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.
But…
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.
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