conducted a retrospective cohort study of thromboprophylaxis rates and the quality of anticoagulation control among patients with atrial fibrillation (AF) using a large, geographically diverse database of electronic medical records. The study population consisted of 13,709 AF patients treated in US outpatient physician practices. Approximately two-thirds were prescribed warfarin alone or in combination with another drug. Older patients, males, and those with congestive heart failure (CHF) or prior stroke were more likely to receive antithrombotic therapy. Among 6454 patients treated with warfarin who had at least two valid prothrombin time/international normalised ratio test results, approximately half of study days were spent in target range. Female sex, CHF and residence in the Northeast were associated with more time out of range. Our study confirms that, in routine medical practice, warfarin is not prescribed for substantial numbers of eligible patients, and anticoagulation control with warfarin is suboptimal for many of those at risk for thromboembolism.     

超高龄心房颤动患者华法林抗凝过程中心血管不良事件的观察

目的: 观察超高龄房颤患者采用不同强度华法林抗凝后的心血管不良事件发生情况,探讨此类患者国际标准化比值(international normalized ratio,INR)的合理范围,为临床提供依据。方法: 将108例超高龄房颤患者（年龄≥80岁）按INR值分为中等强度抗凝组（56例）和低等强度抗凝组（52例）;低等强度抗凝组的INR维持在1.40~1.80;中等强度抗凝组的INR维持在1.81~2.50。随访（1.8±1.2）年,观察发生主要终点事件（缺血性卒中、全身性栓塞）、次要终点事件（非致命性心肌梗死、全因死亡联合终点）、安全性终点事件（致命性出血、严重出血和轻度出血）的情况。结果: 随访期间,中等强度抗凝组中有3例患者发生栓塞,发生率为5.36%;低等强度抗凝组中有6例发生栓塞,发生率为11.54%,均为脑卒中,2组间差异有统计学意义（P<0.05）。低等强度抗凝组中2例、中等强度抗凝组中3例患者出现眼结膜、鼻出血等不良反应,但均无严重出血,2组间出血发生率差异无统计学意义（P>0.05）。结论: 超高龄房颤患者应用华法林,INR维持在1.81~2.50是安全、有效的。     

Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation

The most severe consequence of atrial fibrillation (AF) is a cardioembolic stroke. The incidence of cardioembolic stroke increases significantly in patients with AF. Although warfarin has been the mainstay of the prevention of cardioembolic stroke, there are several limitations to the use of warfarin that hinder its effectiveness. This article provides the historical development of devices that exclude the left atrial appendage, their effectiveness and potential patient selection, as an alternative to warfarin and the novel oral anticoagulation therapy for the prevention of cardioembolic stroke in patients with AF.     

Atrial Fibrillation and Anticoagulation in Patients with Permanent Pacemakers: Implications for Stroke Prevention

Several large prospective randomized trials have demonstrated that anticoagulation with warfarin reduces the risk of thromboembolic stroke in high risk patients with chronic AF by approximately 70%. Large numbers of patients with permanent pacemakers have AF, and anticoagulation rates in this population have not been described. In a prospective analysis of 110 consecutive patients attending the pacemaker clinic of a large university hospital, we assessed the number of patients with AF and the proportion of these patients who were receiving anticoagulation to prevent thromboembolic stroke. Where necessary, temporary pacemaker reprogramming to low ventricular rates was utilized to facilitate the diagnosis of AF. Fifty-three of the 110 patients (48%) were diagnosed with AF, all of whom (100%) had accepted high risk factors for thromboembolic stroke. Only eight of the 53 (15%) had been anticoagulated with warfarin. Thirty-six of the 53 patients (68%) diagnosed with AF had no prior documented diagnosis of chronic AF, and the majority had no symptoms suggesting AF. A single lead II ECG was insufficient in 67 of the 110 patients (61%) to diagnose the underlying atrial rhythm; the remainder required 12-lead ECGs or temporary pacemaker reprogramming to low ventricular rates to diagnose the underlying atrial rhythm. AF is common in patients with permanent pacemakers. It is commonly asymptomatic, and anticoagulation is markedly underutilized in reducing stroke risk in these patients. Attention to the possibility of AF in paced patients should allow prompt diagnosis and allow both the initiation of anticoagulation in order to reduce thromboembolic stroke risk and consideration for cardioversion of AF to sinus rhythm.     

The impact of comorbidities on stroke prophylaxis strategies in atrial fibrillation patients

Arial fibrillation (AF) is the most commonly occurring sustained arrhythmia in the United States and is associated with increased mortality. AF is a risk factor for ischemic stroke, and risk factors for AF include comorbid conditions such as congestive heart failure, diabetes mellitus, older age, hypertension, diabetes, pulmonary disease, and history of stroke, transient ischemic attack, or heart failure. Risk stratification for ischemic stroke in AF patients is based on scoring a group of risk factors that allows for the appropriate tailoring of antithrombotic therapy. The vitamin K antagonists are effective at reducing ischemic stroke rates in medium-risk to high-risk patients and are therefore generally recommended for this group. However, a large proportion of these patients are not treated with vitamin K antagonists because of the potential for adverse outcomes, particularly in elderly patients. New direct thrombin inhibitors and direct Factor Xa inhibitors in development offer the possibility of simplifying treatment and management although offering similar or better efficacy and safety profiles to warfarin. In light of these potential new treatments, the importance and improvement of risk stratification methods and the resulting recommendations in thromboprophylaxis become even more paramount as they make it more likely that medium-risk to high-risk patients can be treated safely.     

Anticoagulation in elective surgery.

Several categories of patients may be receiving anticoagulation therapy and require surgery. Many patients take cardioprotective aspirin or warfarin for atrial fibrillation, the presence of a mechanical heart valve, prior thromboembolism, a documented left ventricular thrombus, or a history of venous thromboembolism with or without a pulmonary embolism. Inpatients may be receiving injectable forms of anticoagulation to reduce risk of deep venous thrombosis or for other conditions, such as atrial fibrillation. Patients receiving any type of anticoagulation present a problem when they require surgery because the interruption of anticoagulant therapy increases their risk of thromboembolism and stroke (Schanbacher & Bennett, 2000). Rational decisions regarding the appropriateness of perioperative anticoagulation depend on individual patient factors and can only be made when the risk of perioperative thromboembolism is balanced against the risk of perioperative bleeding.     

ATRIAL FIBRILLATION IN A GENERAL HOSPITAL: HOW WELL ARE WE DOING?

Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and anticoagulation is now indicated in many patients, particularly those with congestive cardiac failure, hypertension, a history of transient ischaemic attacks or embolic stroke. In a retrospective study (and audit), we examined 280 cases of AF (acute, paroxysmal non-sustained and chronic sustained) admitted to a general hospital in the UK. The commonest underlying medical condition was ischaemic heart disease (57%), while the commonest presenting feature was congestive cardiac failure (60%). Pharmacological cardioversion was preferred against electrical cardioversion for reverting to sinus rhythm. Fifty-six patients (20%) received warfarin, 55 patients (20%) were on aspirin, and the remaining 169 (60%) received neither warfarin nor aspirin. More awareness is needed among physicians managing AF particularly in relation to anticoagulation.     

Anticoagulation for stroke prevention in elderly patients with atrial fibrillation,including those with falls and/or early-stage dementia: A single-center,retrospective, observational study

Background: Anticoagulation for stroke prevention is underused in elderly patients with nonvalvular atrial fibrillation (AF). Those with falls and/or early dementia may be at particular risk for stroke and hemorrhage.Objective: The aim of this study was to determine the prescribing patterns, risks, and benefits of anticoagulation with warfarin or acetylsalicylic acid (ASA) in elderly patients with AF at risk for stroke and hemorrhage, including those with falls and/or dementia.Methods: In this single-center, retrospective, observational study, data from patients aged ≥65 years with chronic nonvalvular AF treated at an urban academic geriatrics practice over a 1-year period were included. Eligible patients were receiving noninvasive management of AF with warfarin or ASA. Data were assessed to determine the prevalences of stroke, hemorrhage, falls, and the possible effects of anticoagulation with dementia. Outcomes events at 12 months, including time-in-therapeutic range (TTR), stroke, hemorrhage, and death, were determined. The stroke risk in each patient was estimated using the CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes, history of stroke or transient ischemic attack) score, and the risk for hemorrhage was estimated using the Outpatient Bleeding Risk Index.Results: A total of 112 patients (mean age, 82 years) were identified; 106 were included in the present analysis (80 women, 26 men); 6 were not receiving antithrombotic therapy and thus were excluded from the analysis. Warfarin was prescribed in 85% (90 patients); ASA, 15% (16). International normalized ratio testing was done frequently, with a median interval of 13.7 days between tests (92% within 28 days). No association was found between an improved TTR and the number of tests per unit of time or the number of patients per clinician. The distributions of both the CHADS₂ and Outpatient Bleeding Risk Index scores were not significantly different between the warfarin and ASA groups. The proportions of patients treated with warfarin were not significantly different between the groups with a high risk for hemorrhage and the groups at lower risk. At 12 months in the 90 patients initially treated with warfarin, the rate of stroke was 2% (2 patients); major hemorrhage, 6% (5); and death, 20% (18). Mortality was greater in patients with falls (45% [5/11]) and/or dementia (47% [8/17]) compared with those without either falls or dementia (12% [8/65]).Conclusions: In this well-monitored geriatric population with chronic AF, including patients with falls and/or dementia, a high percentage were prescribed warfarin (85%), with low rates of stroke, hemorrhage, and death at 12 months despite a low TTR. Patients with falls and/or dementia had a high mortality rate (~45%).