Underutilization of anticoagulation therapy in chronic atrial fibrillation

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.     

左心耳形态结构和功能与心房颤动相关性脑卒中的研究和展望

心房颤动（简称房颤）是临床最常见的持续性心律失常,房颤患者缺血性脑卒中的风险较非房颤患者明显增高,而其血栓主要来源于左心耳（LAA）。长期以来,非瓣膜性房颤患者的抗凝原则主要依据CHA2DS2-VASC评分,但是对于中低危患者存在局限性。随着医学影像学的发展,学者们发现左心耳形态结构特征和功能参数与血栓形成有关,可潜在地用于预测房颤脑卒中的发生。故本文拟对此进行综述,以期为下一步研究提供思路。     

Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention

Atrial fibrillation is associated with a sixfold increased risk for stroke. More than a dozen published randomized trials of anticoagulants or antiplatelet agents for stroke prevention provide solid evidence on which to base antithrombotic prophylaxis. Adjusted-dose warfarin reduces risk for stroke by about 60% compared with placebo, aspirin reduces this risk (primarily for nondisabling stroke) by about 20% compared with placebo, and warfarin reduces it by about 40% compared with aspirin. Warfarin provides maximal protection against stroke at international normalized ratios of 2.0 to 3.0. Risk stratification of patients with atrial fibrillation identifies those who potentially benefit most or least from anticoagulation; this is important because a substantial percentage of patients with atrial fibrillation have relatively low rates of stroke if they are given aspirin. Many elderly patients with recurrent intermittent atrial fibrillation experience high rates of stroke and benefit from anticoagulation. The value of precordial or transesophageal echocardiography in addition to clinical risk stratifiers for stratifying stroke risk is controversial. Altered hemostasis favoring thrombosis may contribute to formation of atrial appendage thrombus, but these conditions remain ill defined. The past decade has brought unprecedented progress toward understanding thromboembolism in patients with atrial fibrillation and has changed the clinical perspective of a prevalent cardiac arrhythmia into an important opportunity for stroke prevention. Making the most of this promise calls for appreciation of the epidemiology of atrial fibrillation and the concept of risk specificity in the face of diverse therapeutic options.     

中国人非瓣膜性心房颤动脑卒中危险因素的病例-对照研究

目的　本研究通过回顾性病例对照研究分析中国人心房颤动 (房颤 )脑卒中的危险因素。方法　在全国 1 8家医院共登记房颤患者 4 51 1例 ,其中风湿瓣膜性房颤 1 0 86例 ,非瓣膜性房颤 342 5例。通过比较房颤合并脑卒中与房颤无脑卒中患者 ,筛选房颤发生脑卒中的危险因素。结果　中国人房颤脑卒中的患病率 2 4 81 % ,房颤合并脑卒中组年龄明显高于对照组 (P <0 0 0 1 ) ,且患病率随年龄增长而明显增加。多因素Logistic分析显示 :年龄≥ 75岁 (OR 1 76 ,95 %CI 1 0 8～ 2 98) ,高血压病史 (OR 1 52 ;95 %CI 1 2 8～ 1 80 ) ,糖尿病史 (OR 1 39,95 %CI 1 1 1～ 1 76) ,动脉收缩压升高(OR 1 71 ,95 %CI1 2 1～ 2 2 8) ,左房血栓 (OR 2 77,95 %CI 1 2 5～ 6 1 3)是脑卒中的独立危险因素。结论　中国人非瓣膜性房颤脑卒中的独立危险因素为年龄、高血压病史、糖尿病史、左房血栓、动脉收缩压升高 ,上述因素对决定房颤患者的抗栓治疗策略具有重要意义     

Prior History of Falls and Risk of Outcomes in Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

BackgroundPatients with nonvalvular atrial fibrillation are often denied oral anticoagulation due to falls risk. The latter is variably defined, and existing studies have not compared the associated risk of bleeding with other cardiovascular events. There are no data about outcomes in individuals with nonvalvular atrial fibrillation with a prior history of (actual) falls, rather than being “at risk of falls.” Our objective was to evaluate the risk of cardiovascular outcomes associated with prior history of falls in patients with atrial fibrillation in a contemporary “real world” cohort.MethodsPatients with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were included. Stroke/thromboembolism event rates were calculated according to prior history of falls. Risk factors were investigated by Cox regression.ResultsAmong 7156 atrial fibrillation patients, prior history of falls/trauma was uncommon (n = 76; 1.1%). Compared with patients without history of falls, those patients were older and less likely to be on oral anticoagulation; they also had higher risk scores for stroke/thromboembolism but not for bleeding. Compared with no prior history of falls, rates of stroke/thromboembolism (P = .01) and all-cause mortality (P < .0001) were significantly higher in patients with previous falls. In multivariable analyses, prior history of falls was independently associated with stroke/thromboembolism (hazard ratio [HR] 5.19; 95% confidence interval [CI], 2.1-12.6; P < .0001), major bleeding (HR 3.32 [1.23-8.91]; P = .02), and all-cause mortality (HR 3.69; 95% CI, 1.52-8.95; P = .04), but not hemorrhagic stroke (HR 4.20; 95% CI, 0.58-30.48; P = .16) in patients on oral anticoagulation.ConclusionIn this large “real world” atrial fibrillation cohort, prior history of falls was uncommon but independently increased risk of stroke/thromboembolism, bleeding, and mortality, but not hemorrhagic stroke in the presence of anticoagulation. Prior history of (actual) falls may be a more clinically useful risk prognosticator than “being at risk of falls.”     

左心耳封堵策略选择

心房颤动是临床上最常见的心律失常之一,血栓栓塞并发症是其致残、致死的主要原因。经食管超声检查发现,非瓣膜性房颤患者心房内血栓90%位于左心耳。因此,预防左心耳血栓形成可能会减少血栓栓塞事件的发生。口服抗凝药是预防房颤血栓栓塞并发症的有效方法,但是很多患者不能耐受口服抗凝药药物治疗。随着心血管介入治疗和器械研发的进展,经皮左心耳封堵预防卒中越来越受到关注,已经成为一种替代华法林预防房颤并发卒中的有效方法。     

Evidence-based percutaneous closure of the left atrial appendage in patients with atrial fibrillation

Atrial fibrillation is the most common cardiac arrhythmia, and its prevalence is increasing. Cardioembolic stroke, most of the times secondary to thrombus formation in the left atrial appendage, is its most feared and life threatening consequence. Oral anticoagulation with vitamin-K-antagonists is currently the most used prophylaxis for stroke in patients with atrial fibrillation; unfortunately, its benefits are limited by a narrow therapeutic window and an increased risk for bleeding, making it often undesired. Percutaneous occlusion of the left atrial appendage is a novel alternative strategy for cardioembolic stroke prophylaxis in patients with atrial fibrillation at a high risk of stroke but with contraindication for long-term oral anticoagulation therapy. At present, several devices have been developed specifically for percutaneous occlusion of the left atrial appendage. Current results show good feasibility and efficacy for these devices, with a high rate of successful implantation, although also associated with the inherent potential periprocedural complications. This work reviews the current state of the art of percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation.     

Der katheterbasierte Verschluss des linken Vorhofohrs

In patients with nonvalvular atrial fibrillation, >90?% of thrombi are detected in the left atrial appendage (LAA). In particular these observations have resulted in the development of catheter-based LAA closure as an approach for stroke prevention in patients with nonvalvular atrial fibrillation in recent years. A preliminary randomized trial provided promising data with respect to efficacy and safety of this approach as compared to anticoagulation with warfarin. The safety of the procedure has been significantly improved in recent years due to procedural experience and refinement of implanted devices. In current clinical practice, this approach is particularly used for patients with nonvalvular atrial fibrillation, a significant ischemic risk (CHA₂DS₂-VASc score ≥2), and a high bleeding risk, i.?e., in patients in whom there are relevant concerns with respect to long-term anticoagulation. The present article discusses the data from randomized clinical studies and registries, the present guideline recommendations, and the practical clinical use of LAA closure for stroke prevention.     

Prevention of embolic strokes: the role of the American College of Chest Physicians

Patients with atrial fibrillation (AF) face an annual stroke risk of about 5%. Evidence that anticoagulants reduce the risk of stroke has evolved over the 20th century. The American College of Chest Physicians (ACCP) has played a critical role in presenting guidelines for stroke prevention in AF. This commentary highlights the role that the ACCP guidelines have played, from their inception to the ninth edition. The first ACCP Conference on Antithrombotic and Thrombolytic Therapy in 1986 developed evidence-based guidelines for the indications, dosage, and monitoring of antithrombotic therapy. The conference recommended that anticoagulants be monitored by the international normalized ratio, and the appropriate dosage was to increase the international normalized ratio to two to three times control. This recommendation was widely accepted. Anticoagulants were recommended for AF with mitral valve disease and for nonvalvular AF with a history of embolism. No recommendations were made for nonvalvular AF without a history of embolism. These recommendations stimulated numerous randomized controlled trials (RCTs). By the third ACCP conference in 1992, RCTs had demonstrated a dramatic 69% stroke reduction in patients with nonvalvular AF. The third ACCP conference was the first to strongly recommend anticoagulation for primary and secondary stroke prevention in nonvalvular AF. ACCP conferences since 1992 have refined recommendations for nonvalvular AF on the basis of associated risk factors. The most recent conference, in 2011, recommended a direct thrombin inhibitor, dabigatran, rather than warfarin as the anticoagulant of choice. These ACCP guidelines have played a critical role in changing physicians' practice patterns. In 1980 only 7% of patients with AF in the United States received OA; by 2007, this had increased to 57%.     

Rivaroxaban for stroke prevention in atrial fibrillation and secondary prevention in patients with a recent acute coronary syndrome

The occurrence of disabling stroke, the major fatal consequence of atrial fibrillation, can be reduced by almost two-thirds with warfarin oral anticoagulation. Recent estimates on the prevalence of atrial fibrillation in the USA suggest that approximately 3 million people suffer from this common cardiac arrhythmia, therefore, the socioeconomic impact of adequate oral anticoagulation is enormous. Rivaroxaban, a direct orally available factor Xa inhibitor, is the first of a new class of drugs that target a central factor of the coagulation cascade upstream of thrombin. In the ROCKET AF clinical trial, rivaroxaban demonstrated noninferiority compared with warfarin for stroke prevention in patients with atrial fibrillation, while intracranial and fatal bleeding occurred less frequently with rivaroxaban treatment. Rivaroxban has recently been approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation by the US FDA and EMA. Very recently, rivaroxaban in addition to dual antiplatelet therapy, was shown to reduce mortality in patients with a recent acute coronary syndrome in the ATLAS ACS 2-TIMI 51 clinical trial. The clinical evaluation of rivaroxaban in cardiovascular disease and the results of the ROCKET AF study, the landmark clinical trial of rivaroxaban for stroke prevention, are discussed along with the unique pharmacological profile of rivaroxaban.     

Prognostic implications of left artial spontaneous echo contrast in nonvalvular atrial fibrillation

Objectives. This study examined the influence of left atrial spontaneous echo contrast on the subsequent stroke or embolic event rate and on survival in patients with nonvalvular atrial fibrillation.Background. Left atrial spontaneous echo contrast is associated with atrial fibrillation and a history of previous stroke or other embolic events. However, the prognostic implications of spontaneous contrast in patients with nonvalvular atrial fibrillation are unknown.Method. The study group comprised 272 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography. Clinical and echocardiographic data were collected at baseline, and patients were prospectively followed up, and all strokes, other embolic events and deaths were documented. The relation between spontaneous contrast at baseline and subsequent stroke, other embolic events and survival was analyzed.Results. Left atrial spontaneous echo contrast was detected at baseline in 161 patients (59%). The mean follow-up was 17.5 months. The stroke or other embolic event rate was 12%/year (15 strokes, 3 transient ischemic attacks, 2 peripheral embolisms) in patients with, compared with 3%/year (5 strokes) in patients without, baseline spontaneous contrast (p = 0.002). In 149 patients without previous thromboembolism, the event rate was 9.5%/year in patients with and 2.2%/year in patients without spontaneous contrast (p = 0.003). There were 25 deaths in patients with and 11 deaths in patients without spontaneous contrast. Patients with spontaneous contrast had significantly reduced survival (p = 0.025). On multivariate analysis, spontaneous contrast was the only positive predictor (odds ratio 3.5, p = 0.03) and warfarin therapy on follow-up the only negative predictor (odds ratio 0.23, p = 0.02) of subsequent stroke or other embolic events.Conclusions. Transesophageal echocardiography can riskstratify patients with nonvalvular atrial fibrillation by identifying left atrial spontaneous echo contrast. These patients have both a significantly higher risk of developing stroke or other embolic events and a reduced survival, and they may represent a subgroup in whom the risk/benefit ratio of anticoagulation may be most favorable.     

Antikoagulation bei Vorhofflimmern

Atrial fibrillation is associated with a relevant risk for ischemic stroke: Observational studies suggest that one in four to five strokes is due to atrial fibrillation. Depending on the risk profile of an individual patient, the yearly risk for a stroke is between 2% and 14%. Continuous oral anticoagulation is indicated if atrial fibrillation is accompanied by at least one additional risk factor for thromboembolic complications. This recommendation is supported by several large randomized trials. Due to their low therapeutic range, vitamin K antagonists (phenprocoumon, warfarin, and others), the most commonly used oral anticoagulants, require regular anticoagulation monitoring. If well-controlled (international normalized ratio 2-3, in elderly patients preferably 2-2.5), oral anticoagulation prevents more than half of ischemic strokes related to atrial fibrillation, while bleeding complications are rare. In the follow-up of low risk patients (CHADS2-Score 0), oral anticoagulation becomes necessary when risk factors for thromboembolic complications develop. If a stroke occurs during oral anticoagulation and an INR>2 in a patient with atrial fibrillation, other causes than thromboembolic events should be considered. New anticoagulants--especially direct thrombin antagonists--are currently evaluated in clinical trials and may in the future facilitate anticoagulation in patients with atrial fibrillation.     

Antithrombotic therapy in atrial fibrillation with ximelagatran: can it be an alternative to warfarin?]

Nonvalvular atrial fibrillation is the most common cardiac arrhythmia associated with a substantial risk of thromboembolism and stroke. Despite numerous disadvantages that limit its efficacy and safety, warfarin is widely used in the prevention and treatment of thromboembolism related with atrial fibrillation. Ximelagatran, an oral direct thrombin inhibitor has the potential to be an alternative choice in the prevention and therapy of thromboembolism related with atrial fibrillation. Studies compared ximelagatran with warfarin in nonvalvular atrial fibrillation at risk for stroke showed that fixed dose oral ximelagatran is effective as adjusted dose warfarin in stroke prevention. Ximelagatran has numerous advantages over warfarin in clinical practice. Although it seems as a promising option for the prevention and therapy of thromboembolism, its safety and efficacy need to be determined definitely by further clinical trials.     

Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study

BACKGROUND: Warfarin dramatically reduces the risk for ischemic stroke in nonvalvular atrial fibrillation, but its use among ambulatory patients with atrial fibrillation has not been widely studied. OBJECTIVE: To assess the rates and predictors of warfarin use in ambulatory patients with nonvalvular atrial fibrillation. DESIGN: Cross-sectional study. SETTING: Large health maintenance organization. PATIENTS: 13428 patients with a confirmed ambulatory diagnosis of nonvalvular atrial fibrillation and known warfarin status between 1 July 1996 and 31 December 1997. MEASUREMENTS: Data from automated pharmacy, laboratory, and clinical-administrative databases were used to determine the prevalence and determinants of warfarin use in the 3 months before or after the identified diagnosis of atrial fibrillation. RESULTS: Of 11082 patients with nonvalvular atrial fibrillation and no known contraindications, 55% received warfarin. Warfarin use was substantially lower in patients who were younger than 55 years of age (44.3%) and those who were 85 years of age or older (35.4%). Only 59.3% of patients with one or more risk factors for stroke and no contraindications were receiving warfarin. Among a subset of "ideal" candidates to receive warfarin (persons 65 to 74 years of age who had no contraindications and had previous stroke, hypertension, or both), 62.1% had evidence of warfarin use. Among our entire cohort, the strongest predictors of receiving warfarin were previous stroke (adjusted odds ratio, 2.55 [95% CI, 2.23 to 2.92]), heart failure (odds ratio, 1.63 [CI, 1.51 to 1.77]), previous intracranial hemorrhage (odds ratio, 0.33 [CI, 0.21 to 0.52]), age 85 years or older (odds ratio, 0.35 [CI, 0.31 to 0.40]), and previous gastrointestinal hemorrhage (odds ratio, 0.47 [CI, 0.40 to 0.57]). CONCLUSIONS: In a large, contemporary cohort of ambulatory patients with atrial fibrillation who received care within a health maintenance organization, warfarin use was considerably higher than in other reported studies. Although the reasons why physicians did not prescribe warfarin could not be elucidated, many apparently eligible patients with atrial fibrillation and at least one additional risk factor for stroke, especially hypertension, did not receive anticoagulation. Interventions are needed to increase the use of warfarin for stroke prevention among appropriate candidates.     

Stroke prevention in nonvalvular atrial fibrillation.

There has been considerable uncertainty about the best way to prevent stroke in patients with nonvalvular atrial fibrillation. Recent studies have suggested that low-dose warfarin therapy, in addition to producing fewer bleeding complications, may be as effective as higher-dose therapy in preventing thromboembolic events. Four large, prospective, randomized trials have examined the risks and benefits of warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation. All four studies showed a substantially reduced incidence of stroke and a low incidence of significant bleeding in patients treated with warfarin. One of these studies also showed that aspirin reduced the incidence of stroke. The benefits associated with long-term low-dose warfarin therapy appear to exceed the risks for serious bleeding in most patients with atrial fibrillation. Aspirin may be a viable therapeutic option for patients who are unable to take warfarin or for those in subgroups at a low risk for stroke.     

心房颤动和认知功能下降的关系研究

心房颤动(房颤)是老年人常见的心律失常,并随着年龄增长发病率及病死率增高.众多的血管危险因素和血管疾病导致认知功能障碍和痴呆,而年龄亦是认知功能障碍的最主要因素.房颤和认知功能障碍相关的可能机制有:共同危险因素及共患病、缺血性卒中(有症状或无症状)和房颤的促炎状态等.房颤患者窦律的恢复和抗凝治疗有可能降低认知功能障碍的...     

Anticoagulación oral en la fibrilación auricular no valvular: ¿son efectivas y seguras las recomendaciones científicas en la práctica clínica diaria?

INTRODUCTION AND OBJECTIVES: To study the efficacy and safety of an oral anticoagulation protocol for the treatment of nonvalvular atrial fibrillation, based on scientific associations' recommendations, in unselected patients seen in daily clinical practice. METHODS: The study included all consecutive patients with permanent nonvalvular atrial fibrillation who attended two outpatient cardiology clinics between February 1, 2000 and February 1, 2002. They were treated according to an anticoagulation protocol based on Spanish Society of Cardiology and American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. Patients were followed up prospectively for major events, such as death, stroke, transient ischemic attack, peripheral embolism and severe hemorrhage, which were recorded by treatment group. RESULTS: A total of 624 patients were included in the study. Those receiving anticoagulation therapy (n=425; 68%) more frequently had hypertension, diabetes and previous embolism as well as a greater number of cardioembolic risk factors (P< .001). Overall, 93% of non-anticoagulated patients received platelet aggregation inhibitors (92% received aspirin). After a median follow-up of 21 months, the probability of an embolic event was lower in anticoagulated patients (0.81% vs 14.04%; P< .001), as was all-cause mortality (3.27% vs 6.42%; P=.003). However, there was no significant difference in the probability of severe bleeding (2.75% vs 2.93%; P=.96). Results were unchanged after adjustment for age, sex, and previous embolic events. CONCLUSIONS: Oral anticoagulation therapy for nonvalvular atrial fibrillation implemented according to scientific associations' recommendations is effective and safe in daily clinical practice.     

Transesophageal echocardiography risk factors for stroke in nonvalvular atrial fibrillation

Atrial fibrillation is a common arrhythmia, particularly in the older age groups. It confers an increased risk of thromboembolism to these patients, and multiple clinical risk factors have been identified to be useful in predicting the risks of thromboembolic events. Recent studies have evaluated the role of transesophageal echocardiography (TEE) in the evaluation of patients with atrial fibrillation. The purpose of this review is to evaluate the significance of transesophageal echocardiographic findings in the prediction of thromboembolic events, particularly stroke, in patients with nonvalvular atrial fibrillation, with an emphasis on recently reported prospective studies. Aortic plaque and left atrial appendage abnormalities are identified as independent predictors of thromboembolic events. Although they are associated with clinical events, they also have independent incremental prognostic values. Other transesophageal echocardiographic findings, such as patent foramen ovale and atrial septal aneurysm, have not been found to be predictors of thromboembolic events in this patient group. Thus, TEE is a useful tool in stratifying patients with nonvalvular atrial fibrillation into different risk groups in terms of thromboembolic events, and it will likely play an important role in future studies to assess new treatment strategies in high-risk patients with atrial fibrillation.     

Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation

We performed unenhanced computed tomographic scans on 141 asymptomatic patients with nonvalvular atrial fibrillation. Thirty-six patients (26%) had hypodense areas consistent with cerebral infarction. The majority of these were small deep infarcts, seen in 29 patients (21%), but 13 patients (9%) had cortical or large deep infarctions. Twelve patients had more than one infarct on computed tomographic scan. Increasing age and increased left atrial diameter were the only clinical features associated with asymptomatic infarction. Patients older than 65 years with a left atrial diameter greater than 5.0 cm (n = 23) had a 52% prevalence of asymptomatic infarction. Patients younger than 65 years with a left atrial diameter less than 5.0 cm (n = 38) had an 11% prevalence of silent infarction. Patients with only one of these risk factors (n = 72) had a 24% prevalence of silent infarction. Infarction was more common in those with chronic (34%) as opposed to intermittent (22%) nonvalvular atrial fibrillation, but this difference was not significant. Hypertension, diabetes, duration of atrial fibrillation, congestive heart failure, history of myocardial infarction, and echocardiographic evidence of left ventricular dysfunction were not associated with asymptomatic infarction. A history of hypertension was present in only 35% of our patients with small-deep asymptomatic infarction, similar to the percentage in patients without stroke. Asymptomatic cerebral infarction is common in nonvalvular atrial fibrillation. The association with enlarged left atria and the lack of correlation with major cerebrovascular risk factors suggests a cardioembolic mechanism. Further study is needed to determine the functional and prognostic significance of these strokes.