Pharmacologic Management of Chronic Atrial Fibrillation

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, affecting approximately 2.2 million Americans.¹ The prevalence of AF in the general population is <1%, but the prevalence increases with age, with >6% of patients >80 years of age having the arrhythmia.¹ Compared to patients with normal sinus rhythm, patients with AF are at a higher risk of both thromboembolic stroke and death.¹

AF is a supraventricular tachyarrhythmia characterized by a disruption of organized electrical conduction and coordinated atrial contraction that results in an irregular heart rhythm. Commonly associated with the development of AF, in addition to increasing age, are ischemic heart disease, hypertension, valvular disease, and dilated cardiomyopathy.² Patients with chronic AF often are asymptomatic. Patients may, however, experience such symptoms as palpitations, shortness of breath, chest pain, or syncope. The definitive diagnosis of AF is made using an electrocardiogram.

Several classifications of AF are used, based on how long the patient has had the arrhythmia. AF that is classified as paroxysmal occurs in short recurrent episodes, whereas persistent and permanent AF are chronic in nature. Although this differentiation commonly is made based on duration, paroxysmal AF confers the same thromboembolic risk as persistent or permanent AF. The purpose of this article is to review the treatment strategies used for paroxysmal, persistent, and permanent AF. The overall treatment goals for patients with AF are listed in Table 1.

Rhythm Control

For most patients, restoring normal sinus rhythm is the most desirable outcome. Doing so would maintain a normal ejection fraction, improve hemodynamics, and prevent thromboembolic complications. Patients who are more likely to be converted to normal sinus rhythm are those who have had AF for a short duration. Patients who are not successfully cardioverted should be managed medically, using rate control and anticoagulation.

Cardioversion of AF may be conducted using either direct current or pharmacologic agents. Direct current cardioversion most often is used in patients who are hemodynamically unstable or who previously failed chemical cardioversion. Pharmacologic treatment options for acute cardioversion include amiodarone, ibutilide, dofetilide, flecainide, propafenone, and procainamide.

Antiarrhythmic agents used to maintain normal sinus rhythm include amiodarone, quinidine, procainamide, disopyramide, flecainide, propafenone, sotalol, and dofetilide. Advantages to using antiarrhythmics include a reduction in symptoms such as palpitations and dyspnea, a decreased need for anticoagulants for the prevention of thromboembolic events, and a reduced risk of heart failure.³ Although using antiarrhythmics has many benefits, these agents have serious side effects and must be used with caution. The use of class 1C antiarrhythmics (flecainide, propafenone) has fallen out of favor because of the proarrhythmic effects and increased risk of mortality associated with the agents.⁴ Although it is known to cause pulmonary fibrosis and hypothyroidism, amiodarone is preferred for chronic use in patients with structural heart defects.

Rate Control

Pharmacologic agents used to control the ventricular rate during AF include beta-blockers (eg, metoprolol), nondihydropyridine calcium channel blockers (eg, diltiazem and verapamil), and digoxin. Heart rate is considered to be at goal if it is between 60 and 80 beats per minute while the patient is on rate-controlling agents.³ For optimal ventricular rate control, betablockers and calcium channel blockers often require high doses, which may lead to adverse events not tolerable to patients.³ Digoxin generally is not considered first-line therapy because multiple drug therapy is often necessitated to control heart rate and because digoxin requires therapeutic drug monitoring for toxicity.

Agents used for rate control in AF also are useful in treating disease states such as hypertension and heart failure, and therefore they could be chosen to treat multiple disease states simultaneously. Although these agents are considered to be safer than the antiarrhythmics, bradycardia, hypotension, and the need for anticoagulation for the prevention of thromboembolic events still remain as possible risks.

In some patients with persistent AF, a clinical quandary exists as to whether rhythm control should be attempted via cardioversion or whether those patients could be as effectively managed using rate control and anticoagulation. Therefore, several randomized clinical studies have been conducted to evaluate the efficacy and mortality associated with these 2 treatment strategies.^5-9 A recent meta-analysis of these trials determined that rate control was at least as effective as rhythm control in reducing the occurrence of ischemic stroke and all-cause mortality.¹⁰ These data support the notion that rate control with anticoagulation may be at least therapeutically equivalent to rhythm control for maintenance treatment of many patients with persistent AF.¹⁰

Prevention of Thromboembolic Stroke

AF is an independent risk factor for stroke. On average, the risk of thromboembolic stroke in patients with AF is 5% per year without anticoagulation, which is 5-fold higher than that for the general population.1 In higher-risk individuals?such as those with comorbid disease states, prior stroke, or greater age?the likelihood of stroke may be as high as 10% per year or more.^1,11 It is important to note that the risk of thromboembolic stroke is similar for patients with both paroxysmal and chronic AF. Because thromboembolic stroke has the potential to result in substantial morbidity and mortality, anticoagulation is an important component of the management of patients with AF.

Outside of the pericardioversion period, thromboembolism associated with AF is caused by the generation of mural thrombi in static pools of blood in the atria. The 2 classes of agents that are used to prevent this thrombus formation and subsequent embolization are antiplatelet agents (eg, aspirin and clopidogrel) and vitamin K antagonists (eg, warfarin). Drug selection is patient-specific and is dependent on a given patient's risk factors for stroke and hemorrhage (Table 2). According to clinical practice guidelines, patients at the highest risk of stroke should receive warfarin therapy with a target international normalized ratio range of 2.0 to 3.0.12 For patients at the lowest risk, the risk of bleeding with warfarin may not outweigh the risk of stroke, so aspirin therapy (325 mg po daily) is recommended.¹² Patients who have contraindications or are at high risk for falls may not be appropriate candidates for warfarin therapy.

A new class of anticoagulants, the direct thrombin inhibitors, is currently being investigated in clinical trials. Direct thrombin inhibitors offer the potential advantage of more predictable dosing and therefore less frequent laboratory monitoring than is necessary with warfarin therapy. This new class of agents may be used in the future to prevent thromboembolic stroke in patients with AF.

The Role of the Pharmacist

Because patients have regular access to pharmacists when they pick up prescriptions, pharmacists are in a prime position to provide both medication and disease state counseling and therefore to add to the care of a patient with AF. Pharmacists should educate patients regarding optimal medication administration and storage, potential adverse events, and in what circumstances to seek immediate medical care. Furthermore, pharmacists must be familiar with the recommendations of the most current clinical practice guidelines to advise health care practitioners concerning drug selection, monitoring, and management.

Conclusion

AF is a very common arrhythmia that requires several modalities of treatment to accomplish a variety of therapeutic goals. Pharmacists play an important role in the care of patients with AF as the primary medication experts on the medical team. They can provide information to other health care providers and to patients regarding optimal medication management.

Drs. Hajjar and Reese are assistant professors of clinical pharmacy at the University of the Sciences in Philadelphia, Philadelphia College of Pharmacy.

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