Pharmacological management of AF

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Robert J DiDomenico
PharmD
Clinical Assistant Professor
Colleges of Pharmacy (Department of Pharmacy Practice) and Medicine (Section of Cardiology)
University of Illinois at Chicago
USA
E:[email protected]

Atrial fibrillation (AF) is the most common cardiac dysrhythmia that occurs in adults. It is a disease of the elderly, occurring in as many as 8% of adults aged 80 years or older, compared with <1% in patients younger than 60 years of age.(1,2) Over the last two decades, the number of hospitalisations for AF have increased two- to threefold, contributing to over two million hospital admissions annually.(3) For patients hospitalised with AF, the length of stay ranges from 1–7 days in more than 70% of patients.(3) The cost of treating AF has been estimated at more than €3,200, more than half of which was directly attributable to hospitalisation costs.(4)

The presence of AF increases a patient’s risk for adverse cardiac events. The risk of ischaemic stroke in patients with nonvalvular AF is approximately 5% annually, and mortality risk is between 1–2% per year.(5–7) Because hypertension, ischaemic heart disease and heart failure are comorbidities common to patients with AF, the development of AF may also exacerbate these underlying conditions, increasing morbidity in these patients. Therefore, when the morbidity associated with AF is coupled with rising hospitalisation rates and significant economic burden on the healthcare system, effective treatment strategies are needed to minimise adverse cardiac events and prevent hospitalisations.

Treatment
The treatment goals for AF are twofold:

• Reduce or alleviate symptoms.
• Prevent complications.

Rate control
For patients with AF and a rapid ventricular response, symptom relief can usually be achieved by reducing heart rate (rate control). For patients with AF, the goal is to maintain a resting heart rate between 60–80bpm and an exercise heart rate of 90–115bpm.(8) Beta-blockers, nondihydropyridine calcium channel blockers and digoxin are all effective in controlling heart rate in patients with AF and are often used in combination with one another. When a rapid response is desired, these drugs may be administered intravenously. In the absence of hypotension, acute heart failure symptoms or evidence of conduction through an accessory pathway, beta-blockers or calcium channel blockers are generally preferred as initial therapy (see Figure 1).(8) In patients with either hypotension or evidence of acute heart failure, digoxin may be preferred (in the absence of renal failure). Alternatively, intravenous amiodarone may be considered in critically ill patients in need of rate control. In patients with refractory ­tachycardia or those who have persistent symptoms despite adequate rate control, rhythm control may be necessary (see below).

[[HPE26_fig1_31]]

Anticoagulation
Once adequate rate control has been achieved, an assessment of stroke risk must be made and appropriate anticoagulation initiated. The CHADS2 index is a relatively simple and accurate tool to assess stroke risk in patients with AF and subsequently determine appropriate anticoagulation.(9) Patients with AF are assessed for the presence of the ­following characteristics:

• C: history of congestive heart failure.
• H: history of hypertension.
• A: age >75 years.
• D: history of diabetes mellitus.
• S(2): history of stroke or transient ischaemic attack (TIA).

Each characteristic is assigned 1 point, except for history of stroke or TIA, which is assigned 2 points. The points are added together to yield the CHADS(2) score (range 0–6) to estimate stroke risk. A CHADS(2) score of 0–1 is deemed low risk, 2–3 is considered moderate risk and ≥4 is considered high risk.

Anticoagulation therapy should be tailored to an individual patient’s estimated risk of stroke. Using the CHADS(2) score as an example, in the absence of contraindications, warfarin is indicated in patients with a CHADS(2) score of ≥2 (moderate to high risk) (see Figure 1).(10) However, for patients with a CHADS(2) score <2 or in those with contraindications to warfarin, aspirin therapy is indicated.

Rhythm control
Historically, restoration and maintenance of normal sinus rhythm (rhythm control) was thought to relieve symptoms of AF more effectively, decrease the risk of thromboembolic events, decrease the need for anticoagulation and bleeding risk and, perhaps, decrease mortality. However, in recent years, several studies have challenged this notion. In the AFFIRM study, there was no difference in mortality (primary endpoint) between the rate and rhythm control groups at five years, nor was there a difference in stroke or major bleeding complications.(11) There was, however, an increased risk of hospitalisation in patients managed with the rhythm control strategy (73.0% vs 80.1%, p<0.001). Three subsequent studies demonstrated similar results.(12–14) Because of these findings, many clinicians reserve rhythm control for patients with refractory symptoms despite adequate rate control, those experiencing heart failure symptoms or fatigue while in AF, those who are poor candidates for oral anticoagulation or simply those who prefer rhythm control (see Figure 1).(10)

When the rhythm control strategy is employed, it is imperative that antiarrhythmic drug selection is individualised to minimise the risk of serious adverse events. Class I antiarrhythmic drugs, particularly class Ic agents, are known to increase the risk of ventricular proarrhythmia and sudden cardiac death, particularly in patients with structural heart disease (eg, left ventricular dysfunction, coronary artery disease).(15–17) In patients with left ventricular dysfunction, coronary artery disease or significant left ventricular hypertrophy, the class III antiarrhythmic drugs amiodarone, dofetilide and sotalol are preferred for restoration and maintenance of sinus rhythm and class Ic drugs should be avoided (see Figure 1).(8) However, in patients with AF but structurally normal hearts (ie, “lone” AF), both class Ic and class III antiarrhythmic agents may be used. Regardless of which antiarrhythmic agent is selected, given the risk of proarrhythmia, initiation of these drugs should be done in the hospital setting and patients should be monitored for the development of proarrhythmia until steady-state plasma concentrations have been reached (approximately three days for most drugs).

Conclusion
Atrial fibrillation is a commonly encountered cardiac rhythm disturbance in hospitalised patients and is associated with significant morbidity, resource consumption and healthcare costs. Treatment of patients with AF should focus on alleviating symptoms and preventing complications (eg, stroke). The safest, most effective treatment strategy appears to be rate control in combination with oral anticoagulation. Rhythm control is an option for those patients with intolerable symptoms, contraindications to oral anticoagulation or those who voice a preference for this approach. A multifaceted treatment strategy is necessary to alleviate symptoms, prevent complications and minimise excessive resource utilisation in patients with AF.

References

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