Copia de Atrial Fibrillation

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Overview of the evaluation and manag
Offic ial reprint from UpToDate www.uptodate.c om 2011 UpToDate
Overview of the evaluation and management of atrial fibrillation

Author Philip J Podrid, MD Section Editor Peter J Zimetbaum, MD Deputy Editor Gordon M Saperia, MD, FACC
Last literature review version 19.1: enero 2011 |
This topic last updated: enero 8, 2010
INTRODUCTION Atrial fibrillation (AF) is a relatively c ommon arrhythmia that is more prevalent in men and with increasing age (figure 1) [1]. AF can have adverse consequenc es related to a reduction in c ardiac output and to atrial and atrial appendage thrombus formation that c an lead to systemic embolization [2-5]. This topic review will foc us on the following areas: classific ation of AF; initial evaluation; general treatment issues; and mortality assoc iated with AF. The presentation and management of new onset AF is discussed separately. (See "Management of new onset atrial fibrillation".) CLASSIFICATION Atrial fibrillation occ urs in the normal heart and in the presenc e of organic heart disease of any cause. (See "Epidemiology of and risk factors for atrial fibrillation".) The following c lassification for AF when first detec ted has been proposed by the 2006 Americ an College of Cardiology/Americ an Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines on atrial fibrillation [6]. Paroxysmal (ie, self-terminating) AF is c lassified as paroxysmal if episodes terminate spontaneously in less than seven days, usually less than 24 hours. (See "Paroxysmal atrial fibrillation".) Persistent AF AF is classified as persistent if it fails to self-terminate within seven days. Episodes may eventually terminate spontaneously, or they c an be terminated by cardioversion. A patient who has had an episode of persistent AF can have later episodes of AF that c lassify as paroxysmal (ie, self-terminating in less than seven days). Permanent AF Permanent AF is c onsidered to be present if the arrhythmia lasts for more than one year and cardioversion either has not been attempted or has failed. Lone AF Lone AF describes paroxysmal, persistent, or permanent AF in individuals without structural heart disease. Lone AF has primarily been applied to patients 60 years of age but older patients also may be at low risk. This c lassification applies to episodes of AF that last more than 30 seconds and that are unrelated to a reversible cause. If the AF is sec ondary to c ardiac surgery, peric arditis, myoc ardial infarc tion (MI), hyperthyroidism, pulmonary embolism, pulmonary disease, or other reversible c auses, therapy is directed toward the underlying disease as well as the AF. (See "Epidemiology of and risk fac tors for atrial fibrillation".) EVALUATION The history, physic al examination, and specific laboratory and cardiologic testing are all part of the evaluation of the patient with AF. The minimum evaluation suggested by the ACC/AHA/ESC guidelines is as follows [6]. History and physical examination The purpose of the history and physic al examination is to define symptoms associated with AF; the c linical type or "pattern" discussed above; the onset or
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date of disc overy of the AF; the frequenc y and duration of AF episodes; any precipitating c auses and modes of termination of AF; the response to drug therapy; and the presence of heart disease or potentially reversible causes (eg, hyperthyroidism). (See "Epidemiology of and risk factors for atrial fibrillation".) The frequenc y and duration of AF episodes are primarily determined from the history. Symptoms that c an occ ur include palpitations, weakness, dizziness, reduc ed exerc ise c apac ity, and dyspnea. More serious symptoms are generally related to the presenc e and severity of underlying heart disease and include angina and manifestations related to heart failure or hypotension. Many episodes of AF are asymptomatic . Continuous monitoring studies have shown that approximately 90 perc ent of patients have rec urrent episodes of AF [7]. However, up to 90 perc ent of episodes are not rec ognized by the patient [8] and asymptomatic episodes lasting more than 48 hours are not uncommon, occ urring in 17 perc ent of patients in a report using c ontinuous monitoring [7]. The latter study also showed that 40 perc ent of patients had episodes of AF-like symptoms in the absenc e of AF [7]. (See "Paroxysmal atrial fibrillation".) Electrocardiogram The electrocardiogram is used to verify the presenc e of AF; identify left ventric ular hypertrophy, preexc itation, bundle branch bloc k, or prior MI; define P wave duration and morphology as well as other atrial arrhythmias on earlier ECGs; and to measure important intervals such as the RR, QRS, and QT. (See "Elec troc ardiographic and elec trophysiologic features of atrial fibrillation".) It is important to recognize that there are a number of potential pitfalls in the electrocardiographic diagnosis of AF. Errors in the diagnosis of AF are espec ially c ommon with c omputerized ECG interpretation and in patients who are c ontinuously or intermittently paced. (See "Elec troc ardiographic and elec trophysiologic features of atrial fibrillation", sec tion on 'Pitfalls'.) Chest x-ray When c linical findings suggest, the chest x-ray may be useful in assessing the lungs, vasculature, and c ardiac outline. Echocardiogram The transthorac ic echocardiogram is performed to evaluate the size of the right and left atria and the size and func tion of the right and left ventricles; to detec t possible valvular heart disease, left ventric ular hypertrophy, and peric ardial disease; and to assess peak right ventricular pressure. It may also identify a left atrial thrombus, although the sensitivity is low. Transesophageal ec hoc ardiography is muc h more sensitive for identifying thrombi in the left atrium or left atrial appendage and c an be used to determine the need for three to four weeks of anticoagulation prior to c ardioversion. (See 'Antic oagulation during restoration of NSR' below and "Role of ec hoc ardiography in atrial fibrillation".) Assessment for hyperthyroidism The frequenc y of both clinic al and subc linical hyperthyroidism in AF was illustrated in a review of 726 patients with recent onset AF [9]. A low serum thyroid-stimulating hormone (TSH) value was found in 5.4 perc ent; only 1 percent were c onfirmed to have c linic al hyperthyroidism. (See "Epidemiology of and risk fac tors for atrial fibrillation", sec tion on 'Hyperthyroidism'.) Thus, subc linic al hyperthyroidism is sufficiently c ommon that measurement of serum TSH and free T4 is indic ated in all patients with a first episode of AF, when the ventric ular response to AF is diffic ult to control, or when AF rec urs unexpectedly after cardioversion. Patients with low values (<0.5 mU/L with the newer sensitive assays) and normal serum free T4 probably have subc linic al hyperthyroidism. (See "Subc linic al hyperthyroidism".) Additional testing Exercise testing is often used to assess the adequacy of rate c ontrol in permanent AF, to reproduc e exerc ise-induc ed AF, and to evaluate for associated ischemic heart disease (which is not a common c ause of AF). Identifying underlying c oronary disease is partic ularly important if a c lass IC antiarrhythmic drug is used since, as demonstrated in the CAST trial, these drugs may have a significant proarrhythmic effect and inc rease mortality in
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suc h patients (figure 2) [10]. Holter monitoring or event recorders are used to identify the arrhythmia if it is intermittent and not c aptured on routine electrocardiography. Ambulatory monitoring is also used to identify triggering events and to evaluate rate c ontrol under c onditions of routine activity. (See "Ambulatory monitoring in the assessment of c ardiac arrhythmias".) Electrophysiologic studies may be required in certain settings. These inc lude patients with wide QRS c omplex tac hycardia or a possible predisposing arrhythmia suc h as atrial flutter or a paroxysmal supraventricular tachycardia. EP studies are also performed as part of AV nodal or focal arrhythmia ablation. (See "Invasive cardiac electrophysiology studies: Tac hyarrhythmias" and "Radiofrequenc y c atheter ablation to prevent rec urrent atrial fibrillation".) GENERAL TREATMENT ISSUES There are four main issues that must be addressed in the treatment of AF: Rhythm control, whic h consists of reversion to normal sinus rhythm (NSR) followed by maintenanc e of NSR Rate c ontrol, whic h c onsists of the administration of medic ations to control the ventricular rate in patients with c hronic AF Choosing between rhythm and rate control Prevention of systemic embolization The choic e of therapy is influenc ed by whether the AF is rec urrent paroxysmal, rec urrent persistent, or permanent (c hronic) as defined above. In addition, patient education and input are c ritical given the potential morbidity assoc iated with both AF and its treatment. As an example, the c hoic e between rhythm control and rate c ontrol may be based in part upon the patient's preference. The following disc ussion will foc us on two areas: a brief summary of these four treatment issues, each of whic h is disc ussed in detail separately; and the presentation and management of recent onset AF. The recommendations are generally in agreement with guidelines published in 2001 by a Task Force of the ACC/AHA/European Soc iety of Cardiology (ESC) [6] and with a c linical guideline based upon a systematic review of randomized c ontrolled trials published in 2003 by the American Ac ademy of Family Physic ians and the American College of Physicians (AAFP/ACP) [11,12]. The AAFP/ACP guideline on first-detec ted AF reac hed the following major conclusions; eac h of these issues is disc ussed in detail below [11,12]: Rate c ontrol with c hronic antic oagulation is rec ommended for the majority of patients with AF. Beta blockers (eg, atenolol or metoprolol) and the c alcium c hannel bloc kers diltiazem and verapamil are recommended for rate control at both rest and exercise. In contrast, digoxin is not effective during exercise. As a result, it is mainly used in patients with heart failure (in whom it also treats the underlying disease), in those who are not physic ally ac tive (eg, many elderly patients), or as a second-line agent. Antic oagulation should be ac hieved with adjusted-dose warfarin unless the patient is considered at low embolic risk or has a contraindic ation. Aspirin may be used in suc h patients although the evidenc e of benefit is not c onc lusive (odds ratio 0.68 c ompared to plac ebo, 95% CI 0.46-1.02, p = 0.06) (table 1). When rhythm control is c hosen, both DC and pharmac ologic c ardioversion are appropriate options (table 2 and table 3A-B). To prevent dislodgment of preexisting thrombi and to allow suc h thrombi to organize, warfarin therapy should be given for three to four weeks prior to cardioversion unless transesophageal ec hoc ardiography demonstrates no left atrial
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or left atrial appendage thrombi. Antic oagulation with either approac h is c ontinued for at least one month after c ardioversion to prevent de novo thrombus formation that may result from a transient period of "atrial stunning." (see "Anticoagulation prior to and after restoration of sinus rhythm in atrial fibrillation"). After c ardioversion, antiarrhythmic drugs to maintain sinus rhythm are not recommended, since the risks outweigh the benefits, exc ept for patients with frequent symptomatic rec urrenc es or those with persistent symptoms despite adequate rate control that interfere with the quality of life. Recommended drugs for maintenanc e of sinus rhythm vary with patient c harac teristic s. As an example, flec ainide or propafenone is recommended in patients with no or minimal heart disease, while amiodarone or dofetilide is preferred in patients with heart failure (algorithm 1). Rhythm control Reversion to NSR There are two standard approac hes to c onverting AF to sinus rhythm: sync hronized external DC c ardioversion and pharmacologic cardioversion. The timing of attempted c ardioversion is influenced by the duration of AF. In particular, patients with AF of more than 48 hours duration, of unknown duration, or of less than 48 hours duration in the presenc e of mitral stenosis or a history of thromboembolism may have atrial thrombi that can embolize. In suc h patients, c ardioversion should be delayed until the patient has been anticoagulated at appropriate levels (INR 2.0 to 3.0) for three to four weeks, or shorter term anticoagulation if screening transesophageal echocardiography has excluded atrial and atrial appendage thrombi (table 4). (See 'Antic oagulation during restoration of NSR' below.) DC c ardioversion is indicated in patients who are hemodynamic ally unstable, a setting in which the AF is typic ally of short duration. In stable patients in whom spontaneous reversion due to c orrection of an underlying disease is not likely, either DC or pharmacologic cardioversion c an be performed (table 2 and table 3A-B). Elec trical cardioversion is usually preferred because of greater effic ac y and a low risk of proarrhythmia. The overall suc c ess rate (at any level of energy) of elec trical cardioversion for AF is 75 to 93 perc ent and is related inversely both to the duration of AF and to left atrial size [13]. (See "Restoration of sinus rhythm in atrial fibrillation".) A number of antiarrhythmic drugs are more effective than placebo, c onverting 30 to 60 percent of patients [14]. Evidence of efficac y from randomized trials is best established for ibutilide, flecainide, dofetilide, propafenone, and amiodarone (table 3A-B and table 5) [12]. The 2006 ACC/AHA/ESC guidelines concluded that evidenc e for benefit from spec ific antiarrhythmic drugs varies with the duration of AF: dofetilide, flec ainide, ibutilide, propafenone, or, to a lesser degree, amiodarone (unless the patient has left ventric ular dysfunc tion or heart failure) if 7 days duration; and dofetilide or, to a lesser degree, amiodarone or ibutilide if AF is more prolonged [6]. Similar drugs were rec ommended by the AHA in collaboration with the International Liaison Committee on Resuscitation (ILCOR) (table 6A-B) [15]. (See "Restoration of sinus rhythm in atrial fibrillation".) Rate c ontrol with an atrioventricular (AV) nodal bloc ker (beta blocker, diltiazem, or verapamil) or, if the patient has heart failure or hypotension, digoxin should be attained before instituting a c lass IA or IC drug bec ause of possible recurrenc e with atrial flutter that can be assoc iated with 1:1 c onduction through the AV node and a very rapid ventric ular response. Maintenance of NSR Only 20 to 30 percent of patients who are suc cessfully c ardioverted maintain NSR for more than one year without c hronic antiarrhythmic therapy [2,3,5]. This is more likely to occ ur in patients with AF for less than one year, no enlargement of the left atrium (ie, 4.0 c m), and a reversible c ause of AF suc h as hyperthyroidism, peric arditis, pulmonary embolism, or c ardiac surgery [2,16]. It has been thought that the drugs that are most likely to maintain NSR suppress triggering ec topic beats and arrhythmias, and affec t atrial elec trophysiologic properties to diminish the
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likelihood of AF. There is therefore a strong rationale for prophylac tic antiarrhythmic drug therapy in patients who have a moderate to high risk for rec urrenc e, provided that it is effec tive and that both toxicity and proarrhythmic effects are low (table 7A-C). As mentioned above, the AAFP/ACP clinic al guideline concluded that the risks generally outweigh the benefits of maintenanc e of antiarrhythmic drug therapy, except in patients with persistent symptoms on a rate control regimen [11,12]. Maintenance therapy may also be important for patients with frequent rec urrenc es that are assoc iated with more severe manifestations, suc h as angina, hypotension, or heart failure. (See 'Rhythm control versus rate c ontrol' below.) The c hoic e among the different drugs, as recommended by the 2006 ACC/AHA/ESC guidelines, varies with the c linic al setting [6]. As examples, flecainide or propafenone is preferred in patients with no or minimal heart disease, while amiodarone or dofetilide is preferred in patients with a reduc ed left ventricular (LV) ejec tion fraction or heart failure (algorithm 1). Conc urrent administration of an AV nodal blocker is indic ated in patients who have demonstrated a moderate to rapid ventricular response to AF. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Rec ommendations".) There is inc reasing evidenc e that amiodarone is signific antly more effec tive for maintenanc e of sinus rhythm than other antiarrhythmic drugs. In two randomized trials Canadian Trial of Atrial Fibrillation (CTAF) and SAFE-T and a substudy analysis from the rhythm control arm in the AFFIRM trial, patients treated with amiodarone had a greater likelihood of being free from recurrent AF at 12 to 16 months than those treated with sotalol (52 to 65 versus 32 to 38 perc ent) or c lass I antiarrhythmic drugs (62 to 65 versus 23 to 37 perc ent) (figure 3 and figure 4) [17-19]. In SAFE-T, sotalol had similar effic acy to amiodarone in the subgroup of patients with c oronary heart disease (figure 5) [18]. A similar subgroup analysis was not made in CTAF or AFFIRM. Despite these benefits, the ACC/AHA/ESC guidelines c onc luded that bec ause of the c onc erns about toxicity, the use of amiodarone as a first-line therapy for maintenance of NSR should be reserved for patients with heart failure, moderate-to-severe systolic dysfunc tion, or hypertension with substantial left ventric ular hypertrophy [6]. (See "Major side effects of amiodarone" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", sec tion on 'Selec ting an antiarrhythmic drug'.) Hospitalization Most patients are hospitalized for c ardioversion (inc luding pharmac ologic ) and, when a rhythm c ontrol strategy is c hosen, for the initiation of maintenance antiarrhythmic drug therapy. The primary indication for hospitalization is observation for proarrhythmia and bradyarrhythmias. There are, however, some settings in whic h outpatient initiation of therapy c an be safely performed. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Rec ommendations", section on 'Inpatient versus outpatient initiation' and "Restoration of sinus rhythm in atrial fibrillation".) A separate issue is hospitalization for new onset AF. (See "Management of new onset atrial fibrillation", sec tion on 'Indications for hospitalization'.) Rate control in chronic AF There are two important reasons to prevent a rapid ventricular response in patients with AF: avoidance of hemodynamic instability and/or symptoms suc h as palpitations, heart failure, angina, lightheadedness, and poor exerc ise c apac ity; and, over the long-term, avoidanc e of a tachycardia-mediated c ardiomyopathy. (See "Hemodynamic c onsequenc es of atrial fibrillation and c ardioversion to sinus rhythm" and "Tac hyc ardia-mediated c ardiomyopathy".) Rate c ontrol in AF is usually achieved by slowing AV nodal c onduc tion with a beta bloc ker, diltiazem, verapamil, or, in patients with heart failure or hypotension, digoxin. Amiodarone is also effec tive, although it is not used as a primary therapy for rate control (algorithm 2 and table 8AB) [2,3,6,20]. (See "Management of new onset atrial fibrillation", sec tion on 'Initial rate c ontrol with mild to moderate symptoms' and "Control of ventricular rate in atrial fibrillation:
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Pharmac ologic therapy".) Rate c ontrol should be assessed both at rest and with exertion. In the AFFIRM trial desc ribed in the next section, heart rate targets for the patients in the rate c ontrol arm included [21]: Rest heart rate 80 beats/min 24-hour Holter average 100 beats/min and no heart rate >110 perc ent of the agepredic ted maximum Heart rate 110 beats/min in six minute walk More than 80 perc ent of patients in the rate c ontrol group who remained in AF had adequate heart rate c ontrol, almost all with pharmac ologic therapy. An alternative method to assess rate c ontrol during exercise is submaximal or maximal exercise ECG testing [6]. However, these recommendations may be burdensome to perform in all patients in clinic al prac tice. Our approac h is related to the kind of exercise the patient might do at home. Thus, for young active patients, we recommend either an exerc ise ECG test or a Holter during exercise. For older or sedentary patients, walking briskly around the office or up stairs may be sufficient. An essential c omponent of rate control over time is the absence of symptoms during normal ac tivities or exerc ise. Rhythm control versus rate control In the past, many physic ians preferred rhythm to rate c ontrol. Reversion of AF and maintenanc e of NSR restores normal hemodynamics and had been thought to reduc e the frequency of embolism. However, several major clinic al trials (eg, AFFIRM and RACE) that c ompared rhythm and rate c ontrol reac hed two major conclusions [21,22] (see "Rhythm c ontrol versus rate c ontrol in atrial fibrillation"): Embolic events oc cur with equal frequenc y regardless of whether a rate c ontrol or rhythm control strategy is pursued, and occ ur most often after warfarin has been stopped or when the International Normalized Ratio (INR) is subtherapeutic . Embolization with apparently succ essful rhythm c ontrol can reflec t one of two mechanisms. First, most patients treated with a rhythm c ontrol strategy have rec urrent episodes of paroxysmal AF, up to 90 percent of whic h are asymptomatic [7,8]. Even episodes lasting more than 48 hours c an be unrecognized by the patient [7]. Sec ond, other risk factors for embolization may be present when the patient is in sinus rhythm (eg, left ventric ular systolic dysfunc tion and thromboemboli or atheroemboli from c omplex aortic plaque). (See "Indic ations for anticoagulation in heart failure" and "Embolism from aortic plaque: Thromboembolism" and "Embolism from aortic plaque: Atheroembolism (c holesterol crystal embolism)".) Both studies showed an almost signific ant trend toward a lower inc idence of the primary end point with rate c ontrol (hazard ratio 0.87 for mortality in AFFIRM and 0.73 for a composite end point in RACE) (figure 6 and figure 7). There was no differenc e in func tional status or quality of life. These trials support the conclusion that rate c ontrol is the preferred initial approac h in most patients [11,12]. There are three primary settings in whic h a rhythm c ontrol strategy using antiarrhythmic drugs to maintain sinus rhythm should be considered [11]: Persistent symptoms (palpitations, dyspnea, lightheadedness, angina, presyncope, and heart failure) despite adequate rate c ontrol. (See "Hemodynamic c onsequences of atrial fibrillation and c ardioversion to sinus rhythm".) An inability to attain adequate rate c ontrol Patient preferenc e In addition, we c onsider cardioversion to sinus rhythm in most patients, partic ularly younger
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patients, with a first detected episode of AF in whom the arrhythmia is of recent onset and the risk for rec urrenc e appears to be low as defined above. However, maintenanc e antiarrhythmic drug therapy is not routinely used after cardioversion in patients with newly detec ted AF [12]. These issues are disc ussed in detail separately. (See "Rhythm c ontrol versus rate c ontrol in atrial fibrillation", sec tion on 'Choic e of therapy'.) Nonpharmacologic approaches The medic al approac hes to either rate or rhythm c ontrol desc ribed above are not always effective. These observations provide the basis for inc reasing interest in nonpharmac ologic approac hes to AF management. The major nonpharmac ologic options are mentioned briefly here and are disc ussed in detail elsewhere. Rhythm control There are several alternative methods to maintain NSR in patients who are refrac tory to c onventional therapy, inc luding surgery, radiofrequenc y c atheter ablation, and pacemakers. Of these approac hes, pulmonary vein isolation using radiofrequenc y c atheter ablation is the subjec t of increasing interest and investigation. (See "Radiofrequency c atheter ablation to prevent rec urrent atrial fibrillation" and "The role of pac emakers in the prevention of atrial fibrillation" and "Surgic al approac hes to prevent recurrent atrial fibrillation".) Rate control Radiofrequency AV nodal-His bundle ablation with permanent pacemaker placement or AV nodal conduction modific ation are nonpharmacologic therapies for ac hieving rate c ontrol in patients who do not respond to pharmac ologic therapy. (See "Control of ventricular rate in atrial fibrillation: Nonpharmacologic therapy".) LAA occlusion or ligation Sinc e the vast majority to thrombi in nonvalvular AF arise within or involve the left atrial appendage (LAA), the LAA is occ luded at the time of surgery in patients who undergo c ardiac surgery for other reasons. Perc utaneous approac hes have also been evaluated. (See "Nonpharmac ologic therapy to prevent embolization in patients with atrial fibrillation".) Prevention of systemic embolization Anticoagulation to prevent systemic embolization is required in two settings: during c ardioversion to sinus rhythm and in patients with c hronic or paroxysmal AF. Anticoagulation during restoration of NSR Issues related to antic oagulation during restoration of NSR are discussed in detail separately. What follows is a summary of the major options. (See "Antic oagulation prior to and after restoration of sinus rhythm in atrial fibrillation".) AF for more than 48 hours or unknown duration Based upon observational studies, guidelines published in 2006 by the ACC/AHA/ESC and in 2008 by the American College of Chest Physic ians (ACCP) strongly rec ommended that outpatients without a contraindic ation to warfarin who have been in AF for more than 48 hours should receive three to four weeks of warfarin prior to and after cardioversion (table 4) [6,23]. This approach is also rec ommended for patients with AF who have mitral stenosis, prior thromboembolism, or when AF is of unknown duration, as in an asymptomatic patient. The rationale for antic oagulation prior to cardioversion is that over 85 percent of left atrial thrombi resolve after four weeks of warfarin therapy [24]. The recommended target INR is 2.5 (range 2.0 to 3.0) (table 4) [6,23]. It has been suggested that it may be prudent to aim for an INR 2.5 before c ardioversion to provide the greatest protec tion against embolic events [25]. Probably more important is to doc ument that the INR has c onsistently been 2.0 in the weeks before cardioversion [26]. An alternative approach that eliminates the need for prolonged antic oagulation prior to c ardioversion is sc reening transesophageal echocardiography to doc ument the absenc e of atrial thrombi. This approach should be partic ularly c onsidered in patients who require hospitalization, have an inc reased risk of hemorrhagic c omplic ations during prolonged warfarin therapy, or are not likely to tolerate AF despite adequate rate slowing. The AAFP/ACP c linical guideline
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c onc luded that both the conventional approac h with three to four weeks of prec ardioversion anticoagulation and the TEE-guided approach were appropriate management strategies [11,12]. After c ardioversion, it is recommended that warfarin therapy be continued for at least four weeks with a target INR of 2.5 (range 2.0 to 3.0) (table 4) [23]. However, this rec ommendation only deals with protection from embolic events related to the c ardioversion period. However, as noted above, over one-half of patients who are c ardioverted and then maintained on antiarrhythmic drugs develop recurrent AF. Furthermore, in the AFFIRM and RACE trials noted above, the embolic risk was similar with rhythm and rate c ontrol [21,22]. Thus, the long-term rec ommendations for patients who have been cardioverted to NSR but are at high risk for thromboembolism are similar to those in patients with chronic AF, even though the patients are in sinus rhythm. We prefer the CHADS2 sc ore for estimation of the risk of ischemic stroke or peripheral embolization (table 9). (See 'Antic oagulation in chronic AF' below.) The rationale for chronic antic oagulation is twofold: Suc h patients are likely to have recurrent episodes of AF, up to 90 perc ent of whic h are asymptomatic [8], inc luding some episodes that last more than 48 hours [7]. During these asymptomatic periods of AF, thrombi may form that c an cause c linic al thromboembolism. Patients with AF that is nonvalvular and not due to a reversible disease (eg, hyperthyroidism, cardiac surgery) often have predisposing fac tors for embolism even when they are in sinus rhythm. These inc lude c omplex aortic plaque and left ventric ular systolic dysfunc tion. (See "Indic ations for anticoagulation in heart failure" and "Embolism from aortic plaque: Thromboembolism".) AF for less than 48 hours A different approach with respec t to antic oagulation c an be used in low risk patients (no mitral valve disease, severe left ventricular dysfunction, nor history of prior thromboembolism) in whom there is reasonable certainty that AF has been present for less than 48 hours. Suc h patients have a low risk of c linic al thromboembolism if converted early (0.8 perc ent in one study), even without screening TEE [27]. (See "Antic oagulation prior to and after restoration of sinus rhythm in atrial fibrillation", sec tion on 'AF of less than 48 hours duration'.) The ACC/AHA/ESC guidelines, ILCOR, and the ACCP Consensus Conference do not recommend long-term anticoagulation prior to c ardioversion in suc h patients, but do rec ommend heparin use at presentation and during the pericardioversion period [6,15,23]. We also ac utely antic oagulate with intravenous heparin if the patient is admitted to the hospital for a c onc urrent problem that might delay c ardioversion. (See "Management of new onset atrial fibrillation", section on 'Indic ations for hospitalization'.) The optimal therapy after c ardioversion in this group is unc ertain. The ACCP Consensus Conferenc e rec ommends oral anticoagulation for four weeks for all patients after cardioversion [23]. Our current prac tic e is to administer aspirin for a first episode of AF that c onverts spontaneously and warfarin for at least four weeks to all other patients. Aspirin should not be c onsidered in patients with AF of less than 48 hours duration if there is assoc iated rheumatic mitral valve disease, severe left ventricular dysfunc tion, or prior thromboembolism. Such patients should be treated the same as patients with AF of longer duration: one month of oral anticoagulation with warfarin or shorter term antic oagulation with screening TEE prior to elec tive elec trical or pharmacologic c ardioversion followed by prolonged warfarin therapy after c ardioversion. (See "Management of new onset atrial fibrillation", sec tion on 'Role of TEE'.) Anticoagulation in chronic AF Issues related to antic oagulation in patients with chronic AF or paroxysmal AF are disc ussed in detail separately. What follows is a summary of the major options. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".)
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The inc idence of stroke associated with AF is 3 to 5 perc ent per year in the absenc e of anticoagulation; compared with the general population, AF signific antly inc reases the risk of stroke (relative risk 2.4 in men and 3.0 in women) [28,29]. However, the risk varies markedly among patients. The inc idence of stroke is relatively low in patients with AF who are under age 75 and have no risk factors. The prevalence of stroke assoc iated with AF inc reases strikingly over age 75 and with other risk fac tors inc luding heart failure, hypertension, diabetes, or a previous stroke or peripheral embolic event (table 9). The risk appears to be equivalent in chronic and paroxysmal AF (figure 8) [30-32]. (See "Paroxysmal atrial fibrillation".) In addition to the risk of stroke, AF is associated with more severe strokes and "longer" transient ischemic attac ks than emboli from c arotid disease, presumably due to embolization of larger partic les in AF [33,34]. This was illustrated in a report comparing ischemic brain events in patients with AF and those with carotid disease in two major trials, the ratio of hemispheric events to retinal events was 25:1 with AF c ompared to 2:1 with c arotid disease [33]. The c hoic e of therapy (antic oagulant versus aspirin) varies with the estimated risk of isc hemic stroke or peripheral embolization (the latter ac c ounts for about 6 percent of embolic events) [35]. Although a number of risk stratific ation models are available for patients with c hronic AF (table 10 and table 11), we believe the CHADS2 sc ore is currently the best validated and most c linically useful (table 9) [35-37]. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".) Patients with a CHADS2 sc ore of 0 are at low risk for ischemic stroke or peripheral embolization (0.5 percent per year in the absence of antic oagulant therapy) and can be managed with aspirin. Patients with a CHADS2 score 3 are at high risk (5.3 to 6.9 percent per year) and should, in the absenc e of a c ontraindication, be treated with antic oagulant therapy. Patients with a CHADS2 sc ore of 1 or 2 are at intermediate risk (1.5 to 2.5 perc ent per year). In this group, the choice between anticoagulant therapy and aspirin will depend upon many factors, including patient preferenc e. One exception in the intermediate risk category is that most experts would c onsider patients with a prior isc hemic stroke, transient ischemic attac k, or systemic embolic event to be at high risk even if they have no other risk fac tors and therefore a CHADS2 score of 2. Furthermore, the great majority of these patients have some other risk fac tor and a CHADS2 sc ore of at least 3. Antic oagulation is benefic ial in all age groups, inc luding patients over age 75 (figure 9) and when given for secondary prevention in patients with nonrheumatic AF who have had a rec ent transient isc hemic attack or minor stroke [32,38]. The true effic acy of warfarin is likely to be even higher than suggested by trial results, sinc e many of the strokes in the warfarin-treated groups oc c urred in patients who were nonc ompliant at the time of the stroke. An INR between 2.0 and 3.0 is rec ommended for most patients with AF who receive warfarin therapy (table 10) [6,23]. A higher goal (INR between 2.5 and 3.5) is reasonable for patients at partic ularly high risk for embolization (eg, prior thromboembolism, rheumatic heart disease, prosthetic heart valves). A possible exc eption to the latter rec ommendation oc curs in patients over the age of 75 who are at inc reased risk for major bleeding. A target INR of 1.8 to 2.5 may be a reasonable c ompromise between toxic ity and effic acy for this age group. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", sec tion on 'Target INR'.) Anticoagulation in paroxysmal AF The stroke risk appears to be equivalent in paroxysmal and c hronic AF (figure 8) [30-32] and, as noted in AFFIRM and RACE, equivalent with a rate c ontrol or rhythm c ontrol strategy [21,22]. Furthermore, a subset meta- analysis found
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that the reduc tion in isc hemic stroke with oral antic oagulation in patients with paroxysmal AF (1.5 versus 4.7 events per 100 patient-years, hazard ratio 0.32) was similar to that in patients with chronic AF [39]. There are at least two reasons for the risk of embolization even when sinus rhythm is present most of the time: Approximately 90 percent of patients have recurrent episodes of AF [7]. However, up to 90 percent of episodes are not recognized by the patient [8] and asymptomatic episodes lasting more than 48 hours are not unc ommon, oc curring in 17 perc ent of patients in a report using continuous monitoring [7]. Some patients have other reasons for embolic risk such as c omplex aortic plaque or left ventricular systolic dysfunc tion. (See "Indic ations for anticoagulation in heart failure" and "Embolism from aortic plaque: Thromboembolism".) The factors governing the c hoic e between antic oagulant and aspirin therapy are similar to that noted in the previous section in patients with c hronic AF. Among patients with very infrequent and short episodes of AF, any protective effect from antic oagulation may be more than offset by bleeding risk and inc onvenienc e. However, there is at present no good way to c onfidently identify these patients. (See "Paroxysmal atrial fibrillation", section on 'Chronic therapy'.) Concurrent therapy with aspirin A separate issue is the use of aspirin for secondary prevention of c ardiovasc ular disease in patients treated with antic oagulant therapy for AF. This issue is disc ussed in detail elsewhere. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation", sec tion on 'Patients with cardiovasc ular disease taking aspirin'.) Blood pressure control The PROGRESS trial demonstrated the benefit of blood pressure lowering (using perindopril-indapamide) among both hypertensive and nonhypertensive patients who had a previous stroke or transient ischemic attac k [40]. (See "Treatment of hypertension in patients who have had a stroke", sec tion on 'Long-term therapy'.) A secondary analysis from PROGRESS evaluated the effic acy of antihypertensive therapy in the subset of 476 patients with AF [41]. Perindopril-based therapy was associated with a significant 38 perc ent reduction in major vascular events and a 34 percent reduction in rec urrent stroke (13.6 versus 18.9 percent), a differenc e that was not statistically signific ant bec ause of the small number of recurrent events. The management of patients with AF who have had a stroke is disc ussed separately. (See "Stroke in patients with atrial fibrillation".) Possible role of angiotensin inhibition Although angiotensin c onverting enzyme (ACE) inhibitors and angiotensin II rec eptor bloc kers (ARBs) have not previously been c onsidered a specific therapy in patients with AF, an increasing number of observations suggest that they may prevent both new onset AF and recurrent AF. Although the data are not definitive, these drugs might be given empirically in patients with rec urrent AF, particularly if there are other indications for their use such as hypertension, heart failure, or diabetes mellitus. (See "ACE inhibitors, angiotensin rec eptor bloc kers, and atrial fibrillation".) NEW ONSET AF Most patients with new onset (ie, first episode) AF present with symptoms related to the arrhythmia. Typic al symptoms include palpitations, a sense of the heart racing, fatigue, lightheadedness, inc reased urination, or mild shortness of breath. More severe symptoms and signs inc lude dyspnea, angina, hypotension, presync ope, or infrequently sync ope. In addition, some patients present with an embolic event or the insidious onset of right-sided heart failure (as manifested by peripheral edema, weight gain, and asc ites). Exc ept for embolization, the symptoms assoc iated with new onset AF are primarily due to a rapid ventric ular response. (See "Management of new onset atrial fibrillation".) LONG-TERM OUTCOME Although the morbidity assoc iated with AF, primarily HF and stroke, is well established, it is not clear if AF itself results in excess mortality. Patients under the age of
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60 who have AF but no apparent heart disease (c alled lone AF) have been considered a group with a good prognosis [42,43]. However, AF appears to be a risk factor for increased mortality in otherwise healthy older individuals and those with coexisting c ardiovasc ular disease, an effect that appears to be more prominent in women [43-45]. This was illustrated in a report from the Framingham Heart Study in which 621 subjects between the ages of 55 and 94 who developed AF were compared to those who did not [44]. AF almost doubled the risk of death in both men and women (figure 10). After adjustment for the preexisting c ardiovasc ular diseases with whic h AF was associated, AF was still assoc iated with a signific antly inc reased risk of death (odds ratio 1.9 for women and 1.5 for men). Both HF and stroke c ontributed to the excess mortality. An inc rease in risk that was more pronounc ed in women was also noted in a 20-year follow-up of over 15,000 men and women between the ages of 45 and 64 in whic h 47 women and 53 men had AF on a single ECG at baseline [43]. The presence of AF was assoc iated with a marked increase in the risk of a c ardiovascular event (death or hospitalization) (89 versus 27 perc ent in women and 66 versus 45 percent in men) and was a signific ant independent predictor of all-c ause mortality (relative risk 2.2 in women and 1.5 in men). An association between AF and mortality was also suggested in a secondary analysis of the randomized controlled AFFIRM trial of rhythm versus rate c ontrol in AF [46]. Although outcomes were similar with both approac hes, the presenc e of sinus rhythm was assoc iated with a significant reduc tion in mortality (hazard ratio 0.53). A similar benefit from being in sinus rhythm (relative risk 0.44) was noted in the DIAMOND trial that compared dofetilide to placebo in patients with reduced left ventricular func tion [47]. The c oexistenc e of c ardiovasc ular disease and c hronic AF worsens the patient's prognosis, doubling the c ardiovascular mortality [48]: In patients with a recent MI, the development of AF increases mortality [49,50]. This effec t is primarily due to assoc iated risk factors, suc h as HF and cardiogenic shoc k, not AF itself [50,51]. The effec t of AF in the setting of HF is less c lear, sinc e published studies have yielded conflic ting results and any effec t of AF to increase mortality may have diminished with better treatment of HF. (See "Atrial fibrillation in patients with heart failure", sec tion on 'Inc idence and prevalence'.) None of these nonrandomized observations proves that AF direc tly c auses an increase in mortality, sinc e they cannot distinguish this possibility from AF being a marker of a c onfounding factor or factors that affec t survival. Gender differences The importanc e of gender differences in the presentation and treatment of AF has been evaluated in several observational studies and retrospec tive analyses [52-55]. These reports have found that women with AF tend to present at an older age and have a higher prevalenc e of stroke risk fac tors, most notably hypertension. The efficac y, safety, and use of antiarrhythmic and anticoagulation therapies have been different from men in some, but not all, reports. In one series, 900 men and women with new-onset AF who were followed for more than four years [52]. The following findings were noted: At presentation, women were older than men (65 versus 61 years) and were more likely to seek medic al advic e because of symptoms. The rate of c ardioversion and use of cardiac medic ations was the same. However, women 75 years of age were 54 perc ent less likely to receive warfarin, but were twice as likely to receive aspirin; this differenc e was seen even in those with one or more stroke risk
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fac tors. Women were more likely to have rec urrent episodes of paroxysmal AF (48 versus 31 percent at one year), but progression to permanent AF at three years was the same (19 percent). There was no sex difference in the incidenc e of stroke, MI, major bleeding, or cardiovascular death. However, among patients treated with warfarin, women were 3.4 times more likely to experienc e a major bleed than men. Another report evaluated the c omparative risk of isc hemic stroke and peripheral embolism in men and women with AF [53]. In some of the models of stroke risk developed from clinic al trials and c ommunity cohorts, but not in the CHADS2 sc ore that we recommend (table 9), female gender was an independent risk fac tor for stroke. (See "Risk of embolization in atrial fibrillation".) The c ohort inc luded 13,559 adults with nonvalvular AF. Women in this study were older, were more likely to have hypertension and prior strokes, and had higher CHADS2 sc ores (table 9). The following findings were reported: Among patients who were not treated with warfarin, women had a higher annual rate of thromboembolic events (3.5 versus 1.8 perc ent for men). In multivariate analysis that controlled for the stroke risk fac tors, women had a greater risk of thromboembolic events than men (RR = 1.6). Warfarin was at least as effective in lowering thromboembolic risk in women as it was in men (RR 0.4 for women and 0.6 for men, compared to no warfarin). Annual rates of major hemorrhage on warfarin were similar in women and men (1.1 and 1.0 percent respec tively); this is in c ontrast to the higher major bleeding rate in women noted in the previous report [52]. Thus, women in this c ohort had a greater baseline risk of thromboembolic events that persisted when controlled for a higher prevalenc e of known stroke risk fac tors. Women also had similar or greater benefit from warfarin therapy c ompared to men. Despite this risk-benefit profile, a prior report from the same c ohort noted that women were slightly less likely than men to receive warfarin therapy (OR 0.87) [54]. The risks and benefits of antiarrhythmic therapy in women were compared to men in a subset analysis from the RACE trial [55]. This trial enrolled 522 patients with persistent AF. All patients were randomly assigned to rate or rhythm c ontrol strategies. (See "Rhythm c ontrol versus rate c ontrol in atrial fibrillation", sec tion on 'RACE'.) Among the 192 women in RACE, the following findings were reported: Women were older than men (71 versus 67), and had higher rates of hypertension; in addition, women randomly assigned to rhythm c ontrol were more likely to have hypertension than those assigned to rate control. Women assigned to rhythm c ontrol were significantly more likely than men to have a severe adverse effec t of antiarrhythmic medic ations (9.3 versus 1.8 percent). This observation is c onsistent with other data supporting a greater risk of adverse events with antiarrhythmic drugs in women [56]. Women assigned to rhythm c ontrol had signific antly higher rates of c ardiovasc ular death (10.3 versus 3.2 perc ent with rate control), thromboembolic events (11.3 versus 2.1 percent), and pac emaker implantation (5.1 versus 2.1 perc ent).
uptodate.com//overview-of-the-eval
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Consistent with prior studies, women in RACE had a higher prevalenc e of known thromboembolic risk factors than men. In addition, 29 of 35 (83 perc ent) thromboembolic events in the entire RACE population oc c urred in patients who were either not taking anticoagulation therapy or had subtherapeutic anticoagulation. In summary, among AF patients treated with rhythm control, the need to continue anticoagulation and monitor for adverse reactions to antiarrhythmic drugs (eg, QT prolongation, bradyarrhythmias) are partic ularly important in women. INFORMATION FOR PATIENTS Educ ational materials on this topic are available for patients. (See "Patient information: Atrial fibrillation".) We enc ourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.c om/patients, which inc ludes this and other topic s. ACKNOWLEDGMENT We are saddened by the untimely death of Morton F Arnsdorf, MD, MACC, who passed away in June 2010. UpToDate wishes to acknowledge Dr. Arnsdorf's many c ontributions to c ardiology, in particular, his work as our Editor-in-Chief and Sec tion Editor for Cardiac Arrhythmias. Use of UpToDate is subjec t to the Subsc ription and License Agreement.
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GRAPHICS
Prevalence of atrial fibrillation with age
In a cross-sectional study of almost 1.9 million men and women, the prevalence of atrial fribillation increases with age, ranging from 0.1 for those less than 55 years of age to over 9 percent in those 85 years of age. At all ages, the prevalence is higher in men than women. Data from
Go, AS, Hylek, EM, Phillips, K, et al, JAMA 2001; 285:2370.
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Encainide and flecainide increase cardiac mortality
Results of the Cardiac Arrhythmia Suppression Trial (CAST) in patients with ventricular premature beats after myocardial infarction. Patients receiving encainide or flecainide had, when compared to those receiving placebo, a significantly lower rate of avoiding a cardiac event (death or resuscitated cardiac arrest) (left panel, p = 0.001) and a lower overall survival (right panel, p = 0.0006). The cause of death was arrhythmia or cardiac arrest. Data from Echt, DS, Liebson, PR, Mitchell, B, et al, N Engl J Med
1991; 324:781.
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Meta-analysis of randomized controlled trials of warfarin and aspirin for primary prevention of stroke in atrial fibrillation
Stroke Comparison
Odds ratio, 95% CI 0.31 (0.19 to 0.50) 0.68 (0.46 to 1.02) 0.66 (0.45 to 0.99) 0.52 (0.25 to 1.08) 0.44 (0.14 to 1.39) 1.01 (0.49 to 2.06) p value <0.001 0.06 0.04 0.08 0.16 >0.2
Major bleeding
Odds ratio, 95 percent CI 1.88 (0.88 to 4.0) 0.82 (0.37 to 1.78) 1.61 (0.75 to 3.44) 2.21 (0.67 to 7.25) 1.14 (0.55 to 2.36) 1.04 (0.43 to 2.48) p value 0.10 >0.2 >0.2 0.19 >0.2 >0.2
Conventional dose w arfarin versus placebo Aspirin versus placebo Conventional dose w arfarin versus aspirin Conventional dose warfarin versus low dose w arfarin Conventional dose warfarin versus low dose w arfarin plus aspirin Low dose w arfarin versus aspirin
NOTE: The data in this table cannot be directly applied to clinical practice (an individual patient) since the decision to use warfarin or aspirin is importantly related to a patient's estimated risk of embolic events. Adapted from McNamara, RL,
Tamariz, LJ, Segal, JB, Bass, EB, Ann Intern Med 2004; 139:1018.
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ACC/AHA/ESC guideline summary: Direct-current (DC) cardioversion of atrial fibrillation (AF) and flutter (AFl)
Class I - There is evidence and/or general agreement that immediate Rwave synchronized DC cardioversion of AF or AFl is indicated in the following settings
AF w ith a rapid ventricular response that does not respond promptly to pharmacologic measures and there is evidence of ongoing myocardial ischemia, symptomatic hypotension, angina, or heart failure. Preexcitation in the presence of very rapid tachycardia or hemodynamic instability. Unacceptable symptoms in the absence of hemodynamic instability. Repeated direct current cardioversion attempts may be made following administration of antiarrhythmic drugs for early relapse. In this category, immediate cardioversion may not be necessary.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of DC cardioversion of AF or AFl for patients in the following settings
Part of a long term management strategy. If the patient prefers, management of symptomatic or recurrent AF if used infrequently.
Class III - There is evidence and/or general agreement that DC cardioversion of AF or AFl is not useful or may be harmful to patients in the following settings and should therefore be avoided
Frequent repetition of direct current cardioversion for repeated relapses of AF after short periods of sinus rhythm in patients w ho have received procedures despite prophylactic antiarrhythmic drug treatment. Digitalis toxicity or hypokalemia, settings in w hich DC cardioversion is contraindicated. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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ACC/AHA/ESC guideline summary: Pharmacologic cardioversion of atrial fibrillation (AF)

Class I - There is evidence and/or general agreement that the following drugs are effective for cardioversion of AF
Flecainide. Dofetilide. Propafenone. Ibutilide.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following drugs for cardioversion of AF
Amiodarone, including use as an out-patient when rapid restoration of sinus rhythm does not appear to be necessary. A single oral bolus ("pill-in-the-pocket") of propafenone or flecainide in the out-patient setting in selected patients in w hom the safety and efficacy of this approach has been demonstrated in hospital and who meet the follow ing criteria:
1. The absence of sinus and atrioventricular (AV) node dysfunction, bundle branch block, QT interval prolongation, Brugada syndrome, and structural heart disease. 2. The presence of AV nodal blockade with a beta blocker or nondihydropyridine calcium channel blocker to prevent rapid AV conduction if atrial flutter occurs.
Class IIb - The weight of evidence or opinion is less well established for the usefulness of the following drugs for cardioversion of AF
Quinidine. Procainamide.
Class III - There is evidence and/or general agreement that the following drugs for cardioversion of AF are not useful or may be harmful
Digoxin. Sotalol. For out-of-hospital cardioversion, quinidine, procainamide, disopyramide, and dofetilide. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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ACC/AHA/ESC guideline summary: Recommended doses of drugs (listed alphabetically) proven effective for pharmacological cardioversion of atrial fibrillation
Drug
Amiodarone
Route of administration
Oral
Dosage
Inpatient: 1.2 to 1.8 g per day in divided dose until 10 g total, then 200 to 400 mg per day as single dose Outpatient 600 to 800 mg/day divided dose until 10 g total, then 200 to 400 mg per day maintenance
Potential adverse effects

Hypotension, bradycardia, QT prolongation, torsade de pointes (rare), GI upset, constipation, phlebitis (IV use)
Intravenous (IV)/oral
5 to 7 mg/kg over 30 to 60 min, then 1.2 to 1.8 g per day continuous IV or in divided oral doses until 10 g total, then 200 to 400 mg per day maintenance Creatinine clearance (mL/min): Greater than 60: 500 mcg BID 40 to 60: 250 mcg BID 20 to 40: 125 mcg BID Less than 20: Contraindicated QT prolongation, torsade de pointes; adjust dose for renal function, body size, and age
Dofetilide
Oral
Flecainide
Oral Intravenous
200 to 300 mg 1.5 to 3.0 m per kg over 10 to 20 min 1 mg over 10 min; repeat 1 mg when necessary 450 to 600 mg 1.5 to 2.0 mg per kg over 10 to 20 min 0.75 to 1.5 g in divided doses over 6 to 12 h, usually w ith a rate-slow ing drug
Hypotension, rapidly conducting atrial flutter QT prolongation, torsade de pointes Hypotension, rapidly conducting atrial flutter
Ibutilide Propafenone
Intravenous Oral Intravenous
Quinidine
Oral
QT prolongation, torsade de pointes, gastrointestinal upset, hypotension
Dosages given in the table may differ from those recommended by the manufacturers. Insufficient data are available on w hich to base specific recommendations for the use of one loading regimen over another for patients w ith ischemic heart disease or impaired left ventricular function, and these drugs should be used cautiously or not at all in such patients. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. J Am Coll Cardiol 2006; 48:e149.
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ACC/AHA/ESC guideline summary: Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation*
Caveats Flecainide - AVOID in patients with coronary artery disease. Propafenone - AVOID in patients with coronary artery disease; caution if hepatic impairment or if there has been intermittent atrial flutter. Sotalol - reduce dose (or avoid) in renal impairment; caution with history of bradycardia; correct hypokalemia before use. Disopyramide - avoid if prostatic symptoms present and reduce dose (or avoid) for renal impairment. Dofetilide - Reduce dose (or avoid) in renal impairment; correct hypokalemia before use. Amiodarone - consider long-term toxicity; use cautiously in bradycardia or with serious pulmonary disease. Quinidine and procainamide - not usually used for long-term therapy because of noncardiac side effects. * Within each box, the antiarrhythmic drugs are
listed alphabetically. The vertical flow represents the order of preference for each condition. From Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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ACC/AHA/ESC guideline summary: Prevention of thromboembolism in patients with atrial fibrillation (AF) undergoing cardioversion
Class I - There is evidence and/or general agreement that the following approaches are effective for the prevention of thromboembolism in patients with AF undergoing cardioversion
For AF duration of 48 hours or duration unknown, anticoagulation w ith a goal INR of 2.0 to 3.0 for at least three w eeks before and four w eeks after either electrical or pharmacologic cardioversion. For AF duration of more than 48 hours that requires immediate cardioversion due to hemodynamic instability:
1. Unfractionated heparin should be given concurrently (unless contraindicated) by an initial intravenous bolus followed by a continuous infusion at a dose adjusted to prolong the activated partial thromboplastin time to 1.5 to 2.0 times control. 2. Thereafter, oral anticoagulation with a goal INR of 2.0 to 3.0 for at least four weeks as in patients undergo elective cardioversion. 3. Limited data support the use of subcutaneous low molecular weight heparin.
For AF duration less than 48 hours associated w ith hemodynamic instability (as manifested by angina, myocardial infarction, shock, or pulmonary edema), immediate cardioversion should be performed with delay for prior initiation of anticoagulation.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following approaches for the prevention of thromboembolism in patients with AF undergoing cardioversion
During the 48 hours after the onset of AF, the need for anticoagulation before and after cardioversion may be based upon the patient's estimated risk of thromboembolism. A reasonable alternative to anticoagulation prior to cardioversion is transesophageal echocardiography to look for thrombus in the left atrium or left atrial appendage:
1. If thrombus is not identified, cardioversion is reasonable after initiation of unfractionated heparin (intravenous bolus followed by infusion at a dose adjusted to prolong the activated partial thromboplastin time to 1.5 to 2.0 times control). Limited data support the use of subcutaneous low molecular weight heparin for this indication. Heparin therapy is continued until oral anticoagulation with warfarin or other vitamin K antagonist has led to an INR 2.0. Oral anticoagulation with a goal INR of 2.0 to 3.0 is continued for a total duration of anticoagulation of at least four weeks. 2. If thrombus is present, oral anticoagulation with a goal INR of 2.0 to 3.0 for at least three weeks before and four weeks after restoration of sinus rhythm; a longer duration of anticoagulation may be appropriate even if cardioversion is successful, because the risk of thromboembolism often remains elevated.
For patients w ith atrial flutter undergoing cardioversion, anticoagulation according to the recommendations for AF. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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Pooled results of randomized controlled trials of efficacy and adverse effects of antiarrhythmic drugs for acute conversion of atrial fibrillation
Level of evidence and drug*
Ibutilide Flecainide Dofetilide Propafenone Amiodarone Quinidine
Odds ratio versus control (95% CI, number of trials)

30.7 (10.9 to 86, 4 trials) 13.2 (6.4 to 27.4, 5 trials) 6.7 (4.5 to 10.0, 6 trials) 3.9 (2.3 to 6.8, 14 trials) 3.2 (2.5 to 5.1, 15 trials) 2.9 (1.2 to 6.9, 3 trials)
Sustained ventricular arrhythmia in trials reporting side effects, percent

0 to 9 0 to 2 1 to 12 0 to 2 0 0 to 12
Statistically significant
Statistically inconclusive Disopyramide Sotalol 7.0 (0.3 to 153, 1 trial) 1.1 (0.1 to 6.9, 3 trials) Not reported 0 to 2
NOTE: The choice of drug for acute conversion cannot be determined from this table because of the absence of comparative trials and may be influenced by the choice of drug for maintenance therapy, if such therapy is to be given. Ibutilide is an exception since it is not used for maintenance therapy. Adapted from McNamara, RL,
Tamariz, LJ, Segal, JB, Bass, EB, Ann Intern Med 2004; 139:1018.
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Guidelines for the control of rate and rhythm in atrial fibrillation/flutter-I

Cardiac function preserved
Normal cardiac function Note: If AF >48 hours duration, use agents to convert rhythm with extreme caution in patients not receiving adequate anticoagulation because of possible embolic complications. Use only 1 of the following agents: Calcium channel blockers (Class 1) Beta-blockers (Class 1) Additional drugs are Class lIb recommendations (Does not apply) Consider: DC cardioversion Use only 1 of the following agents: Amiodarone (Class Ila) Ibutilide (Class Ila) Flecainide (Class Ila) Propafenone (Class Ila) Procainamide (Class Ila) Other drugs are Class IIb recommendations NO DC cardioversion! Note: Conversion of AF to NSR w ith drugs or shock may cause embolization of atrial thrombi unless patient has adequate anticoagulation. Use antiarrhythmic agents with extreme caution if AF >48 hours duration. OR Delayed cardioversion anticoagulation x3 weeks at proper levels Cardioversion, then Anticoagulation x4 w eeks more OR Early cardioversion Begin IV heparin at once TEE to exclude atrial clot THEN Cardioversion within 24 hours THEN Anticoagulation x4 more w eeks Impaired cardiac function (EF <40 percent or HF) (Does not apply) Note: If AF >48 hours duration, use agents to convert rhythm w ith extreme caution in patients not receiving adequate Consider: DC cardioversion OR Anticoagulation DC cardioversion
Impaired cardiac function EF <40 percent or HF
Duration <48 hours
Duration >48 hours or unknown
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Overview of the evaluation and manag anticoagulation because Amiodarone (Class Ilb) of possible embolic complications. Use only 1 of the following agents:
Digoxin (Class lIb) Diltiazem (Class IIb) Amiodarone (Class Ilb)
Note: may have proarrhythmic potential. The classes listed represent the AHA Class of Recommendation and not the Vaughn-Williams classification of antiarrhythmics.
W PW : Wolff-Parkinson-White syndrome; AF: atrial fibrillation; NSR: normal sinus rhythm; TEE: transesophageal echocardlogram; EF: ejection fraction. Adapted from: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: Circulation 2000 I-158.
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Guidelines for the control of rate and rhythm in atrial fibrillation/flutterII

Control rate
Cardiac function preservation WPW Note: IF AF >48 hours duration, use agents to convert rhythm w ith extreme caution in patients not receiving adequate anticoagulation because of possible embolic complications. DC cardioversion OR Primary antiarrhythmic agentsUse only 1 of the follow ing agents: Amiodarone Flecainide (Class IIb) Procainamide (Class IIb) Propafenone (Class IIb) Sotalol (Class IIb) Class III (can be harmful) Adenosine Beta-blockers Calcium blockers Digoxin Note: If AF >48 hours duration, use agents to convert rhythm w ith extreme caution in patients not receiving adequate anticoagulation because of possible embolic complications. DC cardioversion OR Amiodarone (Class IIb) DC cardioversion OR Primary antiarrhythmic agents Use only 1 of the follow ing agents: Amiodarone (Class IIb) Flecainide (Class llb) Procainamide (Class Ilb) Propafenone (Class lIb) Sotalol Class III (can be harmful) Adenosine Betablockers Calcium blockers Digoxin Anticoagulation followed by DC cardioversion Impaired cardiac function EF <40 percent of HF
Convert rhythm
Duration <48 hours Duration >48 hours or unknown
Note: Occasionally 2 of the named antiarrhythmic agents may be used, but use of these agents in combination may have proarrhythmic potential. The classes listed represent the AHA Class of Recommendation and not the Vaughn-Williams classification of antiarrhythmics. WPW: Wolff-Parkinson-White syndrome; AF: atrial
fibrillation; NSR: normal sinus rhythm; EF: ejection fraction; HF: heart failure. Adapted from: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: Circulation 2000 I-158.
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ACC/AHA/ESC guideline summary: Maintenance of sinus rhythm in atrial fibrillation (AF)

Class I - There is evidence and/or general agreement that the following approach is effective for the maintenance of sinus rhythm in patients with AF
Treatment of precipitating or reversible causes of AF before initiating therapy w ith antiarrhythmic drugs.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following approaches for the maintenance of sinus rhythm in patients with AF
Antiarrhythmic drug therapy to maintain sinus rhythm and prevent tachycardia-induced cardiomyopathy. Infrequent, well tolerated recurrent episodes of recurrent AF is reasonable as a successful outcome of antiarrhythmic drug therapy. Outpatient initiation of therapy in patients w ith no associated heart disease w hen the antiarrhythmic drug is w ell tolerated. In patients w ith lone AF and no structural heart disease, outpatient initiation of propafenone or flecainide therapy in patients with paroxysmal AF w ho are in sinus rhythm at the time of drug initiation. Sotalol in outpatients in sinus rhythm w ho have little or no heart disease, are prone to paroxysmal AF, a baseline uncorrected QT interval less than 460 msec, normal serum electrolytes, and no risk factors for class III drug-related proarrhythmia. Catheter ablation as an alternative to antiarrhythmic drug therapy to prevent recurrent AF in symptomatic patients w ith little or no left atrial enlargement.
Class III - There is evidence and/or general agreement that the following approaches are not useful or may be harmful for the maintenance of sinus rhythm in patients with AF
Use of a particular antiarrhythmic drug is not recommended in patients with w elldefined risk factors for proarrhythmia with that drug. Antiarrhythmic drug therapy is not recommended in patients with advanced sinus node disease or atrioventricular node dysfunction unless they have a functioning electronic cardiac pacemaker. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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ACC/AHA/ESC guideline summary: Typical doses of drugs (listed alphabetically) used to maintain sinus rhythm in patients with atrial fibrilation
Drug
Amiodarone
Daily dosage
100 to 400 mg
Potential adverse effects

Photosensitivity, pulmonary toxicity, polyneuropathy, gastrointestinal (GI) upset, bradycardia, torsade de pointes (rare), hepatic toxicity, thyroid dysfunction, eye complications Torsade de pointes, heart failure (HF), glaucoma, urinary retention, dry mouth Torsade de pointes Ventricular tachycardia, HF, enhanced atrioventricular (conversion to atrial flutter)
Disopyramide Dofetilide Flecainide
400 to 750 mg 500 to 1000 mcg 200 to 300 mg (AV) nodal conduction 450 to 900 mg 160 to 320 mg
Propafenone Sotalol
Ventricular tachycardia, HF, enhanced AV nodal conduction (conversion to atrial flutter) Torsade de pointes, HF, bradycardia, exacerbation of chronic obstructive or bronchospastic lung disease
The drugs and doses given here have been determined by consensus based on published studies. A loading dose of 600 mg per day is usually given for one month or 1000 mg per day over one week. Dose should be adjusted for renal function and QT interval response during in-hospital initiation phase. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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Types of proarrhythmia during treatment with antiarrhythmic drugs (AADs) for atrial fibrillation or flutter according to the Vaughan Williams Classification
Ventricular proarrhythmia
Torsade de pointes (Vaughan Williams class IA and type III drugs) Sustained monomorphic ventricular tachycardia (usually class IC drugs) Sustained polymorphic ventricular tachycardia/ventricular fibrillation without long QT interval (class IA, IC, and III drugs)
Atrial proarrhythmia
Provocation of recurrence (probably class IA, IC, and III drugs) Conversion of atrial fibrillation (AF) to flutter (usually class IC drugs) Increase of defibrillation threshold (a potential problem with class IC drugs)
Abnormalities of conduction or impulse formation

Accelerate ventricular rate during AF (class IA and type IC drugs) Accelerate conduction over accessory pathway (digoxin, type IV drugs) Sinus node dysfunction, atrioventricular block (almost all drugs)
Vaughan Williams classification of AADs used for the treatment of atrial fibrillation or flutter
Class IA - Disopyramide, procainamide, quinidine Class IC - Flecainide, propafenone Class III - Amiodarone, dofetilide, ibutilide, sotalol Class IV - Nondihydropyridine calcium channel blockers (diltiazem and verapamil) Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149. .
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The rate of recurrent atrial fibrillation is lowest with amiodarone
The Canadian Trial of Atrial Fibrillation randomized 403 patients with at least one episode of atrial fibrillation (AF) during the prior six months to lowdose amiodarone, propafenone, or sotalol. After a mean follow-up of 16 months, the likelihood of being free from recurrent AF was highest with amiodarone (65 versus 37 percent for sotalol and propafenone) and the median time to recurrence was longer (>468 versus 98 days). Data from Roy,
D, Talajic, M, Dorian, P, et al. N Engl J Med 2000; 342:913.
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Amiodarone for maintenance of sinus rhythm in SAFET
In the maintenance phase of the SAFE-T trial, 665 patients with AF who had converted to sinus rhythm were maintained on amiodarone, sotalol, or placebo. The rate of maintenance of sinus rhythm was significantly higher at one year with amiodarone than sotalol or placebo and with sotalol than placebo (65 versus 40 and 18 percent on treatment received analysis). Reproduced with permission from: Singh, BN, Singh, SN,
Reda, DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005; 352:1861. Copyright 2005 Massachusetts Medical Society.
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Amiodarone and sotalol in ischemic heart disease in SAFE-T
In the maintenance phase of the SAFE-T trial, 665 patients with AF who had converted to sinus rhythm were maintained on amiodarone, sotalol, or placebo. Among the approximately 25 percent of patients with ischemic heart disease, the likelihood of remaining in sinus rhythm with amiodarone or sotalol was not significantly different. Reproduced with permission
from: Singh, BN, Singh, SN, Reda, DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005; 352:1861. Copyright 2005 Massachusetts Medical Society.
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Management algorithm of permanent atrial fibrillation - rate control
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ACC/AHA/ESC guideline summary: Pharmacologic rate control during atrial fibrillation (AF)
Class I - There is evidence and/or general agreement that the following approaches are effective for rate control in patients with AF
The heart rate should be measured at rest and during exercise, particularly in patients with symptoms related to AF with exertion. An oral beta blocker or nondihydropyridine calcium channel blocker in most patients with persistent or permanent AF. Oral digoxin in patients w ith heart failure or asymptomatic left ventricular dysfunction and in patients who are sedentary. Intravenous therapy in the follow ing acute settings in the absence of preexcitation:
1. Intravenous beta blockers or nondihydropyridine calcium channel blocker, with caution in patients with hypotension or heart failure. 2. Intravenous digoxin or amiodarone in patients with heart failure.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following approaches in patients with AF
If monotherapy is ineffective, digoxin plus a beta blocker or nondihydropyridine calcium channel blocker. When medical therapy is ineffective or not tolerated, ablation of the atrioventricular (AV) node or accessory pathway. Intravenous therapy in the follow ing acute settings:
1. Intravenous amiodarone when the intravenous drugs cited above are ineffective or contraindicated. 2. Intravenous procainamide or ibutilide in patients with an accessory pathway in whom electrical cardioversion is not necessary.
Class IIb - The weight of evidence or opinion is less well established for the usefulness of the following approaches in patients with AF
Oral amiodarone when combination therapy w ith beta blockers, nondihydropyridine calcium channel blockers, and/or digoxin do not adequately control the ventricular rate at rest and during exercise. Intravenous procainamide, disopyramide, ibutilide, or amiodarone w ith conduction over an accessory pathway in stable patients. Catheter ablation of the AV node w hen the ventricular rate cannot be controlled with the above oral drugs or tachycardia-induced cardiomyopathy is suspected.
Class III - There is evidence and/or general agreement that the following approaches are not useful or may be harmful in patients with AF
Oral digoxin as the sole drug in paroxysmal AF. Catheter ablation of the AV node as a first-line therapy. Intravenous nondihydropyridine calcium channel blocker may w orsen decompensated heart failure. Because they may paradoxically increase the ventricular rate, intravenous digoxin or nondihydropyridine calcium channel blocker in patients w ith a preexcitation syndrome. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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ACC/AHA/ESC guideline summary: Intravenous pharmacologic agents for acute heart rate control in patients with atrial fibrillation (AF) according to presence or absence of accessory pathway or heart failure (HF)
Drug* Loading dose Onset Maintenance dose Major side effects
There is evidence and/or general agreement that the following drugs are effective for acute heart rate control in patients with AF who do NOT have an accessory pathway or HF Esmolol* 0.5 mg/kg over 1 min 5 min 0.06 to 0.2 mg/kg per min Not applicable (NA) NA Hypotension, heart block, bradycardia, asthma, HF Hypotension, heart block bradycardia, asthma, HF Hypotension, heart block, bradycardia, asthma, HF Hypotension, heart block, HF Hypotension, heart block, HF
Metoprolol
2.5 to 5 mg IV bolus over 2 min; up to 3 doses 0.15 mg/kg
5 min
Propranolol
5 min
Diltiazem Verapamil
0.25 mg/kg IV over 2 min 0.075 to 0.15 mg/kg over 2 min
2 to 7 min 3 to 5 min
5 to 15 mg/h infusion NA
The weight of evidence or opinion is in favor of the efficacy of following drug for acute heart rate control in patients with AF who have an accessory pathway Amiodarone 150 mg over 10 min Days 0.5 to 1.0 mg/min See "Major side effects of amiodarone"
The following drugs can be used for acute heart rate control in patients with AF who have HF but not an accessory pathway# Digoxin 0.25 mg every 2 h, up to 1.5 mg 150 mg over 10 min 2h 0.125 to 0.25 mg daily 0.5 to 1.0 mg/min Digitalis toxicity, heart block, bradycardia See "Major side effects of amiodarone"
Amiodarone
Days
* Onset of action is variable and some effect occurs earlier. Representative of the types of beta blockers that could be used but similar drugs could be given for this indication in appropriate doses. Amiodarone can be useful when other measures are unsuccessful or contraindicated. For patients w ith an accessory pathw ay, intravenous amiodarone can be given if the rhythm cannot be converted or ablated and rate control is needed. # There is evidence and/or general agreement that digoxin is effective in patients w ith HF but not an accessory pathway, and evidence is in favor of efficacy of amiodarone in this setting. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006; 48:e149.
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Rate control versus rhythm control in AFFIRM
Results of the AFFIRM trial in which 4060 patients with atrial fibrillation (AF) that was likely to be recurrent were randomly assigned to rhythm or rate control. The primary end point was overall mortality. There was an almost significant trend toward lower mortality with rate control (21.3 versus 23.8 percent, hazard ratio 0.87, 95 percent CI 0.75 to 1.01). Data from Wyse, DG, Waldo, AL,
DiMarco, JP, et al. N Engl J Med 2002; 347:1825.
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Rate control versus rhythm control in RACE
Results of the RACE trial in which 522 patients with recurrent persistent atrial fibrillation (AF) were randomly assigned to rhythm or rate control. The primary end point was a composite of cardiovascular death, heart failure, thromboembolism, bleeding, pacemaker placement, and antiarrhythmic drug side effects. There was an almost significant trend toward a lower incidence of the primary end point with rate control (17.2 versus 22.6 percent with rhythm control, hazard ratio 0.73, 90 percent CI 0.53 to 1.01). Data from Van Gelder, IC, Hagens, VE,
Bosker, HA, et al. N Engl J Med 2002; 347:1834.
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CHADS2 score, thromboembolic risk, and effect of warfarin in 11,526 patients with nonvalvular atrial fibrillation and no contraindications to warfarin therapy
Clinical parameter
Congestive heart failure (any history) Hypertension (prior history) Age 75 years
Points
1 1 1 1 2
Diabetes mellitus Secondary prevention in patients with a prior ischemic stroke or a transient ischemic attack; most experts also include patients with a systemic embolic event
CHADS2 score
0 1 2 3 4 5 or 6 0.25 0.72 1.27 2.20 2.35 4.60
Events per 100 person-years*

Warfarin 0.49 1.52 2.50 5.27 6.02 6.88 No warfarin
NNT
417 125 81 33 27 44
NNT: number needed to treat to prevent one stroke per year with warfarin. * The CHADS2 score estimates the risk of stroke, w hich is defined as focal neurologic signs or symptoms that persist for more than 24 hours and that cannot be explained by hemorrhage, trauma, or other factors, or peripheral embolization, which is much less common. Transient ischemic attacks are not included. All differences betw een w arfarin and no warfarin groups are statistically significant except for a trend w ith a CHADS2 score of 0. Patients are considered to be at low risk w ith a score of 0, at intermediate risk with a score of 1 or 2, and at high risk with a score 3. One exception is that most experts w ould consider patients with a prior ischemic stroke, transient ischemic attack, or systemic embolic event to be at high risk even if they had no other risk factors and therefore a score of 2. How ever, the great majority of these patients have some other risk factor and a score of at least 3. Data from Go, AS, Hylek, EM, Chang, Y, et al, JAMA 2003; 290:2685; and CHADS2 score from Gage, BF, Waterman, AD, Shannon, W, JAMA 2001; 285:2864.
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Rate of ischemic stroke is related to risk category
The incidence of a stroke in patients with either intermittent or sustained atrial fibrillation (AF) is related to risk category; the patients were treated with aspirin and followed for a mean of two years. Among those with intermittent AF, 24 percent were high risk, 32 percent are moderate risk and 43 percent are low risk; among those with sustaind AF, the respective values were 30, 34, and 36 percent. The stroke risk was similar in patients with intermittent and sustained AF. High risk: any of the following - age
>75 and hypertension, age >75 and female, systolic BP >160 mmHg, prior stroke or transient ischemic attack; Moderate risk: either of hypertension and age 75 or diabetes and no high risk features; Low risk: no moderate or high risk features. Data from Hart, RG, Pearce, LA, Rothbart, RM, et al, J Am Coll Cardiol 2000; 35:183.
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ACC/AHA/ESC guideline summary: Chronic antithrombotic therapy to prevent thromboembolism in atrial fibrillation (AF) and atrial flutter (AFl)
Class I - There is evidence and/or general agreement that the following approaches to antithrombotic therapy are effective in patients with AF or AFl
General principles
1. All patients should be treated except for those with lone AF or contraindications to antithrombotic therapy. 2. The choice of drug should be based upon the absolute risks of thromboembolism and bleeding and the relative risk and benefit for the patient. 3. Among patients treated with warfarin or other oral vitamin K antagonist, the INR should be measured at least once per week at the initiation of therapy and monthly when the degree of anticoagulation is stable.
Anticoagulation with w arfarin or other vitamin K antagonist unless contraindicated:

1. Mechanical heart valves in patients at high risk for thromboembolism* - goal INR 2.0 to 3.0. 2. Mechanical heart valves in patients with atrial fibrillation - goal INR 2.5 or greater based upon the type of valve. 3. More than one validated moderate risk factor# for thromboembolism - goal INR 2.0 to 3.0.
Aspirin (81 to 325 mg/day) is an alternative to vitamin K antagonists in patients at low risk or contraindications to oral anticoagulants.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following approaches to antithrombotic therapy in patients with AF or AFl
The choice of antithrombotic therapy is based upon the same criteria in paroxysmal, persistent, and permanent AF. The need for anticoagulation can be reevaluated at regular intervals. Either aspirin or oral anticoagulation based upon estimation of bleeding risk and ability to safely sustain dose-adjusted oral anticoagulation, and patient preference.
1. Nonvalvular AF or AFl with only one validated moderate risk factor#. 2. Nonvalvular AF or AFl who have at least 2 less well validated risk factors.
In patients without mechanical prosthetic heart valves who are treated w ith oral coagulation, interruption of therapy for up to one w eek without heparin substitution for surgical or diagnostic procedures that are associated w ith a risk of bleeding.
Class IIb - The weight of evidence or opinion is less well established for the usefulness of the following approaches to antithrombotic therapy in patients with AF or AFl
A low er INR goal of 2.0 (range 1.6 to 2.5) in patients 75 years of age who are at increased risk of bleeding but have no contraindication to oral anticoagulation, and in other patients w ith moderate risk factors for thromboembolism*. Among patients at high risk w ho undergo a surgical procedure that requires interruption of oral anticoagulation for more than one w eek, unfractionated heparin or subcutaneous low molecular weight heparin even though the efficacy of these drugs in such patients is uncertain. Follow ing percutaneous coronary intervention or coronary artery bypass graft surgery, low dose aspirin (<100 mg/day) and/or clopidogrel (75 mg/day) may be given w ith oral anticoagulation, but this approach has not been thoroughly evaluated and the risk of bleeding is increased. Among patients undergoing percutaneous coronary intervention, anticoagulation may be temporarily interrupted to prevent bleeding at the peripheral arterial puncture site but should be restarted as soon as possible after the procedure. The maintenance regimen should consist of warfarin plus, to prevent stent thrombosis, clopidogrel (75 mg/day) for a duration that varies w ith the type of stent. When w arfarin is given w ith clopidogrel or
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28/05/2011 Overview of the evaluation and manag aspirin, the dose intensity must be carefully regulated.
Among patients 60 years of age with heart disease or other risk factors for thromboembolism, the thromboembolism risk is low w ithout antithrombotic therapy and the efficacy of aspirin for primary prevention of thromboembolism in relation to the risk of bleeding has not been established. Among patients w ho have an ischemic stroke or systemic embolic event despite warfarin or other vitamin K antagonist at an INR of 2.0 to 3.0, increasing the goal INR to a maximum goal of 3.0 to 3.5 rather than adding an antiplatelet drug.
Class III - There is evidence and/or general agreement that the following approaches are not useful or may be harmful in patients with AF or AFl
Long-term therapy with w arfarin or other vitamin K antagonist for the primary prevention of thromboembolism in patients under age 60 years w ho do not have heart disease (lone AF) or any risk factors for thromboembolism*# * Highest risk factors are prior thromboembolism and rheumatic mitral stenosis. # Validated moderate risk factors for thromboembolism; age 75 years, especially women, hypertension, left ventricular ejection fraction 35 percent or fractional shortening <25 percent, heart failure, and diabetes mellitus. Less w ell validated risk factors for thromboembolism: age 65 to 74 years, w omen, and coronary artery disease. Data from Fuster, V, Ryden, LE, Cannom, DS, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006; 48:e149.
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Number of patients with nonrheumatic atrial fibrillation who need to be treated to prevent one stroke
Number needed to treat to prevent one stroke in two years*
Aspirin: 227 (132 to 2500)
Annual stroke risk
Clinical features
Low (about 1 percent)
Age <65, no major risk factors (including prior stroke, systemic embolism, or transient ischemic attack; hypertension; and poor left ventricular function as determined by a clinical history of heart failure or left ventricular ejection fraction <50 percent) Age 65 to 75, no major risk factors
Low moderate (about 1.5 percent) High moderate (about 2.5 percent) High (about 6 percent) Very high (about 10 percent)
Aspirin: 152 (88 to 1667) W arfarin: 54 (46 to 69)
Age 65 to 75, no major risk factors but either diabetes mellitus or coronary heart disease
W arfarin: 32 (28 to 42)
Age <75 with hypertension, left ventricular dysfunction, or both; or age >75 w ithout other risk factors Age >75 with hypertension, left ventricular dysfunction, or both; or any age and prior stroke, transient ischemic attack, or systemic embolism
W arfarin: 14 (12 to 17) W arfarin: 8 (7 to 10)
* Drugs listed are those recommended by 2001 ACCP Consensus Conference in patients w ithout contraindcations to the suggested therapy; w ith warfarin, the taget INR is 2.0 to 3.0). Adapted from Straus, SE, Majumdar, SR, McAlister, FA, JAMA 2002; 288:1388.
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Warfarin prevents stroke in atrial fibrillation
The incidence of stroke (in percent of patients affected per year) in patients with atrial fibrillation according to age and the presence or absence of risk factors (RF) for stroke. The latter include increasing age, hypertension, heart failure, a prior embolic agent, and diabetes mellitus. The results represent pooled data from five randomized controlled trials. Patients treated with warfarin (red columns) had a marked reduction (average 68 percent) in the incdience of stroke in all age groups compared to those treated with placebo (blue columns). The one exception was patients under the age of 65 who had no other risk factors (lone atrial fibrillation). These patients did not benefit from warfarin and had the lowest risk of stroke (one percent per year). Data
from: Atrial Fibrillation Investigators, Arch Intern Med 1994; 154:1449.
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Atrial fibrillation increases mortality in men and women
Among 5209 subjects in the Framingham Heart Study, the mortality after a 10 year follow-up was higher in both men and women, aged 55 to 74, who had atrial fibrillation (AF) compared to those without AF (p<0.001) A similar relationship was seen in subjects between the ages of 75 and 94 (not shown). Data from Benjamin, EJ, Wolf, PA, D'Agostino, RB, et al,
Circulation 1998; 98:946.
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Overview of the evaluation and manag

Offic ial reprint from UpToDate www.uptodate.c om 2011 UpToDate

Overview of the evaluation and management of atrial fibrillation

Last literature review version 19.1: enero 2011 |

This topic last updated: enero 8, 2010

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Encainide and flecainide increase cardiac mortality

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

ACC/AHA/ESC guideline summary: Pharmacologic cardioversion of atrial fibrillation (AF)

Overview of the evaluation and manag

Potential adverse effects

Intravenous Oral Intravenous

QT prolongation, torsade de pointes, gastrointestinal upset, hypotension

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

Odds ratio versus control (95% CI, number of trials)

Sustained ventricular arrhythmia in trials reporting side effects, percent

Overview of the evaluation and manag

Guidelines for the control of rate and rhythm in atrial fibrillation/flutter-I

Impaired cardiac function EF <40 percent or HF

Duration <48 hours

Duration >48 hours or unknown

Overview of the evaluation and manag

Guidelines for the control of rate and rhythm in atrial fibrillation/flutterII

Overview of the evaluation and manag

ACC/AHA/ESC guideline summary: Maintenance of sinus rhythm in atrial fibrillation (AF)

Overview of the evaluation and manag

Potential adverse effects

Disopyramide Dofetilide Flecainide

Overview of the evaluation and manag

Abnormalities of conduction or impulse formation

Overview of the evaluation and manag

The rate of recurrent atrial fibrillation is lowest with amiodarone

Overview of the evaluation and manag

Amiodarone for maintenance of sinus rhythm in SAFET

Overview of the evaluation and manag

Amiodarone and sotalol in ischemic heart disease in SAFE-T

Overview of the evaluation and manag

Management algorithm of permanent atrial fibrillation - rate control

Overview of the evaluation and manag

Overview of the evaluation and manag

Overview of the evaluation and manag

2.5 to 5 mg IV bolus over 2 min; up to 3 doses 0.15 mg/kg

0.25 mg/kg IV over 2 min 0.075 to 0.15 mg/kg over 2 min

Overview of the evaluation and manag

Rate control versus rhythm control in AFFIRM