Pharmacological Approach for AF Management: Interview With Stephen L. Winters, MD, Director, Cardiac Rhythm Management Program

What are the current pharmacological options available for AF patients?

The current pharmacological options available to treat patients with AF are often directed at antithrombotic therapy and efforts to optimally control the ventricular response. With particular reference to individuals who would benefit from drugs designed to suppress the arrhythmia, the selection of a drug typically hinges on which agent the patient will be best able to tolerate. Underlying conditions such as left ventricular hypertrophy, poor ventricular systolic function, and congestive heart failure, as well as numerous noncardiac conditions, often limit which antiarrhythmic drugs can be used.

Approximately how many AF patients do you see in your lab per month? What percentage are treated with antiarrhythmic medication? Do you generally try to treat patients first with medicine before procedures such as ablation are performed?

In our hospital-based cardiac rhythm management program, we typically see at least 60 patients with atrial fibrillation per month. Most of these individuals are seen in the outpatient setting. A fair number have implanted pacemakers or cardioverter-defibrillators. Barring any limiting non-cardiac risk factors, we typically use sotalol or amiodarone in patients with structural heart disease. If the patient has had congestive heart failure due to impaired left ventricular (LV) systolic function, we typically employ amiodarone after obtaining verbal informed consent from the individual. In the absence of structural heart disease or other specific contraindications, we find that therapy with a class 1c antiarrhythmic drug is our first drug of choice. In select situations we will use dofetilide, as well as quinidine or disopyramide, after attempting therapy with other agents.

What are some of the benefits in using Rythmol SR?

Until recently, we had shied away from using propafenone, since it required dosing three times a day. However, with the recent release of Rythmol SR, we have increasingly been prescribing this agent as a first-line therapy in individuals without significant LVH or structural heart disease, in view of its therapeutic benefits and excellent patient acceptance.

What has been your experience with Rythmol SR in your patients?

Thus far, we have been extremely pleased with the benefit that Rythmol SR has provided to our patients. We have been somewhat impressed with our own anecdotal situations in which some patients, who were very troubled with paroxysmal atrial fibrillation and who did not respond well to other twice-daily antiarrhythmic drugs, performed well on Rythmol SR. The ability to start therapy as an outpatient adds to patient comfort and acceptance of use of this drug.

Why is it important to have pharmacological options available for AF patients?

Despite advances in catheter-based and surgical approaches to treat atrial fibrillation, the vast majority of patients who require attempts at suppression of this dysrhythmia are either not candidates for such procedures or are unwilling to undergo them in view of the concern of potential complications and only moderate success rates. Thus, drug suppression remains the most viable option to treat individuals in need of maintenance of sinus rhythm.

How will Rythmol SR impact the management of AF overall?

At least for the foreseeable future, Rythmol SR will help substantially in the management of select individuals with non-permanent forms of atrial fibrillation. The drug is well tolerated and has a relatively low-risk profile with respect to non-cardiac side effects.

Are there any types of patients that Rythmol SR might not work on?

Rythmol SR would not be an appropriate drug to use in patients with significant LVH or structural heart disease. The drug should be avoided in patients with chronic obstructive lung disease, in view of its weak beta-blocking properties. An adjustment in the dose of warfarin may be necessary in patients started on this agent. In situations where atrial fibrillation may be due to transient remedial situations (e.g. hyperthyroidism), Rythmol SR would not be expected to be of substantial benefit.

Describe the difference between rate control and rhythm control.

When drug treatment of atrial fibrillation is raised, one must be more specific of the intended goals. Most patients can be treated adequately with control of the ventricular rate alone using standard drugs (e.g. beta blockers, verapamil, diltiazem, digitalis). Occasionally, patients may require permanent pacing due to excessively slow ventricular responses or lengthy pauses. However, there are increasing efforts to avoid permanent pacing to avoid secondary embarrassment to chronic ventricular function which could develop. Where reasonable, to attempt suppression to avoid permanent pacing, as well as in situations where lack of patient toleration or adverse hemodynamic consequences dictate, efforts to suppress atrial fibrillation with antiarrhythmic drugs are appropriate.

How will trial findings from such studies as RAFT, ERAFT and AFFIRM affect clinical practice?

Studies such as RAFT and ERAFT confirm the potential benefit and high safety margin of Rythmol SR in the suppression of atrial fibrillation in select patients with various forms of atrial fibrillation. Other trials of class 1c antiarrhythmic drugs for similar endpoints recruited relatively very few patients; thus, the data on Rythmol SR is very significant. Whether the results of RAFT and ERAFT can be generalized to treatment with other forms of propafenone or flecainide are unknown, especially since these drugs are now generic and the formulations may vary considerably from those used in the original and relatively small-scaled clinical trials. In patients at risk for thromboembolic complications of atrial fibrillation, treatment with warfarin should be continued even if sinus rhythm is restored and maintained with agents such as Rythmol SR, as suggested from results of the AFFIRM trial. In this landmark study, the stroke risk was found to be unacceptably high in patients who were felt to have adequate suppression of atrial fibrillation with an antiarrhythmic drug when anticoagulation therapy was discontinued. Results of the ongoing ACTIVE trial, contrasting aspirin and Plavix to standard anticoagulation in patients with atrial fibrillation at increased risk of thromboembolic and vascular events, as well as final evaluation of the trials involving use of the thrombin inhibitor, Ximelagatran, are eagerly awaited to see what alternatives to warfarin may be possible in such patients.

How important of a role will pharmacology play AF management in the future?

Until effective and safe curative approaches to managing atrial fibrillation become widely available, efforts to suppress atrial fibrillation with antiarrhythmic drug therapy will remain as a mainstay of therapy. As with catheter-based approaches, further efforts to selectively modulate autonomic inputs to the heart may greatly impact our ability to suppress this disruptive, economically burdensome rhythm disturbance of epidemic proportion. Sponsored by Reliant Pharmaceuticals.