Eleven Things I Know About A-Fib Drug Therapy by Dr. Peter Kowey
Report by Steve S. Ryan, PhD
This is my only report from the November 2014 meeting of the American Heart Association. Unlike the annual (Boston) AF Symposium, the AHA had only a few sessions on Atrial Fibrillation.
About Dr. Peter Kowey: An internationally respected expert in heart rhythm disorders. His research has led to the development of dozens of new drugs and devices for treating a wide range of cardiac diseases. Note: In his disclosure statement, he lists being a consultant for most of the major pharmaceutical companies.
Dr. Kowey’s first point is a sobering statement about today’s antiarrhythmic drugs (AADs).
Fact #1 “An antiarrhythmic drug is a poison administered in a therapeutic concentration.”
(Like most meds, antiarrhythmic drugs, (AAD), are a trade-off. We trade the unnaturalness and possible toxicity of AADs in the hope that they will alleviate our A-Fib symptoms and keep our A-Fib from getting worse. But AADs are unnatural substances not normally found in our body. Our body has a tendency to react to them like they were toxins.)
Fact #2 Amiodarone is by far the most effective of the antiarrhythmics but is also the most toxic.
The “protean toxicity” of amiodarone is grossly underappreciated by practicing doctors. The average GP or cardiologist often doesn’t understand how severely amiodarone can affect people and often don’t monitor patients closely enough.
Amiodarone has never been reviewed or approved by the FDA for the treatment of A-Fib (this is called “off label” use).
Though doctors use the 200 mg dose, the best dosage is unknown. The degree and rate amiodarone is absorbed into the circulation (bioavailability) can range widely from 15% to 85%.
An antiarrhythmic drug is a poison administered in a therapeutic concentration.
Fact #3 We choose antiarrhythmic drugs based on their relative chances of harm, not comparative efficacy.
Doctors usually start out by prescribing the least dangerous antiarrhythmic first or the least likely to have bad side effects in a particular patient, rather than the drug most likely to suppress A-Fib.
Fact #4 Antiarrhythmic drug therapy is highly empiric, but exposure-related.
For example, in practice doctors don’t use plasma monitoring to determine how much of an antiarrhythmic is actually in a patient’s blood.
In clinical practice most doctors don’t continually adjustment dosage based on patient response.
Fact #5 Antiarrhythmics drugs require surveillance of varying intensity.
• Amiodarone requires intense surveillance—lungs, thyroid, eyes, liver, skin, heart. (For more see my article, Amiodarone: Most Effective and Most Toxic.)
• Flecainide/Propafenone: check for ischemic effects (swelling)
• Sotalol/Dofetilide: check for renal function
• Sotalol: monitor kidneys as 100% is renally eliminated
Fact #6 Antiarrhythmic drugs with multi-channel effects may be more effective than those that target single channels or receptors.
Dr. Kowey discussed Vanoxerine which is a dopamine transporter antagonist developed for Parkinson’s and depression but is being studied for A-Fib conversion.
In one study, ‘Pill-In-The-Pocket’ didn’t reduce A-Fib symptoms but did significantly reduce emergency room visits and hospitalizations.
Fact #7 Antiarrhythmic drug therapy of A-Fib is imperfect.
The goal is palliation (treatment without dealing with the underlying cause) and not total eradication of symptoms.
Fact #8 Antiarrhythmic drug therapy can be creative.
Instead of taking an antiarrhythmic drug on a continuous basis, one can instead use a strategy like Pill-In-The-Pocket. The A-Fib patient only takes an antiarrhythmic drug at the time of an A-Fib attack (or as a booster—taking more of an AAD at the time of an A-Fib episode).
In one study, Pill-In-The-Pocket didn’t reduce A-Fib symptoms but did significantly reduce emergency room visits and hospitalizations.
Fact #9 Antiarrhythmic drugs may supplement the efficacy of other interventions like catheter ablation.
After a catheter ablation during the 3 month blanking period, patients are often given an antiarrhythmic drug to help their heart ‘learn’ to beat normally again, to prevent their heart from slipping back into A-Fib.
About the 3 month blanking period, Dr. Kowey says “the rationale for which is unknown.” (But it generally takes that long for the scarring from an ablation to heal and for the heart to return to normalcy.)
There haven’t been any clinical trials to guide the choice of drug and dose during the 3 month blanking period.
The concept of “enhanced efficacy” has not been grounded or tested.
Fact #10 Taking antiarrhythmic drugs does not obviate the need for stroke prevention.
There is an inadequate data to form a firm conclusion regarding withdrawal of anticoagulation after a successful ablation. (For more see the FAQs question #15: “I’ve had a successful Pulmonary Vein Ablation to cure my A-Fib. Do I still need to be on blood thinners like Coumadin or aspirin?”
Some studies indicate that anticoagulants can be stopped 3-6 months after a successful Pulmonary Vein Ablation. As Dr. John Mandrola says, “and if there is no A-Fib, there is no benefit from anticoagulation.”)
Abundant data prove the prevalence of silent A-Fib.
Dr. Kowey stated that there is an unwarranted assumption regarding the relationship between A-Fib appendage function and clot. (But some studies indicate that 90%-95% of A-Fib clots come from the Left Atrial Appendage (LAA), that closing off the LAA does reduce A-Fib stroke risk.)
After a successful Pulmonary Vein Ablation…and if there is no A-Fib, there is no benefit from anticoagulation. -Dr. John Mandrola
Fact #11 The holy grail is prevention.
But there is no proof that any treatment is conclusively effective in this regard. Dr. Kowey discussed the new drug in development ‘LCZ696’ by Novartis AG which shows promise in preventing A-Fib.
Dr. Kowey’s Conclusions
• If doctors made better and more intelligent use of antiarrhythmic drugs, patients would fare better and we would do fewer ablations.
• Intelligent use requires an in-depth knowledge of pharmacology and familiarity with all aspects of clinical use, especially dosing.
• Antiarrhythmic therapy is not perfect, but it can improve quality of life and functionality for a significant percentage of A-Fib patients.
Dr. Kowey’s statement that “an antiarrhythmic drug is a poison administered in a therapeutic concentration” should set off alarm bells for patients. In the US, we’ve been conditioned to think “ if we’re sick, just take a pill”. But today’s antiarrhythmic drugs have poor success rates (often under 50%), often have unacceptable side effects, and when they do work they tend to lose their effectiveness over time. In general, antiarrhythmic drugs are toxic substances which aren’t meant to be in our bodies―so our bodies tend to reject them.
Antiarrhythmic drugs are certainly better than living a life in A-Fib. They are useful for many patients. But as Dr. Kowey states, they are “palliative” (without dealing with the underlying cause) and are seldom a lasting cure for A-Fib.
Last updated: Sunday, February 15, 2015