U.S. Pharmacist

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Rate Control in Atrial Fibrillation

Mary Ann E. Zagaria, PharmD , MS , CGP
Senior Care Consultant Pharmacist and
President of MZ Associates, Inc.
Staten Island, NY

2/20/2007

Arrhythmias (i.e., disturbances in cardiac rhythm) are more likely to develop in older individuals and in those with other cardiac disorders.1 While potentially anxiety-provoking, arrhythmias are harmless in the majority of individuals; however, some arrhythmias may result in serious consequences (e.g., motor vehicle accidents, falls, heart failure) and, occasionally, sudden death.1 Certain arrhythmias, particularly atrial fibrillation, may cause a stroke or vascular occlusion in a limb secondary to thromboembolism.1 In fact, atrial fibrillation increases the risk of thromboembolic stroke by four- or fivefold. 2 Atrial fibrillation-related stroke has been reported in 1.5% of patients in their 50s and increases to 23.5% of patients in their 80s.2,3 Atrial fibrillation affects approximately 2.3 million adults in the United States. The incidence of atrial fibrillation doubles with each decade of adult life, affecting almost 10% of individuals older than 80.3

Cardiac conduction commences in the heart's natural pacemaker, the sinoatrial node. The sinoatrial impulse activates the atria and atrioventricular node. The atrioventricular node transmits the impulse across the cardiac septum to the bundle of His in the ventricles. The impulse proceeds through the ventricles via the right and left bundle branches and the Purkinje system. Disturbances in this elecrophysiologic system result in disturbances in cardiac rate and rhythm; they are most frequently caused by reentry problems or disturbances in automaticity.4-6

Atrial Fibrillation
Atrial fibrillation (Table 1) is represented by very rapid and disorganized atrial activity. Patients with atrial fibrillation have a rapid and irregularly irregular pulse.3 The atria do not contract and the many electrical stimuli that bombard the atrioventricular conduction system cause inconsistent impulse transmission and an irregularly irregular ventricular rate.3 The impulses that penetrate the atrioventricular node and activate the ventricle result in a loss of atrial contribution toward cardiac output, which can be especially problematic in patients with heart failure who are quite symptomatic upon presentation of atrial fibrillation. Unlike other supraventricular tachycardias, atrial fibrillation is more likely to be chronic than acute.2 Simplistically stated, atrial fibrillation can "wear out" the heart.

Atrial fibrillation is usually indicative of an organic heart disease; however, the risk of cardiovascular morbidity and mortality is considerably increased in seniors with atrial fibrillation, even if they do not have organic heart disease.2 The most common predisposing disorders for seniors and middle-age individuals are hypertension, hyperthyroidism, coronary artery disease, heart failure, heart valve disorders (mitral or tricuspid), and binge alcohol drinking.2,3 Other less common causes include amyloidosis, chronic obstructive pulmonary disease, pulmonary embolism, atrial septal and other congenital heart defects, myocarditis, and pericarditis.2,3

Symptoms of Atrial Fibrillation
Clinicians report a wide variety of symptoms in patients presenting with atrial fibrillation.7

Often, patients are asymptomatic or may complain only of fatigue or vaguely report "not feeling right." Many experience distressing palpitations or chest discomfort secondary to significant increases in heart rate and irregular rhythm.2,3 Dyspnea, weakness, and light headedness secondary to heart failure are potential consequences of atrial fibrillation. In addition, reduced cognitive function, signs and symptoms of acute sroke, and necrosis or malfunction of a limb or organ (secondary to systemic emboli) may be seen.

Diagnosis of atrial fibrillation is made by electrocardiogram. Classifications of atrial fibrillation are listed in T able 1.

Chronic atrial fibrillation can be well tolerated, particularly if the ventricular response remains less than 100 beats/minute; however, the longer the duration of atrial fibrillation, the less likely spontaneous conversion will occur and the more difficult cardioversion is to attain.2,3 If symptoms are severe and indicative of unstable or complicated atrial fibrillation (e.g., angina, heart failure, acute hypotension, pulmonary edema), direct-current cardioversion is indicated.8   

Treatment Goals and Management
The treatment goals of atrial fibrillation are to (1) control rapid ventricular response; (2) prevent thromboembolic events/complications; (3) restore sinus rhythm; and (4) prevent further recurrences of atrial fibrillation.7 Therefore, once any specific cause of atrial fibrillation has been managed (e.g., with hospitalization for new onset atrial fibrillation or without hospitalization as is often the case with recurrent atrial fibrillation), treatment focuses on ventricular rate control, rhythm control, and prevention of thromboembolism.3

Results from five randomized trials indicate that controlling ventricular rate in patients with atrial fibrillation is at least as effective as controlling rhythm with respect to several specific outcomes; the necessity of continuing antithrombotic treatment was noted, even when long-term sinus rhythm is obtained.9

According to the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) 2006 Guidelines for the Management of Patients with Atrial Fibrillation, "medications and ablation are effective for both rate and rhythm control, and in special circumstances surgery may be the preferred option." 8 Regardless of the approach, the guidelines also recommend the need for anticoagulation "based on stroke risk and not on whether sinus rhythm is maintained."8 It is important to note that clinical judgment is crucial in selecting the appropriate treatment strategy since patients can present with a wide variety of symptoms.7 Ultimately, patient characteristics and severity of symptoms guide the selection of methods aimed at attaining these goals.9

Initially, the goal of therapy in the elderly, as in younger patients, is to slow ventricular rate using IV agents.2 As mentioned earlier, direct-current cardioversion may be required to immediately restore sinus rhythm in those patients with severe or intolerable symptoms.7

Ventricular rate control: Tachycardia-induced atrial remodeling occur in patients who have poor control of ventricular rate and chronic tachycardias can result in a progressive decline in left ventricular function.7 Therefore, it is important to address ventricular rate control early in the course of atrial fibrillation. To control symptoms and prevent tachycardia-induced cardiomyopathy, patients with atrial fibrillation require ventricular rate control aimed at less than 80 beats/minute at rest.3 The ACC/AHA/ESC guidelines state that depending on symptoms, "rate control may be reasonable initial therapy in older patients with persistent atrial fibrillation who have hypertension or heart disease."8 For younger patients, especially those with paroxysmal lone atrial fibrillation, rhythm control may be a better initial choice of therapy.8

An acute onset of symptoms, including rapid ventricular rate (e.g., 140 to 160 beats/minute), requires treatment with intravenous agents (beta-blockers, digitalis, adenosine, lidocaine, nondihydropyridine calcium channel blockers). These agents block the atrioventricular node by slowing conduction and increasing refractoriness. 3 Beta-blockers (e.g., metoprolol, esmolol) are selected as first-line treatment if excess catecholamines, such as exercised-induced atrial fibrillation or thyrotoxicosis, are suspected.3,7 While these patients are highly responsive to the beta-blockers, they are often resistant to digoxin.7 Nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazem) are also effective and provide a rapid decrease in ventricular rate and symptomatic relief. Digoxin is slow in onset, the least effective, and may be utilized in patients with heart failure.3,7,8 For long-term ventricular rate control, oral administration of beta-blockers, nondihydropyridine calcium channel blockers, and digoxin may be used.3

The caveat associated with the use of digoxin in the elderly is that decreased renal clearance in this population may lead to increased risk of toxic effects.10 Amiodarone may be required in patients who do not respond to individual or combined beta-blockers, nondihydropyridine calcium channel blockers, or digoxin;3 however, in the elderly, amiodarone is considered to be potentially inappropriate, as its use is associated with QT interval problems and risk of provoking torsade de pointes.10,11

It should be noted that although Wolff-Parkinson-White syndrome is rare in the elderly, intravenous beta blockers, digoxin, lidocaine, adenosine, and nondihydropyridine calcium channel antagonists are contraindicated in patients with this condition, since use of these agents may result in acceleration of ventricular rate, hypotension, or ventricular fibrillation.2,8 In patients with this condition, early direct-current cardioversion can be used in hemodynamically compromised patients, while class I antiarrhythmic agents or amiodarone may be administered intravenously in hemodynamically stable patients.8 Oral administration of beta-blockers and calcium channel blockers are acceptable for long-term use.8 When a patient cannot tolerate or does not respond to a rate-controlling medication, radiofrequency ablation of the atrioventricular node may be performed resulting in complete heart block and the need for permanent pacemaker insertion.7

Rhythm control: The ACC/AHA/ESC practice guidelines provide a comprehensive review of the pharmacologic and nonpharmacologic therapeutic options for rhythm control.8 Pharmacotherapy is typically considered first-line treatment, while left atrial ablation is considered second-line therapy.   

According to the Cardiac Arrythmia Suppression Trial and other studies, patients being treated for ventricular arrhythmias who have coexisting poor left ventricular function and ischemic heart disease are at increased risk of proarrhythmia.7,12 Since many patients with atrial fibrillation fall into this category, it is important to note that the antiarrhythmic agents that are capable of converting atrial fibrillation to NSR (class Ia, Ic, and III) not only carry the risk of increased adverse events but also might increase mortality.3 Furthermore, if these agents are used in the elderly, decreased renal clearance or hepatic metabolism may place patients at particular risk for toxicity.10 Radiofrequency ablation may be preferred in especially symptomatic, young individuals with atrial fibrillation who require sinus rhythm control, in an attempt to avoid years of medication therapy.8

Prevention of thromboembolism: The current literature, as well as the ACC/AHA/ESC guidelines, indicates that patients at high risk for stroke may require anticoagulation regardless of whether the rate-control or rhythm-control strategy is utilized. Further study is necessary to address this question.8

The prevention of thromboembolism (e.g., warfarin titrated to an international normalized ratio [INR] of 2 to 3) is necessary when cardioversion is employed and as part of the long-term management of most atrial fibrillation patients.3 In patients with recurrent paroxysmal, persistent, or permanent atrial fibrillation in the presence of risk factors for thromboembolism, anticoagulant therapy should be continued indefinitely.3 In healthy patients with a single episode of lone atrial fibrillation, anticoagulant therapy is limited to a four-week course.

In the elderly, warfarin has been shown to reduce stroke risk by 68% in those with non-rheumatic atrial fibrillation, with virtually no increase in significant bleeding.2 In contrast, aspirin has shown only modest protection against stroke in patients with atrial fibrillation.8 While less effective than warfarin, aspirin is utilized in individuals with no risk factors for thromboembolism or in patients for whom warfarin is contraindicated.3,10 Since anticoagulant therapy poses a higher risk of major bleeding in the elderly than in younger patients, the use of anticoagulants should be carefully weighed using a risk-benefit ratio on a case-by-case basis.2 Factors such as risk of falls, adherence to medication and diet, and comorbid conditions should be considered. In addition, the need for continued anticoagulant therapy should be reassessed periodically in all patients with atrial fibrillation.2,8 Warfarin is contraindicated in patients with unsupervised dementia or psychosis.10

The direct thrombin inhibitor ximelagatran does not require INR monitoring and may in fact be equivalent to warfarin; however, further research is necessary before ximelagatran can be recommended in place of warfarin.3 Surgical ligation or closure of the left atrial appendage, the site of over 95% of detected thrombi, may be considered in patients for whom warfarin and antiplatelet therapy are absolutely contraindicated.3,8

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Antagonists (ARBs): ACE inhibitors and ARBs may reduce the incidence of atrial fibrillation as demonstrated in both experimental and clinical trials.8

In patients with atrial fibrillation, ACE inhibitors have been shown to reduce the frequency of atrial premature beats, decrease atrial pressure, and reduce fibrosis (e.g., by possibly lowering the relapse rate after cardioversion).8 Additional information on ACE inhibitors and ARBs can be found in the ACC/AHA/ESC practice guidelines. 8

HMG CoA-Reductase Inhibitors (Statins): Evidence suggests that statin-type cholesterol-lowering agents are effective in maintaining sinus rhythm in patients with persistent lone atrial fibrillation.8 Additionally, theses agents decrease the risk of recurrent atrial fibrillation after successful direct-current cardioversion. 8

Information for Patients and Caregiver
Patients and their caregivers should be aware of lifestyle issues that may impact their condition. This may include raising awareness that during time of illness, the resting heart rate may be elevated.6 Patients should be advised that stress, lack of sleep, and the ingestion of caffeine, chocolate, and alcohol can increase the heart's vulnerability to electophysiologic induction of atrial fibrillation.3,6 In addition, smoking cessation should be encouraged, and if arrhythmias occur during exercise, speaking to a doctor about special precautions to take during exercise is recommended.1,6

Summary
Atrial fibrillation is one of the most common types of arrhrythmias. Its prevalence increases with age and tends to occur in individuals with a cardiac disorder. The risk of cardiovascular morbidity and mortality is considerably increased in seniors with atrial fibrillation, even if they do not have organic heart disease. The longer the duration of atrial fibrillation, the less likely spontaneous conversion will occur and the more difficult cardioversion is to attain. Chronic tachycardias can potentially result in a progressive decline in left ventricular function. Effective ventricular rate control benefits patients by reducing the risk of tachycardia-induced atrial remodeling in patients who have poor rate control. The treatment of atrial fibrillation focuses on ventricular rate control with medications, prevention of thromboembolism with anticoagulant therapy, and if necessary, conversion to normal sinus rhythm using medications or procedural cardioversion. Medications and ablation are effective for both rate and rhythm control.

References
1. Beers MH, Jones TV, Berkwits M, et al; eds. The Merck Manual of Health & Aging. Whitehouse Station, NJ : Merck Research Laboratories; 2004:607, 618-19, 628-631, 638-640, 646, 660.
2. Beers MH, Berkow R, eds. The Merck Manual of Geriatrics. 3rd ed. Whitehouse Station, NJ :Merck & Co.; 2000:617-618, 649-650, 696, 886, 890-892, 897.
3. Beers MH, Porter RS, Jones TV, et al. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ : Merck Research Laboratories; 2006:673-699.
4. Dunphy L, Winland-Brown J. Primary Care: The Art and Science of Advanced Practice Nursing. Philadelphia : F.A. Davis. 2000.
5. Goldman L, Bennett JC. Cecil Textbook of Medicine. Philadelphia : W.B. Saunders Co. 2000. 
6. McCaffrey R, Crouch M, Thrush S. Cardiovascular Disorders. In: Youngkin EQ, Sawin KJ, Kissinger JF, et al. Pharmacotherapeutics: A Primary Care Guide . Upper Saddle River, NJ : Pearson Prentice Hall; 2005:301-347.
7. Bauman JL, Schoen MD. Arrhythmias. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York : McGraw-Hill; 2002:273-303.
8. 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). Available at: www.acc.org/qualityandscience/clinical/guidelines/atrial_fib/pdfs/AF_Full_Text.pdf. Accessed January 8, 2007.
9. Crijns HJ. Rate versus rhythm control in patients with atrial fibrillation: what the trials really say. Drugs. 2005;65(12):1651-67.
10. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 10th ed. Cleveland : Lexi-Comp, Inc.;2005.
11. Fick DM, Cooper JW, Wade WE, et al. "Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults: Results of a U.S. Consensus Panel of Experts. Arch Intern Med. 2003;163(22):2716-2724.
12. Echt DS, Liebson PR, Mitchell E. et al. Mortality and morbidity in patients receiving encainide, flecanide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324:781-788.

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