Atrial Fibrillation is the most common type of arrhythmia among adults that is typically characterized by an elevated ventricular rate as well as irregular heart rhythm. There are mainly two approaches to its management. The first is to attempt to correct the arrhythmia with the goal of achieving normal sinus rhythm. This approach is often referred to as “rhythm control” and in generally requires a cardioconversion, followed by medication and / or ablation therapy depending on symptoms and recurrence of atrial fibrillation.  The other approach is to control the ventricular rate without any intervention to address the arrhythmia. This approach is often known as the “rate control” which is typically managed by medication(s) alone.

Which approach is better?

The AFFIRM trial answered this question in 2002. Published in New England Journal of Medicine, the study aimed to evaluate any difference in the survival outcomes between the two approaches.  The study found that there was no demonstrated survival benefits between the two approaches but patients from the rhythm control group had more serious adverse effects, many of them were related to the anti-arrhythmic medications. As such, the standard of practice has generally favoured the rate control approach in atrial fibrillation.

However, the recent Atrial Fibrillation Guideline published by the Canadian Cardiovascular Society have updated its algorithm in determining which approach is more suitable for patients. While the rate control approach is still the first line of therapy, the guideline is acknowledging that early rhythm control may be warranted in the following special circumstances:

  • Highly symptomatic
  • Multiple recurrences
  • Extreme impairment in QOL
  • Arrhythmia-induced cardiomyopathy

Rhythm vs Rate Control in Atrial Fibrillation

Given there is a renewed interest in rhythm control for atrial fibrillation, at least in some selected individuals, we may be seeing more people being prescribed an anti-arrhythmic, with one of the most common agents as amiodarone.

Considerations when Prescribing Amiodarone.

It always seems that there are so many things you have to remember with amiodarone. From its endless list of side effects, to the long list of investigations to be done at baseline and routinely, along with many many drug interactions listed in every drug reference, it can be overwhelming at times.

This is where I can be a real geek – if you only commit yourself to remembering two fundamental pharmacokinetic facts with amiodarone, you can pretty much infer many of its side effects, monitoring requirements as well as the drug interactions:

  • Amiodarone has very long half life.
    • The long half life means it takes a long time for the drug to achieve a reasonable blood concentration to exert its pharmacological effects. As such, loading doses may be used during the initial treatment to expedite the onset of action, especially in the emergency or critical setting.  This also means that it will take a long time to eliminate the drug completely from the body. We often estimate that it takes 5 half lives for the medication to reach steady state blood concentration, and requires the same amount of time to completely eliminate the drug.
    • As per Lexicomp, the mean half life of oral chronic amiodarone therapy is 40 to 55 days (range: 26-107days). You can do the math to figure out how long it will take to reach steady state blood concentration or to completely eliminate the drug!
  •  Amiodarone has very large volume of distribution.
    • This means amiodarone is not confined to the plasma volume and distributed to many places within the body.  The large volume of distribution also means the drug is lipophilic,  likely eliminated via the liver and not through the kidneys. As such, dosage adjustment is not necessary in renal impairment. However, there are many potential drug interactions via the liver CYPP450 system that one must be cognizant of.
    • One of the most critical and relevant drug interaction is between amiodarone and warfarin, where both have long half lives as well as narrow therapeutic windows. Dr. Eric Christianson recently discussed on his blog post on Med Ed 101 here, few key considerations and advices on how to manage such challenging interaction successfully.
    • Other clinically relevant drug interactions include digoxin, simvastatin as well as many antiarrhythmic drugs and QT prolonging agents such as the quinolones.
  • Amiodarone is responsible for many potential side effects from head to toe.
    • Given amiodarone is distributed to many parts of the body but takes a long time to eliminate, it makes sense that amiodarone can results in many non-cardiac side effects
    • Here is a quick summary of the potential side effects as well as recommended method of diagnosis and management strategies (adapted from Am Fam Physician. 2003 Dec 1;68(11):2189-2197)

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Minor Effects

Amiodarone is one of the most common anti-arrhythmic agents used in a community setting for rhythm control in atrial fibrillation. This drug has many unique pharmacokinetic parameters, which in turn, explain its many potential side effects and monitoring requirements.

 

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