Pharmacological and Non-pharmacological Treatments for Stroke Prevention in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is associated with significant risk of stroke and other thromboembolic events, which can be effectively prevented using oral anticoagulation (OAC) with either vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, or edoxaban. Until recently, VKAs were the only available means for OAC treatment. NOACs had similar efficacy and were safer than or as safe as warfarin with respect to reduced rates of hemorrhagic stroke or other intracranial bleeding in the respective pivotal randomized clinical trials (RCTs) of stroke prevention in non-valvular AF patients. Increasing “real-world” evidence on NOACs broadly confirms the results of the RCTs. However, individual patient characteristics including renal function, age, or prior bleeding should be taken into account when choosing the OAC with best risk–benefit profile. In patients ineligible for OACs, surgical or interventional stroke prevention strategies should be considered. In patients undergoing cardiac surgery for other reasons, the left atrial appendage excision, ligation, or amputation may be the best option. Importantly, residual stumps or insufficient ligation may result in even higher stroke risk than without intervention. Percutaneous left atrial appendage occlusion, although requiring minimally invasive access, failed to demonstrate reduced ischemic stroke events compared to warfarin. In this review article, we summarize current treatment options and discuss the strengths and major limitations of the therapies for stroke risk reduction in patients with AF.     

Balancing bleeding and thrombotic risk with new oral anticoagulants in patients with atrial fibrillation

Atrial fibrillation (AF) markedly increases the risk of stroke. Warfarin is highly effective for the prevention of stroke in such patients, but it is difficult to use and causes bleeding. Three new oral anticoagulants have been approved for stroke prevention in AF patients, and are at least as effective as warfarin with better bleeding profiles. These new agents have changed and simplified our approach to stroke prevention, as the threshold for initiation of oral anticoagulation is lower. All patients with AF should be risk assessed using the CHA₂DS₂-VASc score, and all patients with a score of 1 or above (except women with female sex as their only risk factor on the CHA₂DS₂-VASc score) should be considered for oral anticoagulation with one of the new agents. Formal bleeding risk assessment is essential, and can be done by using the well-validated HAS-BLED score.     

Approach to the new oral anticoagulants in family practice: Part 1: comparing the options

Objective

To compare key features of the new oral anticoagulants (NOACs)—dabigatran, rivaroxaban, and apixaban—and to address questions that arise when comparing the NOACs.

Sources of information

PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE).

Main message

All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction).

Conclusion

The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common “what if” questions that arise in the long-term clinical follow-up and management of patients receiving NOACs.     

心房颤动抗凝治疗进展

心房颤动是临床上最常见的心律失常,增加卒中风险。华法林抗凝效果虽已受到广泛的肯定,但同时存在出血风险、治疗窗狭窄、需要长期监测国际标准化比率以调整药量等缺点。新型口服抗凝药的应用如达比加群、利伐沙班、阿哌沙班可有效预防卒中及血栓栓塞。经皮左心耳封堵术亦可成为预防心房颤动血栓事件的有效替代治疗方式。     

Novel Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: Focus on Apixaban

Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality, with a similar reduction in the rate of ischemic stroke and better tolerability. When compared with aspirin in the AVERROES trial, apixaban was associated with more effective reduction of stroke, a similar risk of major bleeding, and better tolerability. In this review article, the authors summarize the current knowledge on novel oral anticoagulants and discuss the clinical aspects of their use for stroke prevention in AF, with particular emphasis on apixaban.     

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.     

Atrial fibrillation and stroke prevention: brief observations on the last decade

Atrial fibrillation (AF) results in a substantial risk of mortality and morbidity from stroke and thromboembolism, and thus, a cornerstone of AF management requires appropriate and effective stroke prevention, which is oral anticoagulation. In the last decade, substantial changes in the landscape of stroke prevention in AF are evident. New knowledge has led to improved treatment options and guidelines have evolved. For example, stroke and bleeding risk assessment has now focused on use of the validated CHA₂DS₂-VASc and HAS-BLED scores, respectively to make clinical decisions. An important clinical practice shift is the initial identification of ‘low-risk’ patients, that is, CHA₂DS₂-VASc score = 0 (male) or 1 (females), who do not need any antithrombotic therapy. Subsequent to this step OAC can be offered to patients with ≥1 stroke risk factors. More recently, the SAMe-TT₂R₂ score has been proposed to aid decision-making, by using simple clinical variables by identifying those AF patients likely to do well on warfarin (SAMe-TT₂R₂ score 0-1) or those more likely to have poor anticoagulation control (SAMe-TT₂R₂ score >2), where a non-vitamin K antagonist oral anticoagulant may be a better option.     

心房颤动导管消融围术期不间断新型口服抗凝剂和不间断华法林抗凝导致心脏压塞风险的荟萃分析

目的 综合评估心房颤动(房颤)导管消融围术期不间断新型口服抗凝剂(novel oral anticoagulants, NOACs)和华法林抗凝导致心脏压塞的风险。方法 检索PubMed、EMBase和Cochrane Library数据库,获取从应用NOACs至2022年2月发表的房颤导管消融围术期NOACs不间断抗凝治疗和华法林不间断抗凝治疗导致心脏压塞的研究。并使用Cochrane偏倚风险评估工具和MINORS(methodological index for nonrandomized studies)进行文献质量评价,Review manager 5.3软件对所收集的数据进行统计学分析。结果 共纳入13项研究,7 701例房颤消融患者。此荟萃分析显示：房颤导管消融围术期不间断NOACs和华法林抗凝导致心脏压塞的风险差异无统计学意义(RR=0.79,95%CI:0.49～1.30,P=0.36)。亚组分析显示：房颤导管消融围术期NOACs和华法林不间断抗凝导致心脏压塞需要开胸手术干预或输血治疗的风险差异无统计学意义(RR=0.94,95%CI:0.48～1.86,P>0....     

Decision-Making in Clinical Practice: Oral Anticoagulant Therapy in Patients with Non-valvular Atrial Fibrillation and a Single Additional Stroke Risk Factor

Approximately 1 in 3–4 patients presenting with an ischemic stroke will also have atrial fibrillation (AF), and AF-related strokes can be effectively prevented using oral anticoagulant therapy (OAC), either with well-controlled vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs). In addition, OAC use (both VKAs and NOACs) is associated with a 26% reduction in all-cause mortality (VKAs) or an additional 10% mortality reduction with NOACs relative to VKAs. The decision to use OAC in individual AF patient is based on the estimated balance of the benefit from ischemic stroke reduction against the risk of major OAC-related bleeding [essentially intracranial hemorrhage (ICH)]. Better appreciation of the importance of VKAs’ anticoagulation quality [a target time in therapeutic range (TTR) of ≥70%] and the availability of NOACs (which offer better safety compared to VKAs) have decreased the estimated threshold for OAC treatment in AF patients towards lower stroke risk levels. Still, contemporary registry-based data show that OAC is often underused in AF patients at increased risk of stroke. The uncertainty whether to use OAC may be particularly pronounced in AF patients with a single additional stroke risk factor, who are often (mis)perceived as having a “borderline” or insufficient stroke risk to trigger the use of OAC. However, observational data from real-world AF cohorts show that the annual stroke rates in such patients are higher than in patients with no additional stroke risk factors, and OAC use has been associated with reduction in stroke, systemic embolism, or death in comparison to no therapy or aspirin, with no increase in the risk of bleeding relative to aspirin. In this review article, we summarize the basic principles of stroke risk stratification in AF patients and discuss contemporary real-world evidence on OAC use and outcomes of OAC treatment in AF patients with a single additional stroke risk factor in various real-world AF cohorts.     

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.     

Fitting the right non-vitamin K antagonist oral anticoagulant to the right patient with non-valvular atrial fibrillation: an evidence-based choice

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomized trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients. The randomized trials are supplemented by effectiveness and safety data from real-world observational cohorts following the availability of these drugs for use in everyday clinical practice. Given the clinical heterogeneity of AF patients, the available data from trials and real-world studies allow us to fit the right NOAC to the particular patient’s characteristics, with the aim of optimizing outcomes for the individual patient. This review article aims to provide a summary of the evidence on the performance of NOACs in AF patients with specific clinical characteristics. Evidence-based suggestions are presented to provide a simple and viable strategy for clinicians for the choice of a particular NOAC.

• KEY MESSAGE

• Given the different performance of the new-oral anticoagulants in patients with the different clinical situation, evidence-based choice of fitting the right new-oral anticoagulants to the patients is provided in this review article.

     

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.     

Dabigatran: an oral direct thrombin inhibitor for use in atrial fibrillation

Atrial fibrillation (AF) is well known as one of the leading causes of stroke and systemic embolism. Anticoagulation therapy is recommended in all patients at moderate-to-high risk of stroke. The vitamin K antagonist warfarin has traditionally been used in these patients but presents challenges in dosing and monitoring in these patients. The oral direct thrombin inhibitor dabigatran etexilate (Pradaxa®; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA) was recently approved for use in the US for preventing stroke and systemic embolism in patients with nonvalvular AF. Clinical trials have shown it to reduce the risk of stroke and systemic embolism when compared with warfarin (goal international normalized ratio [INR] 2–3) with a similar risk for severe bleeding. It can be given twice daily, with the dose adjusted for renal function. It does not have any dietary restrictions, has few drug interactions (except involving permeability [P]-glycoprotein [P-gp] agents), and does not require routine laboratory monitoring. Patients may experience significant dyspepsia with its use. Compared with warfarin there is increased risk for gastrointestinal bleeding and perhaps myocardial infarction. Currently, no reversal agent exists for use in situations of overdose or severe bleeding although some strategies have been suggested. Despite its high acquisition cost compared with warfarin, analysis using theoretical models has shown it to be cost-effective. Dabigatran offers a unique alternative to warfarin in patients with nonvalvular AF and can be beneficial in patients requiring anticoagulation therapy.     

New oral anticoagulants: An emergency department overview

As of September 2013, three new oral anticoagulants (NOACs) are now available for clinical use on the Pharmaceutical Benefits Scheme in Australia. All three are for stroke prevention in atrial fibrillation, and one will also be available for the treatment of deep venous thrombosis and pulmonary embolism. All have been evaluated in large, multicentre randomised clinical trials. These drugs show at least equivalent efficacy to the current standard of care, the vitamin K antagonist warfarin. Major bleeding rates are overall comparable with warfarin, but there is an important reduction in intracranial bleeding of approximately 50% with all NOAC agents. The NOACs are administered in a simple, fixed dose regimen. There are a few clinically important interactions with other medications or diet. Concerns exist about the potential for irreversible bleeding in the small number of patients in which that occurs. This short report will discuss the pharmacology of these agents, the indications for use, aspects of laboratory monitoring and the management of bleeding with these agents.     

Managing Antithrombotic Therapy in Patients With Both Atrial Fibrillation and Coronary Heart Disease

Purpose

Atrial fibrillation (AF) and coronary heart disease (CHD) commonly occur together. Previous consensus guidelines were published before the wide availability of novel oral anticoagulants (NOACs) and newer P2Y₁₂ antiplatelet agents. We examine recent evidence to guide management in 3 categories of patients with AF and CHD: patients with stable CHD, nonstented patients with recent acute coronary syndrome, and patients with a coronary stent requiring dual-antiplatelet therapy.

Methods

We conducted a literature search by evaluation of PubMed and other data sources including international meeting reports. We critically reviewed recent clinical trial and relevant registry evidence to update European and US consensus documents.

Findings

Oral anticoagulation with warfarin or NOACs is required to prevent embolic stroke in AF, and antiplatelet therapy is insufficient for this purpose. Antiplatelet therapy using monotherapy with aspirin is the standard of care in stable CHD. Dual-antiplatelet therapy with aspirin and clopidogrel or a new P2Y₁₂ inhibitor (dual-antiplatelet therapy) is needed to reduce coronary events after an acute coronary syndrome or after percutaneous coronary intervention. Combinations of these agents increase the risk of bleeding, and limited clinical trial evidence suggests that withdrawal of aspirin may reduce bleeding without increasing coronary events.

Implications

Available clinical trials and registries provide remarkably little evidence to guide difficult clinical decision making in patients with combined AF and CHD. In patients on triple antithrombotic therapy with vitamin K antagonists, aspirin, and clopidogrel, a single clinical trial indicates that withdrawal of aspirin may reduce bleeding risk without increasing the risk of coronary thrombosis. It is unclear whether this evidence applies to combinations of NOACs and newer P2Y₁₂ inhibitors. Clinical trials of combinations of the newer antithrombotic agents are urgently needed to guide clinical care.     

Recommendations for thromboprophylaxis in the 2012 focused update of the ESC guidelines on atrial fibrillation: a commentary

The objective of this article is to provide a commentary on the recommendations for stroke prevention from the 2012 focused update of the European Society of Cardiology guidelines on the management of atrial fibrillation and the evidence (or lack of it) supporting these recommendations. These guidelines strongly advocate a major clinical practice shift towards initially focusing on the identification of ‘truly low risk’ patients who do not need any antithrombotic therapy. After this initial decision‐making step, effective stroke prevention – that is, oral anticoagulation therapy (whether as well‐controlled adjusted dose warfarin or with one of the novel oral anticoagulants) – could be offered to patients with atrial fibrillation with ≥ 1 stroke risk factors. The 2012 focused update guideline also provides additional guidance on advances in stroke and bleeding risk assessment that are evident since publication of the 2010 guideline, as well as recommendations on the use of the novel oral anticoagulants and the left atrial appendage occlusion devices that have been increasingly used in European clinical practice over the last 2 years.     

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.     

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.     

Novel anticoagulants for stroke prevention in atrial fibrillation and chronic kidney disease

Atrial fibrillation (AF) is about three-times more prevalent in patients with chronic kidney disease and the prevalence of AF increases with the degree of renal impairment. Clinical studies have shown increased risk of stroke, bleeding and death in patients with chronic kidney disease and AF. Despite, this increased risk, anticoagulation is underutilized due to increased bleeding risk in this population. Recently direct thrombin inhibitors and factor Xa inhibitors have been shown to be more efficacious in stroke prevention with reduced bleeding than warfarin. As the usage of these novel anticoagulants increases it is important to understand the data available in regard to these high risk patients.     

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.