The patient is anxiously sitting on the exam table. A notebook, a pencil and many papers from the internet and other doctors are close at hand. A spouse sits in the accompanying chair with an equally anxious face that says without words, “please help us out here.”
The problem at hand is atrial fibrillation. Paroxysms of frighteningly rapid heart racing occur at random. They defy even the most diligently kept log books. Unpredictability and fear enhance the discomfort of these already highly bothersome spasms. Normal life is displaced. Pleasurable endeavors as simple as eating, or exercise, and even travel are suspended. Normal life is gone.
AF does this frequently. Patients desire objective (real) relief. That stroke or heart failure risk are minimized is good, but these important therapeutic goals take a backseat for symptomatic patients. “I need help,” cries out the symptomatic AF patient.
The toolbox to deal with AF has expanded dramatically over the past decade. This is good news. Catheter ablation of atrial fibrillation is one of these newly honed tools, albeit a large hammer. A recent addition to the AF toolbox is the once promising new drug, dronedarone (Multaq). It is from Sanofi-Aventis. When released last July, there was much fanfare, like a baseball team that had a promising spring campaign.
Dronedarone is a metabolite of our most effective AF drug, amiodarone. Although amiodarone is statistically the most effective pharmacologic suppressor of AF, it has many downsides. These include its side effects: gastrointestinal intolerance, CNS issues like insomnia and ataxia, photosensitivity, and bradycardia often prompting the need for a permanent pacemaker. In addition to side effects there are also potential organ toxicities: thyroid abnormalities, liver enzyme elevations, and the the most feared complication, pulmonary fibrosis–which can be irreversible.
Dronedarone was originally marketed as amiodarone without the adverse effects–“amio-lite.” Exciting. If only it worked.
What are you talking about? There are DMV-sized lines of distinguished professors touting dronedarone’s role in AF treatment.
Yes, there is the ATHENA trial which showed that dronedarone reduced hospitalizations from cardiovascular events in patients with AF. The study also confirmed a lack of harm from dronedarone. Unfortunately, its efficacy in actually suppressing AF was slightly less than modest. This is bad news for the symptomatic patients who desperately desire a fix. Reducing hospitalization is a neat endpoint, but it does not equal fixing a patient’s AF.
I could tell the above patient and spouse, “here is a new medicine for AF.”
“Is it really good,” the patient asks with hopeful eyes.
I could say, “Well, it really won’t suppress your AF, but it will reduce the statistical likelihood of being hospitalized for AF.”
Unfortunately, real-life experience with dronedarone has confirmed its lack of anti-arrhythmic efficacy. In nine months of using dronedarone, I am batting zero–not a single success story. My non-industry sponsored EP colleagues echo the same depressing experience. The experts say, “its AF suppression is modest.” How about, “as yet, it doesn’t work.”
Not only has dronedarone proven ineffective in suppressing AF, it is often associated with adverse effects. I have thus far seen GI intolerance, excessive bradycardia and QT prolongation. And as with all newly released drugs, dronedarone is incredibly expensive.
Our success as doctors depend on the use of tools that work. It is true that all AF drugs have limited effectiveness, and all have narrow therapeutic windows that mandate skill in their use. It isn’t always, but for the other anti-arrhythmic medicines, at least sometimes, they actually work. Patients like this. Doctors do as well.
My chapter on dronedarone is not yet closed. I remain open-minded; admittedly my denominator of dronedarone experience needs to be larger before rendering a more definitive conclusion.
By describing this sobering initial impression of dronedarone–unlike the Cedars-Sinai group–I am not advocating the use of amiodarone. There are far more elegant strategies available than the widespread use of amiodarone.
My amiodarone-avoidance-approach for AF therapy goes something along the lines of: Frame the problem. Educate. Reassure. Empathize. Always avoid making the treatment worse than the disease. This tenet is often overlooked. In many cases, using amiodarone seems a good example of making therapy worse than the disease. I wouldn’t take it myself, so it is hard to recommend for a patient.
Therefore, for me, recent studies describing how to switch a patient from amiodarone to dronedarone are mostly irrelevant.
Like it once did in the treatment of SVT and WPW, catheter ablation in the left atrium, has changed my approach to treating AF. Knowing that ablation can be performed effectively and safely changes the paradigm for therapy. Being comfortable with ablation makes one less dependent on medicine. Not that ablation can replace medicine, just that the playing field is less skewed against catheter ablation.
Additionally, the widespread use of CRT pacing has improved our ability to palliate symptomatic tachycardia without medicine.
Finally, and most poorly compensated for, is the doctor-patient relationship. The time spent educating, empathizing and framing the AF problem cannot be quantified in studies, but surely plays a major role in helping the patient live alongside the beast that is AF. Knowing helps people.
Using expensive medicine is acceptable if they work better than these other treatment strategies. So far, dronedarone is not looking like a shining star. We will see.
Just a dose of reality from the real world.
9 replies on “A real world view of new developments in the treatment of atrial fibrillationâ€¦”
Hi, practicing EP not sponsored by multaq.
I shared your initial reluctance about multaq. In fact the bulk of my patients were started by aforementioned sponsor physicians. i am not sure how to interpret your comments.
i have had some success and many side effects.
by some success i mean there are patients that i have to periodically cardiovert from af, like most of my aad patients. they seem to have less episodes than before when i monitor them periodically. certainly they are less symptomatic.
i spend a lot of time educating the patients. most of my ablation patients consults get talked out of it after discussion of side effects and what to expect after few years. the likelihood of recurrence, in my view, is very high no matter what treatment modality you opt for, even for true paroxysmal patients. after we get into cost of ablation, almost every patient swallows hard. does insurance cover the vast majority of cost for AF ablation where you work?
i have patients in whom i don't want to ablate-high CHADS2 score or very elderly, with mild heart failure. for them, if we exclude amiodarone, options are limited. when presented with tikosyn or multaq, which as you know are both expensive, they frequently choose multaq because it doesn't require admission. has your experience been that tikosyn is more 'successful' than multaq at suppressing af? i guess i'm curious as to how you define success!
Thanks for the thoughtful words.
Insurance does cover ablation here. Our experience has been like others: it isn't SVT ablation, but many patients have AF eliminated, or at least better controlled with meds.
You are right about the elderly. I have yet to ablate anyone in their eighties. I do use some Amio–almost exclusively in the highly symptomatic myopathy patient.
I find dofetilide very useful. Yes, it does require a hospital stay, and careful attention to the QT, but it works in many cases. For some reason, it is especially helpful after PVI. Also, dofetilide, and to a lesser extent Sotalol, can change persistent fibrillation to intermittent fib, which then facilitates ablation.
AF treatment is a journey. Success is defined as an improved patient. Many are off medicine, but those that aren't are still improved if there AF episodes are lessened.
Dr. John, I was fascinated by your take on Multaq. Here's a serious cyclist's experience with it.
I'll admit to not being a "pill" type patient. This is especially the case if I think a long-term medication will adversely affect my cycling. However, in Dec. '09, per my EP's recommendation, I started on a low dose of Multaq in an attempt to treat late recurrent paroxysmal A-Fib and to see if it would help alleviate debilitating ectoptic beats. He's told me on at least four occasions that an ablation will not get rid of ectopic beats. I may be only a lowly engineer, but I get it and, as I've had 7 A-Fib episodes since my ablation 18 months ago, I wonder where we're going with my course of treatment. Nevertheless, I agreed to give Multaq a try.
I rode-out some common Multaq side-effects, such as GI upset. lethargy, and rash, but at the advise of my PCP, started and stopped the medication twice over the past 4 months for various other reasons. At the end of January, the EP had me go back on Multaq, as the arrhythmia symptoms were worsening. However, two days ago, my he took me off it for good, as the these symptoms had gotten even worse: two A-Fib episodes in a week and increased ectopic beats, including long periods of bigeminy. I was also getting even more short of breath while cycling or walking uphill. An EKG done last week, after I'd ramped-up to a full dose, showed arrhythmia (bigeminy,I believe)and a prolonged QTc. Within a day of going off the drug, my symptoms have lessened considerably , but as in the past, I feel more A-Fib could be right around the corner.
So, I gave Multaq a try. At first it helped somewhat to reduce ectopic beats, but in the end, it worsened them, so the drug wasn't the right one for me. Now I've agreed to start a low dose of propafenone. I'm trying not to pre-judge it for possible side-effects. Too bad this is happening just as the weather is finally getting nice for cycling.
As an American living in the UK I am fascinated to read your take on Multaq. NICE here is just about to approve Multaq for use on the NHS and as a PAF sufferer I have been anxiously awaiting it ! However, I was not aware of the side effects/ineffectiveness before I read your blog. I am only 41 and have had PAF for just about two years with my episodes now every single day ( mostly on and off all night but now creeping into the daytime hours) and have begun to consider an ablation as a possibility. I will now consider it more seriously as in reality there doesn't seem to be the perfect pill.
I was on Multac pre and post cardioversion but my Afib returned after a few weeks. I would say the multaq had no effect what so ever.
Thanks for sharing your stories of AF. They each illustrate the seemingly infinite ways that AF affects us. It is an evolving story–for sure.
Great to hear comments that favor an honest look at Multaq. The overly glowing reports always seemed too good to be true. My mother developed peripheral neuropathy while on it. Her doctor admitted that this is a side effect of amiodarone which is multaq's "parent"—-so multaq could well cause this also. It's only been out a short while. what other side effects may pop up that haven't initially? We'll know–some day perhaps. In my mom's case–she is abruptly discontinuing it–and we'll see if her problem improves.
Dear Dr John
Thanks for your very interesting take on new treatments for AFIB. I have had it for about 5 years and it has steadily progressed to the point where I get it every 5-8 days. It is a very debilitating condition and I'm sorry for everyone who suffers it. I live in constant fear of dying or having a stroke. I try to be 'brave' but I live by myself,and the closest hospital is a good 40 min drive, and that is if you can drive yourself. If you need to wait for an ambulance bad luck. I take (with trepidation)Flecainide and recently have upped the dose to 50mg bx2 daily. Since doing that I have had kidney pain dizziness and nausea.I have a question re my gut. About 15 years ago I had Fundoplacation(not sure if spelling correct)
surgery. I have been told about 5 years ago the wrap had slipped upwards and my hiatus hernia had returned as well.I believe one of my biggest triggers for AF is eating, followed by bending over and laying on left side. I have often felt as if my gut was in my chest. My question…is there a possibility that my stomach/hernia can be pushing against my heart and causing my AF.I have googled the question and it seems there is some evidence this maybe be so. I live in Australia and over here most doctors think you are a pain in the neck if you worry about your AF. I was put on Flecainide without any monitoring, just given a script and told to go for it. Any advice would be very welcome. Joy W
I have had intermittent A. Fib for the last few years. I have had to have two cardioversions. I started on Multaq this June and while on the drug had no recognized A. Fib. I am a bicyclist and found my heart rate dropped about 10-15 beats from my max rate and I had some reduced ability to climb hills. So I lowered the dose and got A. Fib.. I restarted and so far no A. Fib.. My only issue is the modest reduction in exercise tolerance. I am considering ablation but I am not fully sold on it. So right now I am continuing on the Multaq.