New developments in anticoagulation therapy for Ione atrial fibrillation

Lone atrial fibrillation is a major health problem for elderly patients with cardiovascular risk factors as hypertension, congestive heart failure or previous myocardial infarction. The increased stroke rate of these patients is significantly reduced by oral anticoagulation (target: INR 2-3) and less effective by acetylsalicylic acid at a dose of 325 mg/d. As an alternative to the vitamin K-antagonistic anticoagulants currently the SPORTIF trial program is performed investigating the safety and efficacy of the oral direct thrombin inhibitor ximelagatran. Recent data derived from a dose-finding study and its open label continuous follow-up period are very encouraging with regard to the low incidence of bleeding complications and ximelagatran's clinical efficacy for the prevention of thromboembolic events. Large confirmatory trials engaging about 3000 patients each are under way in Europe as an open-label trial and the United Staates as a double blind trial. Results are being expected for the end of year 2002. These data will clarify the role of ximelagatran for the prevention of thromboembolic events in patients with lone atrial fibrillation and may give us an insight into a new standard drug regimen for stroke prevention in high risk patients.     

Managing anticoagulation in patients with atrial fibrillation

Patients with nonvalvular atrial fibrillation have an increased risk of cerebral thromboembolism. Oral anticoagulation therapy, however, provides primary and secondary stroke prevention in these patients. Here, update your knowledge of warfarin initiation, titration, monitoring, and adjustment.     

Underuse of anticoagulation in patients with atrial fibrillation

Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Guidelines recommend anticoagulation for patients with intermediate and high stroke risk (CHA₂DS₂-VASc score ≥2). Underuse of anticoagulants among eligible patients remains a persistent problem. Evidence demonstrates that the psychology of the fear of causing harm (omission bias) results in physicians’ hesitancy to initiate anticoagulation and an inaccurate estimation of stroke risk. The American Heart Association (AHA) initiated the Get With The Guidelines-AFIB (GWTG-AFIB) module in June 2013 to enhance guideline adherence for treatment and management of AF. Better quality of care for AF patients can be provided by increasing adherence to anticoagulation guidelines and improving patient compliance with anticoagulation therapy through education and established protocols. Nonvitamin K antagonist oral anticoagulants may facilitate better patient adherence due to ease of administration and reduced monitoring burden. In this review, we discuss the reasons for underuse, omission bias contributing to underuse, and different strategies to address this issue.     

Antiarrhythmic drugs for atrial fibrillation: focus on dronedarone

Patients with atrial fibrillation have an increased risk of stroke and heart failure, as well as impairment of their quality of life. Most trials have primarily focused on the prevention of stroke and heart failure, and the improvement of symptoms in these patients. More recently, a rate-control strategy has been reported to be a noninferior strategy compared with a rhythm-control strategy in atrial fibrillation patients. Many different classes of antiarrhythmic drugs have been used for rhythm control, with inconsistent results and adverse effects on mortality and morbidity. Of the available antiarrhythmic drugs, amiodarone is the single most effective drug in the prevention of atrial fibrillation recurrences and maintaining sinus rhythm; however, it is vastly limited by its various systemic side effects, especially those observed with long-term use. However, recent trial data from a new antiarrhythmic agent, dronedarone, suggest that this drug may be a safe alternative to amiodarone; however, its long-term efficacy and safety still require exploration.     

心房颤动抗凝治疗的现状与新进展

心房颤动(房颤)是缺血性脑卒中的一项重要独立危险因素,房颤患者一旦发生缺血性脑卒中,对其预后往往造成严重的不良后果。故房颤患者积极抗凝,预防缺血性卒中是治疗的一个重要环节。近年来,应对预防脑卒中的风险评估、抗凝治疗的强度及药物的选择都涌现出不少研究热点和新的认识。本文对此作一综述。     

Pharmacoeconomics of anticoagulation therapy for stroke prevention in atrial fibrillation: a review

INTRODUCTION: Atrial fibrillation (AF) increases the risk of ischemic stroke 5-fold and may not only be responsible for as many as 15% of all strokes that occur but also for larger and more disabling strokes than those attributable to other causes which increase the associated costs of care. Anticoagulation with warfarin in the target INR of 2.5 is a major clinical challenge in real-life practice, given that the complex relationship between warfarin dosage and response is readily altered by a variety of factors such as concurrent medications, illnesses, genetic influences, and dietary/lifestyle changes. Consequently, INR values are out of the target range approximately half of the time in real-life studies compared to clinical trial setting. Current anticoagulation therapies are less likely to be cost-effective in routine clinical practice and need improvement. The aim of this review is to discuss the pharmacoeconomic consequences of this management strategy by analysing the optimal treatment option within specific age and risk groups, confirming current guidelines for a health economic perspective and considering the economic impact on health care policy. METHODS: An electronic search of the Medline/PubMed database from 1966 to 2005 was performed to identify articles dealing with all pharmacoeconomic aspects of stroke prevention in atrial fibrillation. The following search terms were used: 'atrial fibrillation', 'stroke', 'cost', 'warfarin'. RESULTS: Treatment with warfarin is cost-effective (versus aspirin or no therapy) in patients with AF at moderate-to-high risk of stroke. The cost-effectiveness of anticoagulation therapy is driven by the achieved risk reduction rather than the potential benefits estimated from clinical trials. Failure to maintain optimal anticoagulation places patients at risk of complications, the management of which is a significant cost driver. CONCLUSION: Improvement could be achieved by optimising physicians and patient's knowledge driven through prevention campaigns by health care policy.     

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.     

Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation

BackgroundNon-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved.AimsWe sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF).MethodsWe recruited hospitalised patients (2013–2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA₂DS₂-VASc and SAMe-TT₂R₂ scores with poor adherence.ResultsAmong 396 patients (median age 75.0 years, interquartile range [IQR] 70–80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12–33]; median ARMS score 17 [IQR 17–19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA₂DS₂-VASc and SAMe-TT₂R₂ scores were not associated with poor adherence.ConclusionsAdherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.

KEY MESSAGES

• Adherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.
• Independent patient-related factors rather than composite scores were associated with poor adherence.
• The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.

     

Is it safe to stop oral anticoagulation after catheter ablation for atrial fibrillation?

Introduction: Atrial fibrillation is the most common arrhythmia worldwide. Its increasing prevalence has made the use of oral anticoagulants for stroke prevention routine; however, their use after the blanking period of catheter ablation remains uncertain.

Areas covered: This review outlines the pros and cons of stopping oral anticoagulation after catheter ablation. Major databases such as Pubmed or Embase were used. The most relevant articles published were used along with major recommendations of society guidelines. Authors will also discuss different proposed mechanisms of atrial fibrillation and more importantly future directions in this topic.

Expert commentary: The use of oral anticoagulants after catheter ablation for atrial fibrillation is debatable; however, based on current guidelines, we support the use of oral anticoagulants after the blanking period of catheter ablation. Noteworthy is that although the risk of bleeding can be fatal in some cases, it does not outweigh the risk of a disabling stroke.     

高危老年非瓣膜性心房颤动患者抗凝治疗调查

目的 调查高危老年非瓣膜性心房颤动(NVAF)患者的抗凝治疗情况.方法 回顾性调查2008年1月至2010年1月住院治疗且CHADS2评分2分以上的198例NVAF患者,分析华法林的使用率和效果、未使用华法林原因,并探讨相应的对策.结果 (1)按指南须口服华法林者中,华法林实际应用仅51例(25.8%).服用阿司匹林107例,未抗栓40例.与无抗栓组、阿司匹林组对比,华法林组缺血性脑卒中发生率明显减少(P<0.05);与无抗栓组对比,阿司匹林组缺血性脑卒中发生率也减少(P<0.05).各组间出血、全因死亡情况均无统计学差异.(2)高龄、并存疾病多、用药复杂、肝肾功能障碍、认识不足及过分担心出血并发症是未使用华法林的主要原因.结论 目前必须加强高危老年NVAF患者长期抗凝治疗的管理.     

Stroke prevention in atrial fibrillation: current anticoagulation management and future directions

Atrial fibrillation (AF) is an important cause of stroke, and stroke risk stratification is critical to the management of patients with AF. Anticoagulation with warfarin is the current standard of care for stroke prevention in these patients, despite the need for close monitoring. Aspirin alone is not as effective. Warfarin is recommended for patients with AF and valvular disease or with AF and one or more stroke risk factors. Other novel anticoagulants and antiplatelet combinations are under investigation. Curative procedures for AF are possible, but their long-term safety and effect on stroke risk are unknown.     

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.