Acute anticoagulation adjustment in patients with atrial fibrillation at risk for stroke: approaches, strategies, risks and benefits

The acute management of anticoagulation in patients with atrial fibrillation to prevent stroke and other thromboembolic complications includes the use of individualized strategies tailored to the patient and based on the situation (cardioversion, surgeries, dental procedures, cardiac interventions, other invasive procedures and initiation of, or adjustment to, warfarin dosing). The vast range of choices can cause confusion and few randomized controlled clinical trials in this area provide adequate guidance. Chronic anticoagulation management is more straightforward since clinical evidence is ample, randomized clinical trial data provides cogent informaiton and guidelines have been established. Acute management of anticoagulation in patients with atrial fibrillation to prevent thromboembolic complications is often unrecognized but is emerging as a crucial, but challenging, and increasingly complex aspect of the care of patients with atrial fibrillation. This review addresses issues regarding such patients who may be at risk for stroke and require acute adjustments of anticoagulation (in light of, or in lieu of, chronic anticoagulation). Several promising new strategies are considered in light of established medical care. This analysis provides practical recommendations based on available data and presents results from recent investigations that may provide insight into future strategies.     

Ximelagatran: a new antithrombotic option in atrial fibrillation

Treatment strategies in patients with atrial fibrillation typically involve pharmacologic or interventional invasive therapies to suppress the rhythm, control ventricular contraction rates, or prevent thromboembolic complications. Current therapies used for rhythm conversion in atrial fibrillation may have undesirable risks or side effects that limit this approach. Lifelong anticoagulation may be necessary to prevent the formation of thrombus in the left atrial chamber that can travel into the cerebral circulation to cause a stroke. Currently, warfarin is the most commonly prescribed anticoagulant for this purpose. Unfortunately, many patients with atrial fibrillation may not receive warfarin because of the difficulties in dosing and maintaining desirable target goals. The oral direct thrombin inhibitor ximelagatran has several pharmacologic properties that provide a unique and potentially desirable treatment option. Clinical studies have demonstrated that ximelagatran, administered in twice-daily doses of 36 mg, is non-inferior to warfarin for thromboprophylaxis against stroke or systemic embolism in atrial fibrillation. The pharmacology of ximelagatran and clinical trials with its use in atrial fibrillation is reviewed.     

Management of Recent-onset Sustained Atrial Fibrillation: Pharmacologic and Nonpharmacologic Strategies

Purpose

Recent studies have highlighted significant variations in the management of recent-onset sustained atrial fibrillation (AF). We aim to provide a succinct and clear management algorithm for physicians treating patients with recent-onset sustained AF.

Methods

We performed a comprehensive search of the literature on the management of recent-onset sustained AF with focus on studies reporting cardioversion of AF, antiarrhythmic agents, and anticoagulation. We also reviewed recent practice guidelines on AF management.

Findings

This review provides a guide on a tailored management approach of patients with recent-onset sustained AF. After initial detailed clinical assessment, optimal rate and rhythm control options can be provided, depending on hemodynamic stability, duration of AF episode, and AF stroke risk. Issues surrounding electrical and pharmacologic cardioversion are discussed in detail. We emphasize the importance of thromboembolic risk assessment and appropriate anticoagulation surrounding the point of cardioversion. Last, we highlighted the need for appropriate specialized follow-up care after acute AF management.

Implications

Despite the highly heterogeneous clinical presentations, management of recent-onset sustained AF must include stroke risk assessment, appropriate anticoagulation, and follow-up care in all patients beyond optimum rate and rhythm control strategies.     

Acute management of atrial fibrillation: Part II. Prevention of thromboembolic complications

Family physicians should be familiar with the acute management of atrial fibrillation and the initiation of chronic therapy for this common arrhythmia. Initial management should include hemodynamic stabilization, rate control, restoration of sinus rhythm, and initiation of antithrombotic therapy. Part II of this two-part article focuses on the prevention of thromboembolic complications using anticoagulation. Heparin is routinely administered before medical or electrical cardioversion. Warfarin is used in patients with persistent atrial fibrillation who are at higher risk for thromboembolic complications because of advanced age, history of coronary artery disease or stroke, or presence of left-sided heart failure. Aspirin is preferred in patients at low risk for thromboembolic complications and patients with a high risk for falls, a history of noncompliance, active bleeding, or poorly controlled hypertension. The recommendations provided in this article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality.     

ATRIAL FIBRILLATION,THROMBOEMBOLISM AND ANTITHROMBOTIC THERAPY

Atrial fibrillation is the commonest sustained disorder of cardiac rhythm and is associated with increased risk of stroke and thromboembolic events. Warfarin (dose-adjusted to a target INR of 2.0-3.0) has been well established to reduce this risk of stroke by 68% (95% CI 50-79%), while aspirin provides a risk reduction of 21% (95% CI 0-38%). Nevertheless, warfarin confers a risk of bleeding and the inconvenience of regular monitoring checks, while aspirin seems effective only for certain low-risk subgroups. Thus there have been strenuous efforts to improve thromboprophylaxis in atrial fibrillation, by using low-intensity anticoagulation regimens, combination antiplatelet therapy and refinement of risk stratification strategies. Attempts at using a low-intensity, fixed-dose warfarin regimen have, however, been disappointing. For now, a strategy of risk stratification should be adopted to identify highest risk patients with atrial fibrillation who would benefit from anticoagulation.     

Antithrombotic medication for stroke prevention

This article provides the reader with an overview and an update on antithrombotic stroke-prevention strategies. Relevant journals were hand-searched by the authors to compile a broad, but not comprehensive, summary of innovative and clinically relevant studies. These findings were then summarized to provide an expert opinion on selected fields of medical stroke prevention. We conclude that aspirin, clopidogrel or dipyridamol–aspirin are the cornerstone therapies in patients with noncardioembolic stroke. More potent antiplatelet drugs or the combination of aspirin and clopidogrel prevent more ischemic events but also lead to more bleeding complications. For secondary stroke prevention in patients with atrial fibrillation, oral anticoagulation is more effective than aspirin or the combination of aspirin and clopidogrel.     

Safety of electrical cardioversion in patients with previous embolic events

OBJECTIVE: To assess thromboembolic complications in cardioversions in patients with atrial fibrillation or flutter and a previous embolic event. PATIENTS AND METHODS: The study population consisted of 104 patients with previous embolic events who underwent 128 electrical cardioversions for termination of atrial fibrillation or flutter. The primary outcome measure was successful cardioversion. RESULTS: Anticoagulants were administered in 118 procedures (92%). Cardioversion was successful in 108 (84%) of the 128 procedures. Only 1 embolic event occurred within 30 days after cardioversion (incidence, 0.9% of successful procedures; 95 % confidence interval, 0.02%-5.3%). The single embolic event was a transient neurologic deficit occurring 22 days after cardioversion in a patient with previous atrial fibrillation. This patient had a sub-therapeutic level of anticoagulation. Transesophageal echocardiography revealed no spontaneous echo contrast or thrombi before the procedure. No thromboembolism was noted in patients who had therapeutic anticoagulation or in those with failed cardioversion. CONCLUSION: Patients with previous embolism are not at additional risk of thromboembolic complications after cardioversion if anticoagulation is adequate.     

The Importance of Atrial Fibrillation Burden and the Origin of Device‐Tailored Anticoagulation

The current paradigm for anticoagulation in patients with atrial fibrillation is based upon clinical risk factors for stroke without reference to the frequency or duration (i.e., burden) of atrial fibrillation episodes. In the last decade, increasing evidence derived from device‐based surveillance of atrial fibrillation has suggested that in some patients the burden of atrial fibrillation may be associated with thromboembolic risk. The development of rapidly acting oral anticoagulants and devices with remote monitoring capability has allowed the testing of a strategy of tailored or “pill‐in‐the‐pocket” anticoagulation based upon atrial fibrillation burden.     

缺血性卒中的抗凝治疗

几个大规模、多中心、随机试验发现,天然肝素(UFH)或低分子肝素(LMWH)并不能改善急性缺血性卒中患者的总体预后。紧急抗凝可预防长期卧床急性缺血性卒中患者深静脉血栓的形成。伴房颤及附加危险因素,如附壁血栓和(或)新发心肌梗死的心源性栓塞性卒中患者具有较高复发性卒中危险,若无显著出血可紧急抗凝。华法令抗凝可作为伴心房纤颤卒中患者的初级和二级预防。颅内静脉窦栓塞形成、颈动脉夹层和抗磷脂抗体综合征患者可常规抗凝,而非心源性栓塞性卒中或症状性颅内动脉狭窄综合征患者长期抗凝治疗证据不足。     

Ximelagatran for stroke prevention in atrial fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia and the most frequently encountered cause of embolic stroke. Vitamin K antagonists (such as warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with atrial fibrillation, warfarin therapy is limited by a multitude of potential problems. Hence, warfarin is significantly underused in clinical practice, with only half of warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral anticoagulant for patients with atrial fibrillation that is safer, more practical and effective. Ximelagatran (Exanta®, AstraZeneca) is a novel oral direct thrombin inhibitor that is rapidly converted to the active compound melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The Stroke Prevention using the ORal Thrombin Inhibitor in patients with nonvalvular atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of ximelagatran relative to warfarin for the prevention of stroke and embolic events in atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver enzymes.     

Atrial Fibrillation: Maintaining Stability of Sinus Rbythm or Ventricular Rate Control? The Need for Prospective Data: The PIAF Trial

Atrial fibrillation is one of the most commonly encountered clinical arrhythmias. Different treatment options for this rhythm disorder exist with the electrical and/or pharmacological cardioversion to sinus rhythm with subsequent antiarrhythmic drug therapy to prevent recurrences being one of the primary therapeutic goals. Another alternative, however, is represented by the control of the ventricular rate in patients with persistent atrial fibrillation. The question of which of these two strategies should be preferred in the majority of patients with atrial fibrillation has not been studied in a prospective way. Given the background of conflicting data with respect to the prognostic impact of atrial fibrillation and of the increasing evidence concerning the risks of antiarrhythmic drug treatment in atrial fibrillation, a prospective multicenter trial has been initiated to compare these two therapeutic alternatives prospectively. Patients will be randomly assigned to cardioversion with subsequent antiarrhythmic drug therapy to prevent recurrent atrial fibrillation or to a therapy aiming exclusively at control of the ventricular rate during persistent atrial fibrillation. All patients will receive anticoagulation by means of warfarin (target INR 2.5-3.5) to prevent thromboembolic complications. The rationale and the design of the PIAF trial (Pharmacological Intervention in Atrial Fibrillation) are discussed below. The pilot phase of this study has begun patient enrollment in the spring of 1995.     

Anticoagulant therapy for atrial fibrillation. Recommendations from major studies.

The role of antithrombotic therapy in reducing thromboembolic complications in patients with chronic atrial fibrillation has been clarified by the results of four major randomized and placebo-controlled trials. Patients with rheumatic heart disease complicated by atrial fibrillation should receive long-term warfarin therapy to reduce the risk of stroke unless an absolute contraindication exists. Patients with nonrheumatic atrial fibrillation should also be treated with low-dose warfarin therapy, especially if high-risk features for thromboembolism exist. In patients who have contraindications to warfarin therapy and in young patients with lone atrial fibrillation or paroxysmal atrial fibrillation, therapy with 325 mg of aspirin a day is preferred. Ongoing trials directly comparing aspirin and warfarin will provide additional insight into the optimal role of these antithrombotic agents in patients with atrial fibrillation.     

Atrial High Rate Episodes in Patients with Dual‐Chamber Cardiac Implantable Electronic Devices: Unmasking Silent Atrial Fibrillation

Assessment of the prevalence of silent paroxysmal atrial fibrillation (AF) represents a challenge, since the arrhythmia may be brief, completely asymptomatic, and difficult to detect. Lack of symptoms from AF should not be equated to lack of risk of thromboembolic complications. Today's cardiac implantable electronic devices (CIED) diagnostics include system diagnostics accurately revealing asymptomatic cardiac arrhythmias as atrial high rate episodes (AHRE). The presence of AHRE has been related to increased risk of stroke and systemic embolism. The application of anticoagulation therapy in patients with device‐detected AHRE is yet unclear and challenging in the absence of randomized studies. Until further studies are available, anticoagulation therapy should be individualized and promoted attending to the CHADS₂ score. Future guidelines should deal with this peculiar AF scenario to make professionals who routinely perform CIED follow‐ups aware of these relevant episodes and their clinical implications.     

A review of the literature on atrial fibrillation: rate reversion or control?

Aims. The aim of this paper is to review the current literature describing the aetiology of atrial fibrillation and to examine the evidence for rate reversion and rate control. Background. Atrial fibrillation is the most commonly seen arrhythmia within the clinical setting. Treatment depends on severity of symptoms, which are predominantly palpitations and shortness of breath. The primary complications from atrial fibrillation are thrombo‐embolic events (such as a pulmonary embolus or stroke). Objectives and methods. A comprehensive literature review on atrial fibrillation, rate reversion and rate control was undertaken to examine the incidence of atrial fibrillation, to review research on management of atrial fibrillation and to determine if rate reversion was superior to rate control in the treatment of atrial fibrillation. Results. Many studies have been carried out to determine the best treatment for this condition. The choices are currently pharmacological and electrical cardioversion in conjunction with anticoagulant therapy. Drug therapies are not without their problems, especially toxicity and the need for close clinical monitoring. Transaesophageal echocardiography has been used to establish the presence of left atrial thrombi and aims to reduce the anticoagulation time and reduce the risk of thrombo‐embolic events. A randomized comparative study of transaesophageal echocardiography and conventional anticoagulation therapy prior to cardioversion demonstrated statistically significant reduction in haemorrhagic events and a shorter time to cardioversion in those in the transaesophageal echocardiography group compared with the conventional group. For those with persistent atrial fibrillation, surgery is an option with valve repair or replacement carried out in conjunction with a bi‐atrial surgical ablation. Conclusions. The management of atrial fibrillation is dependent on many factors and to date there are no proven clinical rationale for rate control or reversion. Relevance to clinical practice. Atrial fibrillation requires immediate attention in order to avoid thrombo‐embolic complications and the use of transaesophageal echocardiography and conventional anticoagulation therapy can significantly reduce these complications.     

Cardioversion for atrial fibrillation – how to prevent thromboembolic complications?

Abstract

Cardioversion is an essential component of rhythm control strategy for atrial fibrillation. The thromboembolic risk of cardioversion is well established and the mechanisms behind the phenomenon have been comprehensively described. There are several clinical aspects that are important to take into consideration when assessing the safety of cardioversion. Before proceeding to cardioversion, the probability of early treatment failure and antiarrhythmic treatment options to prevent recurrences should be carefully evaluated to avoid the risks of repeated futile cardioversions. Effective periprocedural anticoagulation is the mainstay in thromboembolic complication prevention and the first week after rhythm conversion is the most vulnerable period in this respect. Early timing of cardioversion appears to be another important measure to decrease the risk of thromboembolic complications. Transoesophageal echocardiography is useful in clinical scenarios where early cardioversion is desirable due to debilitating clinical symptoms and a short duration of arrhythmia or the adequacy of preceding anticoagulation is uncertain. However, it does not lessen the need for effective anticoagulation after cardioversion. This review summarizes the recent scientific discoveries to improve the safety of cardioversion for atrial fibrillation.

• Key messages

• Cardioversion for atrial fibrillation entails a significant risk of thromboembolic complications, especially during the first week after the procedure.

• The intensity of periprocedural anticoagulation and the timing of cardioversion appear to be significant determinants of the risk of thromboembolism.

• Awareness of the clinical aspects influencing cardioversion safety should be raised.

     

Atrial fibrillation among older adults: pathophysiology, symptoms, and treatment

Atrial fibrillation is the most common arrhythmia among older adults. Valvular heart disease, dilated cardiomyopathy, aortic stenosis, hypertension, coronary artery disease, pericarditis, thyrotoxicosis, pulmonary disease, cardiac surgery, alcohol excess, and alcohol withdrawal are associated with atrial fibrillation. Nurses caring for older adults need to understand the condition's pathophysiology, signs and symptoms, diagnostic data and treatment protocols, and adherence issues to prevent the formation of emboli in chronic atrial fibrillation and to understand treatment of this common arrhythmia. This article presents an individual example of an elderly man exhibiting a new onset of atrial fibrillation and the interventions required to manage the associated complications. Atrial fibrillation places patients at risk for stroke from a thromboembolism; thus, pharmacological and nonpharmocological care strategies for managing patients with atrial fibrillation are discussed.     

Novel drugs for oral anticoagulation pharmacotherapy

Long-term anticoagulation with warfarin is the mainstay of treatment in patients with diseases with high thromboembolic potential, such as atrial fibrillation. However, warfarin therapy carries a number of inherent limitations, including slow onset and offset of action, interindividual variability, food and drug interactions, lack of selectivity and a narrow therapeutic window. Recently developed oral anticoagulants that selectively block key factors in the coagulation cascade, with no need for monitoring or dose adjustment, have the potential to replace warfarin in clinical practice. The safety and efficacy of these agents in patients with atrial fibrillation, venous thromboembolisms and acute coronary syndromes have been the object of numerous recent large-scale clinical investigations. This article provides an overview of the evidence currently available on the use of novel, orally available, selective anticoagulants in patients at risk for thromboembolic events.     

Ximelagatran for stroke prevention in atrial fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia and the most frequently encountered cause of embolic stroke. Vitamin K antagonists (such as warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with atrial fibrillation, warfarin therapy is limited by a multitude of potential problems. Hence, warfarin is significantly underused in clinical practice, with only half of warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral anticoagulant for patients with atrial fibrillation that is safer, more practical and effective. Ximelagatran (Exanta, AstraZeneca) is a novel oral direct thrombin inhibitor that is rapidly converted to the active compound melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The Stroke Prevention using the ORal Thrombin Inhibitor in patients with nonvalvular atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of ximelagatran relative to warfarin for the prevention of stroke and embolic events in atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver enzymes.     

AUDITS: Mnemonical Approach for Atrial Fibrillation With Coronary Artery Disease

Managing anticoagulation therapy in patients with acute coronary syndrome and atrial fibrillation requires effective use of risk stratification scores to optimize treatment options while weighing the risk of stroke or systemic thromboembolism vs the risk of bleeding. A mnemonic-based clinical practice pathway is proposed to provide nurse practitioners with a structured approach to managing patients with atrial fibrillation in the context of an acute coronary syndrome. The AUDITS mnemonic represents a simplified treatment guide derived from current guidelines and aims to help nurse practitioners implement best practices to ensure patient safety.     

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.