Rate versus rhythm control in the management of patients with atrial fibrillation

The management of patients with atrial fibrillation involves three main areas: anticoagulation, rate control and rhythm control. Importantly, these are not mutually exclusive of each other. Anticoagulation is necessary for patients who are at a high risk of stroke; for example, those who are older than 75 years, or those who have hypertension, severe left ventricular dysfunction, previous cerebrovascular events, or diabetes. It is now clear that patients who are at a high risk of stroke require long-term anticoagulation with warfarin regardless of whether a rate-control or rhythm-control strategy is chosen. One possible exception might be patients who are apparently cured with catheter ablation. Several published trials comparing rate-control and rhythm-control strategies for the treatment of patients with atrial fibrillation have shown no difference in mortality between these approaches. The patients enrolled in these studies were typically over 65 years of age. Data comparing rate and rhythm strategies in patients who are younger than 60 years of age are limited. For more elderly patients, it seems reasonable to consider rate control as a primary treatment option and to reserve rhythm control for those who do not respond to rate control. For younger patients, we prefer to start with a rhythm-control approach and to reserve rate-control approaches for patients in whom antiarrhythmic drugs, ablation, or both, do not ameliorate the symptoms.     

Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study

PURPOSE: Randomized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation. However, these trials have reported too few strokes for powerful risk factor analysis. Observational studies may provide additional information. The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation, using case-control methodology. PATIENTS AND METHODS: We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke (n = 134), and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke (n = 131). RESULTS: Cases and controls were similar in terms of duration of atrial fibrillation; proportion with paroxysmal atrial fibrillation; percentage with a past medical history of angina, myocardial infarction, congestive heart failure, diabetes, or smoking; and mean left atrial size. In contrast, cases were significantly older than controls (78.5 versus 74.8 years, p = 0.002) and more likely to have a history of hypertension (55% versus 38%, p = 0.0093). The relative odds for stroke was 1.91 for patients with hypertension, 1.73 for patients older than 75 years, and 3.26 for patients with both factors. CONCLUSIONS: Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation.     

Risk of stroke in patients with atrial flutter

Using a Medicare-based retrospective cohort study, the stroke risk in patients with atrial flutter (RR = 1.41) was determined to be greater than that in a control group (RR = 1.00) but less than that in an atrial fibrillation group (RR = 1.64). Furthermore, patients with atrial flutter who subsequently had an episode of atrial fibrillation had a higher risk of stroke (RR = 1.56) than patients with atrial flutter who never had a subsequent episode of atrial fibrillation (RR = 1.11).     

Atrial fibrillation

The management of atrial fibrillation has evolved greatly in the past few years, and many areas have had substantial advances or developments. Recognition of the limitations of aspirin and the availability of new oral anticoagulant drugs that overcome the inherent drawbacks associated with warfarin will enable widespread application of effective thromboprophylaxis with oral anticoagulants. The emphasis on stroke risk stratification has shifted towards identification of so-called truly low-risk patients with atrial fibrillation who do not need antithrombotic therapy, whereas oral anticoagulation therapy should be considered in patients with one or more risk factors for stroke. New antiarrhythmic drugs, such as dronedarone and vernakalant, have provided some additional opportunities for rhythm control in atrial fibrillation. However, the management of the disorder is increasingly driven by symptoms. The availability of non-pharmacological approaches, such as ablation, has allowed additional options for the management of atrial fibrillation in patients who are unsuitable for or intolerant of drug approaches.     

Atrial fibrillation and coagulation: Who and when?

Atrial fibrillation is an independent risk factor for stroke and is also associated with increased mortality above the age of 65 in both males and females. Various factors increase the stroke risk, with the most widely used risk assessment tool being the CHADS2 score which incorporates, heart failure, hypertension, age, diabetes and hitroys of previous stroke or transient ischaemic attack. Despite good evidence for the effectiveness of warfarin in preventing stroke and reducing mortality in atrial fibrillation, there remain a large proportion of patients who do not receive appropriate treatment. All patients with atrial fibrillation should be considered for warfarin therapy aiming for an INR of 2.5. Whilst newer agents may replace warfarin in the future, the evidence for anti-platelet therapy is poor and aspirin should be reserved only for patients who have very low stroke risk or those patients who cannot tolerate warfarin therapy.     

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.     

Atrial fibrillation

The prevalence and incidence of atrial fibrillation increase with age. Atrial fibrillation is associated with a higher incidence of coronary events, stroke, and mortality than sinus rhythm. A fast ventricular rate associated with atrial fibrillation may cause tachycardia-related cardiomyopathy. Management of atrial fibrillation includes treatment of underlying causes and precipitating factors. Immediate direct-current cardioversion should be performed in persons with atrial fibrillation associated with acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta-blockers, verapamil, or diltiazem may be used to immediately slow a fast ventricular rate associated with atrial fibrillation. An oral beta-blocker, verapamil, or diltiazem should be given to persons with atrial fibrillation if a rapid ventricular rate occurs a rest or during exercise despite digoxin. Amiodarone may be used in selected persons with symptomatic life-threatening atrial fibrillation refractory to other drug therapy. Nondrug therapies should be performed in persons with symptomatic atrial fibrillation in whom a rapid ventricular rate cannot be slowed by drug therapy. Paroxysmal atrial fibrillation associated with the tachycardia-bradycardia syndrome should be managed with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in persons with atrial fibrillation in whom symptoms such as dizziness or syncope associated with non-drug-induced ventricular pauses longer than 3 seconds develop. Elective direct-current cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than medical cardioversion in converting atrial fibrillation to sinus rhythm. Unless transesophageal echocardiography shows no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective direct-current or drug cardioversion of atrial fibrillation and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer the treatment strategy of ventricular rate control plus warfarin rather than to maintain sinus rhythm with antiarrhythmic drugs, especially in older patients. Digoxin should not be used in persons with paroxysmal atrial fibrillation. Patients with chronic or paroxysmal atrial fibrillation who are at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio (INR) of 2.0 to 3.0. Persons with atrial fibrillation who are at low risk for stroke or who have contraindications to warfarin should receive 325 mg aspirin daily.     

Atrial fibrillation as a risk factor for stroke recurrence

BACKGROUND: Although atrial fibrillation is a well-known risk factor for ischemic stroke, the extent to which it increases the risk of stroke recurrence, particularly in elderly patients, is less certain. METHODS: We performed a retrospective cohort study of 915 patients aged 50 to 94 years who were admitted with an ischemic stroke. The rates of recurrent strokes and recurrent severe strokes were estimated with the Kaplan-Meier method. The effects of atrial fibrillation on stroke risk were analyzed with proportional hazards models. RESULTS: Of the 829 patients who survived the initial hospitalization, 163 (20%) had a stroke during follow-up. Of the 203 patients with atrial fibrillation during index hospitalization who were not anticoagulated, 54 (27%) had recurrent strokes, compared with 18% (19/103) among those with atrial fibrillation who were anticoagulated and 17% (90/523) among those without atrial fibrillation. The age-adjusted hazard ratio for recurrent stroke among those with atrial fibrillation who were not treated with anticoagulants was 2.1 (95% confidence interval [CI]: 1.4 to 2.9; P <0.001), whereas the hazard ratio for recurrent severe stroke was 2.4 (95% CI: 1.6 to 3.6; P <0.001). The increased risk was observed even in patients aged > or = 80 years and persisted during the follow-up for more than 5 years. CONCLUSION: Atrial fibrillation was an independent risk factor for stroke recurrence over a wide age range.     

Silent Atrial Fibrillation and Cryptogenic Strokes

A new suspected cause of cryptic strokes is “silent atrial fibrillation.” Pacemakers and other implanted devices allow continuous recording of cardiac rhythm for months or years. They have discovered that short periods of atrial fibrillation lasting minutes or hours are frequent and usually are asymptomatic. A meta-analysis of 50 studies involving more than 10,000 patients with a recent stroke found that 7.7% had new atrial fibrillation on their admitting electrocardiogram. In 3 weeks during and after hospitalization, another 16.9% were diagnosed. A total of 23.7% of these stroke patients had silent atrial fibrillation; that is, atrial fibrillation diagnosed after hospital admission. Silent atrial fibrillation is also frequent in patients with pacemakers who do not have a recent stroke. In a pooled analysis of 3 studies involving more than 10,000 patients monitored for 24 months, 43% had at least 1 day with atrial fibrillation lasting more than 5 minutes. Ten percent had atrial fibrillation lasting at least 12 hours. Despite the frequency of silent atrial fibrillation in these patients with multiple risk factors for stroke, the annual incidence of stroke was only 0.23%. When silent atrial fibrillation is detected in patients with recent cryptogenic stroke, anticoagulation is indicated. In patients without stroke, silent atrial fibrillation should lead to further monitoring for clinical atrial fibrillation rather than immediate anticoagulation, as some have advocated.     

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.     

Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation

Purpose: The risk of ischemic stroke varies widely among patients with nonvalvular atrial fibrillation, influencing the choice of prophylactic antithrombotic therapy. We assessed three schemes for stroke risk stratification in these patients who were treated with aspirin and who did not have prior cerebral ischemia.SUBJECTS AND METHODS: Criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low, ineffective doses of warfarin in a multicenter clinical trial. The ability of the schemes to identify patients at high (>/=6%), low (75 years old as high risk (observed stroke rate 4.2 per 100 person-years), while the remaining scheme classified one third of patients in this age group as low risk (observed stroke rate 0.6 per 100 person-years). CONCLUSIONS: When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin, available risk-stratification schemes successfully identified patients with low rates of ischemic stroke, but less consistently identified high-risk patients.     

Atrial fibrillation in the elderly

Atrial fibrillation is the most common arrhythmia in the United States, whose incidence is greatest in the elderly population. This rhythm disorder can be paroxysmal or chronic and is associated with a range of clinical conditions from palpitations and dyspnea to stroke and death. In the elderly the mainstay of treatment of atrial fibrillation should utilize drug therapy. The main goals of drug therapy should be effective rate control to avoid tachycardia-induced cardiomyopathy, anticoagulation to reduce the risk of stroke and thromboembolism, and maintenance of sinus rhythm to prevent adverse atrial remodeling. In those patients in whom effective rate control cannot be achieved, catheter ablation of the atrioventricular node and implantation of a permanent pacemaker should be considered. Catheter ablation of atrial fibrillation by targeting pulmonary venous foci or pulmonary venous isolation currently remains investigational and we advocate its use be limited to symptomatic patients who have failed traditional therapy.     

Antithrombotic therapy in atrial fibrillation

Warfarin is highly effective at reducing the risk of stroke in atrial fibrillation. The benefit of oral anticoagulant therapy strongly outweighs the risk in most patients with atrial fibrillation. More data are needed to define better the overall risk-to-benefit ratio for patients age 80 years and greater. Because a significant proportion of elderly individuals may not be optimal candidates for anticoagulant therapy, alternative stroke prevention strategies must continue to be evaluated while redoubling efforts to understand the mechanisms underlying atrial fibrillation and thrombogenesis.     

老年心房颤动患者的抗凝策略与抗凝强度评价

房颤是一个严重的临床问题,随着年龄增长,其发病率逐渐增高。房颤所导致的血栓栓塞并发症高,致死、致残率高,未经治疗的房颤患者脑卒中年发生率平均为5%。在临床工作中,年龄是房颤患者血栓栓塞危险分层及指导抗凝策略的重要因素,对75岁以上、肾功能异常、高血压未能良好控制者在抗凝治疗中应加强监测,可考虑适当降低抗凝强度,以防止出血并发症。     

Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians

The Joint Panel of the American Academy of Family Physicians and the American College of Physicians, in collaboration with the Johns Hopkins Evidence-based Practice Center, systematically reviewed the available evidence on the management of newly detected atrial fibrillation and developed recommendations for adult patients with first-detected atrial fibrillation. The recommendations do not apply to patients with postoperative or post-myocardial infarction atrial fibrillation, patients with class IV heart failure, patients already taking antiarrhythmic drugs, or patients with valvular disease. The target physician audience is internists and family physicians dedicated to primary care. The recommendations are as follows: RECOMMENDATION 1: Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation. Rhythm control has not been shown to be superior to rate control (with chronic anticoagulation) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control. Rhythm control is appropriate when based on other special considerations, such as patient symptoms, exercise tolerance, and patient preference. Grade: 2A. RECOMMENDATION 2: Patients with atrial fibrillation should receive chronic anticoagulation with adjusted-dose warfarin, unless they are at low risk of stroke or have a specific contraindication to the use of warfarin (thrombocytopenia, recent trauma or surgery, alcoholism). Grade: 1A. RECOMMENDATION 3: For patients with atrial fibrillation, the following drugs are recommended for their demonstrated efficacy in rate control during exercise and while at rest: atenolol, metoprolol, diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is only effective for rate control at rest and therefore should only be used as a second-line agent for rate control in atrial fibrillation. Grade: 1B. RECOMMENDATION 4: For those patients who elect to undergo acute cardioversion to achieve sinus rhythm in atrial fibrillation, both direct-current cardioversion (Grade: 1C+) and pharmacological conversion (Grade: 2A) are appropriate options. RECOMMENDATION 5: Both transesophageal echocardiography with short-term prior anticoagulation followed by early acute cardioversion (in the absence of intracardiac thrombus) with postcardioversion anticoagulation versus delayed cardioversion with pre- and postanticoagulation are appropriate management strategies for those patients who elect to undergo cardioversion. Grade: 2A. RECOMMENDATION 6: Most patients converted to sinus rhythm from atrial fibrillation should not be placed on rhythm maintenance therapy since the risks outweigh the benefits. In a selected group of patients whose quality of life is compromised by atrial fibrillation, the recommended pharmacologic agents for rhythm maintenance are amiodarone, disopyramide, propafenone, and sotalol (drugs listed in alphabetical order). The choice of agent predominantly depends on specific risk of side effects based on patient characteristics. Grade: 2A.     

Postprandial hyperglycemia is a possible contributor to paroxysmal atrial fibrillation: a case report

Atrial fibrillation, a major risk factor for stroke, is believed to occur first as paroxysmal episodes, gradually becoming more persistent, and finally progressing to chronic atrial fibrillation. Treatment of paroxysmal atrial fibrillation is an important target to prevent chronic atrial fibrillation. We describe a very unique case with postprandial hyperglycemia and obesity associated with drug-refractory paroxysmal atrial fibrillation. A 73-year-old Japanese woman with postprandial hyperglycemia suffered from drug-refractory paroxysmal atrial fibrillation. A 1600 kcal/day diet and walking three times/day for more than 30 min eliminated paroxysmal atrial fibrillation after 6 months. Diet and exercise should be considered as the initial therapy in patients with paroxysmal atrial fibrillation who also have postprandial hyperglycemia. This case suggests that postprandial hyperglycemia and insulin resistance might be one of the possible underlying mechanisms of paroxysmal atrial fibrillation.     

Lessons from the Stroke Prevention in Atrial Fibrillation trials

Atrial fibrillation predisposes to left atrial thrombus formation and carries a sixfold increased risk for stroke. Antithrombotic therapies are the mainstay for stroke prevention. The National Institute of Neurological Disorders and Stroke-sponsored Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and their combination for preventing stroke in six multicenter trials involving 3950 participants. This review presents the major results and implications, which offer unique perspectives on antithrombotic therapies for stroke prevention in atrial fibrillation. Warfarin and aspirin reduce stroke. Anticoagulation substantially benefits high-risk patients with atrial fibrillation, while many younger patients with atrial fibrillation have a low stroke rate when given aspirin. Pathogenetic and transesophageal echocardiographic correlations shed light on mechanisms by which antithrombotic agents prevent stroke. Warfarin inhibits formation of atrial appendage thrombi and markedly reduces cardioembolic strokes, while aspirin primarily prevents smaller, noncardioembolic strokes. The SPAF III stroke risk stratification scheme has been validated for identifying patients with high versus moderate versus low risk for stroke. Women with atrial fibrillation benefit from anticoagulation significantly more than men do. Many elderly patients with recurrent paroxysmal atrial fibrillation have high rates of stroke. Antithrombotic prophylaxis should be individualized on the basis of the estimated risk for stroke during aspirin therapy and the risk for bleeding during anticoagulation. Overall, nearly one third of patients with atrial fibrillation are low risk and should be treated with aspirin, and about one third are high risk and should receive warfarin if it can be given safely. For patients at moderate risk for stroke, patient preferences and access to reliable anticoagulation monitoring are particularly relevant.     

迷宫手术对心房纤颤患者中风的影响

目的探讨迷宫手术对心房纤颤患者中风的影响。方法自1994年10月至1999年3月,我们对53例内科治疗无效的房颤患者进行了迷宫术治疗,其中有8例术时正患有中风,6例有中风史,3例术前曾有短暂性脑缺血(TIA)。结果迷宫术后53例患者经6.5年的随访,仅有1例(1.7%)近期有不严重的中风。结论迷宫术能非常显著的减少房颤合并中风的危险性。     

非瓣膜病房颤缺血性脑卒中的预防

非瓣膜病房颤缺血性脑卒及体动脉栓塞的发病率很高,预防这一事件的发生现已成为国内外研究的热题。抗凝治疗无疑是卒中预防中重要环节之一,新型口服抗凝剂相较华法林可能对亚洲房颤人群血栓栓塞的预防效果更好,不良事件发生率更低,正在成为一种全新的选择。随着左心耳封堵技术日渐成熟,给不适合抗凝治疗的房颤患者带来了福音。许多大型临床研究显示射频消融不仅可以恢复窦律,还可以降低房颤负荷,减少血栓栓塞事件的发生,对于栓塞风险较高的病人来说,新型口服抗凝药联合射频消融对卒中预防效果可能会更好。肥胖、吸烟、嗜酒、高血压、糖尿病等危险因素在房颤病程进展中扮演了重要角色,包括房颤危险因素在内的综合管理对缺血性脑卒中的预防效果更佳。     

Schlaganfallprophylaxe bei Vorhofflimmern

Atrial fibrillation is the most common form of cardiac arrhythmia with an age-dependent increase in prevalence. It is common clinical practice to treat patients with atrial fibrillation and who have a high risk for thromboembolic stroke with vitamin K antagonists. However, due to the many problems with vitamin K antagonist therapy many high risk patients are either not treated at all or receive insufficient anticoagulation treatment. The new oral anticoagulants, e.g. dabigatran as a direct thrombin antagonist or rivaroxaban and apixaban as factor Xa antagonists were tested in large scale clinical trials with respect to the efficacy in stroke prevention in atrial fibrillation patients. The therapeutic superiority over warfarin could be impressively proven either with respect to the efficacy in stroke prevention and/or to the safety of therapy with a significant decrease in cerebral bleeding complications.