Antiarrhythmic Drugs for Atrial Fibrillation

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There are two general approaches to treating atrial fibrillation: 1) attempt to get rid of the atrial fibrillation altogether, and restore and maintain a normal heart rhythm (the rhythm control approach); and 2) allow the atrial fibrillation to persist, while controlling the heart rate (the rate control approach).

    Given these two options, without knowing anything more, almost anyone would start out preferring the rhythm control approach. However, in actual practice this approach often turns out to be less effective and less safe than the rate control approach.

    The reason the rhythm control strategy is often a problem is that antiarrhythmic drugs are usually necessary for restoring and maintaining a normal heart rhythm. These drugs tend to be relatively ineffective, relatively toxic, or both.

    (Note that in some patients, getting rid of the atrial fibrillation with an ablation procedure is feasible.)

    The thing that is especially concerning about antiarrhythmic drugs is their unique toxicity, which often makes them difficult and relatively risky to administer and to take.

    Toxicity of Antiarrhythmic Drugs

    There are two general kinds of toxicity commonly seen with antiarrhythmic drugs falls into two general categories: the usual kinds of side effects seen with many drugs (such as allergies, insomnia, gastrointestinal disturbances, etc.), and proarrhythmia.

    It is proarrhythmia that poses the major problem with antiarrhythmic drugs.

    Proarrhythmia

    "Proarrhythmia" simply means causing cardiac arrhythmias.

    That is, instead of eliminating arrhythmias these drugs can actually produce them. Antiarrhythmic drugs work by changing the electrical properties of cardiac tissue.

    It turns out that whenever you change those electrical properties two different things might happen - you might make arrhythmias less likely to occur (which is the aim), or you might instead make arrhythmias more likely to occur.

    Worse, the types of arrhythmias produced with proarrhythmia (in contrast to the atrial fibrillation itself) can be fatal. Therefore, any time antiarrhythmic drugs are used, there is at least some risk of causing life-threatening arrhythmias - which should make doctors and patients reluctant to use them unless they are truly necessary.

    Some drugs are more likely to cause proarrhythmia than others, and some patients are more likely to experience proarrhythmia than others. The likelihood of proarrhythmia with a particular drug in a particular patient must be taken into account before these drugs are prescribed.

    Antiarrhythmic Drugs Used for Atrial Fibrillation

    Six antiarrhythmic drugs are often used to treat atrial fibrillation: propafenone (Rhythmol), flecainide (Tambocor), sotalol (Betapace), dofetilide (Tikosyn), amiodarone (Cordarone), and dronedarone (Multaq).

    For anybody taking these drugs, the treatment must be carefully individualized to minimize the risk of toxicity, but the following generalizations can be made:

    • Rhythmol and Tambocor are relatively well tolerated as long as they do not cause proarrhythmia. In patients who are young and healthy, who have no underlying heart disease and are at very low risk for developing heart disease, they also cause very little proarrhythmia, and in these patients they may be a good choice for trying to restore a normal rhythm in patients with atrial fibrillation. They are considered moderately effective. However, in patients who have any type of underlying heart disease - or who are at increased risk of developing heart disease - these drugs are especially likely to cause life-threatening proarrhythmia, and should always be avoided.
    • Betapace and Tikosyn are also relatively well tolerated as long as they do not cause proarrhythmia. However, these drugs can produce proarrhythmia in anyone, and careful precautions must be taken by doctors to minimize the risk. Indeed, in the case of Tikosyn, the FDA has declared that doctors must take special training before they are allowed to administer this drug. These drugs are moderately effective in controlling atrial fibrillation.
    • Cordarone is a truly unique antiarrhythmic drug. While it is more effective than any other drug in treating atrial fibrillation, and while it causes relatively little proarrhythmia, it is exceedingly likely to cause other side effects that can be quite significant and even life-threatening. As a result, Cordarone ought to be avoided whenever possible. When it is used, careful monitoring must be made for toxicity as long as the patient takes the drug - and for several months after the drug is stopped. You can read about the unique aspects of Cordarone here.
    • Multaq is a cousin of Cordarone, and was developed with the hope it would be as effective as Cordarone without the toxicity. But, while Multaq is indeed far less toxic than Cordarone, it is not as effective in controlling atrial fibrillation. Also, Multaq cannot be used in people who have had heart failure. Here is more information on the use of Multaq in treating atrial fibrillation.

    The Bottom Line

    It should be clear that treating atrial fibrillation with antiarrhythmic drugs - that is, the strategy of trying to restore and maintain a normal rhythm - can be very problematic. For this reason, added to the fact that clinical trials have shown no overall benefit to this treatment strategy, in many patients it is better to avoid antiarrhythmic drugs altogether and opt instead for a rate-control treatment strategy.

    Sources:

    Fogoros, RN. Treatment of Supraventricular Arrhythmias. In: Fogoros, RN. Antiarrhythmic Drugs - A Practical Guide. Blackwell Publishing, Malden, MA: 2007.

    American College of Cardiology Foundation, American Heart Association, European Society of Cardiology, et al. Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 2013; 127:1916.

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