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Antiarrhythmic drug therapy

Video: Stroke Prevention in A-Fib and Anticoagulant Therapy

Through interviews and animations explains how atrial fibrillation can cause stroke and why anticoagulation is so important. Discussion of warfarin (brand name Coumadin), the required (weekly or monthly) monitoring, interactions with food, alcohol and other drugs and the newer anticoagulants (NOACs).

Developed in association with Boehringer Ingelheim [one manufacturer of the new NOACs]. (5:36)

YouTube video playback controls: When watching this video, you have several playback options. The following controls are located in the lower right portion of the frame: Turn on closed captions, Settings (speed/quality), Watch on YouTube website, and Enlarge video to full frame. Click an icon to select.

If you find any errors on this page, email us. Y Last updated: Monday, January 15, 2018

Return to Instructional A-Fib Videos and Animations

Eleven Things I Know About A-Fib Drug Therapy by Dr. Peter Kowey

Peter R. Kowey MD 2.150 pix at 96 res

Dr. Peter R. Kowey

Dr. Peter Kowey, American Heart Association (AHA) Scientific Sessions, November 17, 2014, Chicago, IL

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.

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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.

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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.

Editors Comments:
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.
Reference for this Article
Alboni, P. et al. Outpatient Treatment of Recent-Onset Atrial Fibrillation with the “Pill-in-the-Pocket” Approach. N Engl J Med 2004; 351:2384-2391 Last accessed Jan 25, 2015. URL:

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Last updated: Sunday, February 15, 2015

Catheter Ablation as Recommended First Choice – 2014 Boston AF Symposium

Dr. Hugh Calkins, Johns Hopkins Medical Center

Dr. Hugh Calkins

2014 Boston AF Symposium

Catheter Ablation as Recommended First Choice

Report by Dr. Steve S. Ryan, PhD, August 26, 2014

Dr. Hugh Calkins from Johns Hopkins gave a presentation entitled “Indications for AF Ablation: Guidelines vs. Clinical Reality.”

To begin his presentation, Dr. Calkins asked the Symposium attendees:

“Which statement correctly reflects your current approach to AF ablation as first line therapy in patients with symptomatic paroxysmal AF?”

•  I rarely recommend AF ablation as first line therapy in this patient group.

•  I routinely recommend AF ablation as first line therapy in this patient group.

Response: 79% of the attendees selected choice #1 {They used an electronic polling system placed at each seat.]


According to the 2012 Guidelines (ESC Focused Update)1:

“Symptomatic AF refractory or intolerant to at least one Class 2 or 3 antiarrhythmic medication, catheter ablation is recommended.” With the following footnote: “Catheter ablation of symptomatic AF is considered a Class 1 indication only when performed by an electrophysiologist who has received appropriate training and is performing the procedure in an experienced center.”

“Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a class 2 or 3 antiarrhythmic, Catheter ablation is reasonable.”

[If a paroxysmal patient has no or minimal structural heart disease, their first line choice can be catheter ablation or the antiarrhythmic meds dronedarone, flecainide, propafenone, or sotalol. Should these antiarrhythmics fail, the patient can choose catheter ablation or amiodarone.]

Dr. Calkins also asked “And What About Ablation in Patients with Asymptomatic AF?”

He notes that the indications listed in all guidelines refer only to patients with symptomatic atrial fibrillation. No mention is made of asymptomatic AF. In rare circumstances, it may be reasonable to perform AF ablation in a truly asymptomatic patient with the aim of reducing long term consequences of AF including increased risk of stroke, heart failure, and dementia.

But patients need to be aware of the immediate risks of AF ablation and also that AF ablation has not been shown to reduce the risks of stroke, heart failure, or dementia. [But see my article Live Longer—Have a Catheter Ablation’. In this research (published after Dr. Calkins’ presentation) they found that a successful PVI reduces by 60% the risk of death from stroke and other cardiovascular events. Though some consider this study flawed saying it does not correct for important differences in those who do and those who do not undergo A-Fib ablation.]


Dr. Calkins cited a study comparing Radiofrequency Ablation vs. Antiarrhythmic Drugs as First-line Treatment of Symptomatic Atrial Fibrillation. The A-Fib free success rate was significantly higher for catheter ablation. The study concluded “Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF.”2

But what about possible complications from catheter ablation? [For a more extensive discussion of this topic, see Dr. Keane’s earlier Symposium presentation Risk of Complications from a Catheter Ablation.] Dr. Calkins discussed the RAAFT 2 randomized clinical trial. The CA study found a 7.7% complication rate compared to 19% for patients on antiarrhythmics (AADs). The success rate for CA was 45% [low compared to other studies], while the success rate for AADs was only 28%. In the AAQD study, 59% had to stop at least one drug and nearly half did choose to have a catheter ablation.

In another study, the overall complication rate was 6.9% in patients undergoing AF ablation. But more importantly, the study concluded “there was a significant association between operator and hospital volume and adverse outcomes.”3


•  The guidelines have gotten it right.

•  It is difficult to advise that all patients undergo AF ablation as first line therapy given that AF ablation is associated with a significant risk of major complications including death.

•  Clearly a patient’s values and preferences play a big role.

•  But of equal importance is the operator’s own data on success and complications.

•  There is increasing evidence that experience matters when it comes to the outcomes of AF ablation. Most experienced operators have waiting lists.

•  While waiting for an experienced operator, you might as well try an AA drug.

•  It is my impression that the Guidelines are being adhered to. Most patients undergoing ablation today have failed at least one antiarrhythmic medication and have symptomatic AF.

•  Consistent with the guidelines, in rare situations select patients are undergoing ablation as first line therapy.

•  Some asymptomatic or minimally symptomatic patients are undergoing ablation for “theoretical reasons”. “In my mind, this is acceptable provided adequate informed consent has been obtained and patients are aware that the only proven benefit of AF ablation is to improve quality of life.”

Editor’s Comments:
Problems With Today’s Antiarrhythmic Meds
Doctors know all too well that today’s antiarrhythmic meds don’t work very well, or they have bad side effects, or they lose their effectiveness over time. They also tend to cause more and more lasting adverse events than catheter ablation. It’s often safer to have an ablation than to not have one. And the complications from a catheter ablation are most often temporary as compared to living a life in A-Fib or on A-Fib meds.
Also, one of the main reasons people have a catheter ablation is so that they don’t have to take antiarrhythmic meds and anticoagulants for the rest of their lives.
Catheter Ablation First-Line Choice
Today’s guidelines happily take into account these realities. According to current guidelines, you don’t have to spend months or a year trying various antiarrhythmic meds while your A-Fib gets worse, your heart develops more fibrosis, “remodels” itself, and your quality of life is in the toilet.
Then why did 79% of the attendees not recommend A-Fib ablation as first-line therapy? Because, even though catheter ablation is a low risk procedure, it isn’t risk free. The risk is similar to having your tubes tied, i.e. 1-2%. (By comparison, the risks of an appendectomy are around 18%.)
Know Your Rights—Be Assertive
As an A-Fib patient, you should know your rights and be assertive—that according to the guidelines, you have a right to choose catheter ablation as your first choice. Your doctor may try to talk you into first trying antiarrhythmic meds before offering you the option of a catheter ablation.
(The author frequently hears of Cardiologists who refuse to refer patients for a catheter ablation, who tell patients a catheter ablation is unproven and dangerous. When you hear something like that, it’s time to get a second opinion and/or change doctors.)
Current guidelines “recommend” catheter ablation or say it is a “reasonable” option.
Catheter Ablation for Patients Without Symptoms
Dr. Calkins, who headed the committee which drafted the guidelines, goes even further. Patients without symptoms or with minimum symptoms can get a catheter ablation.
”In my mind this is acceptable provided adequate informed consent has been obtained and patients are aware that the only proven benefit of AF ablation is to improve quality of life.”
Side note: It’s questionable whether anyone with A-Fib is really symptom-free. If you have A-Fib, the upper parts of your heart (the atria) aren’t pumping properly. Your body and brain are losing 15% or more of their normal blood flow. People get used to it or they write off the increased fatigue, tiredness, mental slowness, etc. as old age. But anyone with A-Fib is affected by it to some extent.
If you have A-Fib and are symptom-free, you have the option of simply living out the rest of your life in A-Fib. But some people may not be able to do this without worrying about it, e.g., “How is A-Fib affecting my heart, how much fibrosis am I developing, how is my heart remodeling over time?” Realize that you can choose to have a catheter ablation for what Dr. Calkins terms “theoretical reasons”.

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Last updated: Wednesday, September 2, 2015 


Footnote Citations    (↵ returns to text)

  1. Epstein AE, et al. 2012 ACCF/AHA/HRS Focused Update Incorporated Into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2013; 127: e283-e352 doi: 10.1161/CIR.0b013e318276ce9b
  2. Wazni OM, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005 Jun 1;293(21):2634-40. doi:10.1001/jama.293.21.2634.
  3. Abhishek, D. et al. In-Hospital Complications Associated With Catheter Ablation of Atrial Fibrillation in the US between 2000 and 2010: Analysis of 937,810 Procedures. Circulation. 2013;128:2104-2112. doi: 10.1161/CIRCULATIONAHA.113.003862

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