Letter from the Editor in Chief

DOI: 10.19102/icrm.2012.030301

John Day, MD, FHRS, FACC

Editor-in-Chief

Dear Readers,

Within this month’s Letter I would like to focus on the excellent manuscript submitted by Michael Kim, entitled “Concepts in Disease Progression of Atrial Fibrillation and Implications for Medical Management,” which may be found in the Atrial Fibrillation (AF) section of this issue. In this article, Dr. Kim takes us through the entire aspect of AF management, from mechanisms to potential therapeutic implications. I highly recommend this article for your review. Please feel free to share this with staff and colleagues as well.

There are a few aspects of this article that I would like to comment on and offer opinions from personal experiences. In particular, I would like to touch upon how to prevent AF from occurring, the real toxicities of antiarrhythmics, and the exciting new developments in anticoagulation therapy.

Yes, we are truly witnessing a significant increase in the number of new AF cases diagnosed each year. At our institution, we are noticing a handful of patients each day in our clinic that were diagnosed with new onset AF the night before in the emergency room (ER). While some of these patients are elderly, or may have AF associated with a pulmonary process such as pneumonia or an upper respiratory infection, it seems that most new AF patients we are seeing are later middle age, with hypertension and obesity as the precipitating causes.

As we get bigger and bigger, and become more and more sedentary as a society, this is simply a natural consequence. Indeed, I have seen many cases where AF, hypertension, and sleep apnea have all completely resolved with dramatic weight loss. Unfortunately there is no magic pill or diet that will give us a slim waistline and good health. In fact, patients that fall for these “quick fixes” often wind up in a worse situation. We all know that the real “secret” is to totally commit to a healthy lifestyle, and weight loss will occur as a natural consequence of our commitment to health. As physicians, we need to encourage our patients to get active and eat a primarily whole food, plant based diet (vegetables, fruits, healthy grains, and nuts) with minimal animal products or processed foods. Yes, AF is potentially avoidable- but only with a healthy lifestyle.

Dr. Kim also provides an excellent review of rate versus rhythm control trials utilizing antiarrhythmics. Of particular interest is the review of specific antiarrhythmic strategies, including latest data from dronedarone in the PALLAS Trial. As I reflect on dronedarone, the path this drug has taken over the last 10 years is amazing to me. Initially we hoped this would become the holy grail of antiarrhythmics, as it could offer all of the benefits of amiodarone with none of the serious toxicity. How “dead” wrong we were!

As studies demonstrated the benefits of maintaining sinus rhythm with dronedarone were only slightly better than placebo, we were still eager to prescribe this new antiarrhythmic when it was finally approved in 2009, under the notion that, while it was a “weak” antiarrhythmic, it was at least “safe” for our patients. However, soon after market release there were reports of possible liver failure, which many dismissed. Then there was irrefutable evidence from the PALLAS Study released last year. I am still utterly amazed at the hypothesis of this study- mainly that permanent AF patients, in whom there was no intention of restoring sinus rhythm, could somehow magically have better health by taking an antiarrhythmic. Not surprising, on July 7, 2011, the study was stopped as dronedarone resulted in a two-fold increase risk of death, stroke, and cardiovascular hospitalization when compared to placebo.

So where does this leave us? In our experience, dronedarone is still a weak antiarrhythmic. From a safety profile, it is no safer or more dangerous than any of the other antiarrhythmics currently on the market. AF treatment guidelines in the United States still recommend an antiarrhythmic as first line therapy for symptomatic AF, despite the myriad of toxicities with these drugs. Indeed, many insurance companies in our part of the country refuse to cover AF ablation until the patient has failed an antiarrhythmic. I would argue that the risks of AF ablation are much lower than antiarrhythmic drug therapy at experienced centers. As a large enrolling center in the CABANA Trial, which is comparing medical therapy versus ablation for AF, we have not only seen more adverse events, but more serious adverse events, from antiarrhythmics in comparison to ablation. I suspect the AF guidelines in the United States will likely remain unchanged with regards to first line therapy for AF until the results of the CABANA Trial are available.

The last area I want to touch upon are the new and exciting developments in anticoagulation therapy. I must confess that I have never been a fan of warfarin. The unpredictability of this drug, drug-drug interactions, food-drug interactions, and the frequent blood tests are a nightmare to manage. Nationwide, approximately 40% of warfarin patients are “out of range” at any given time. Even at Intermountain Healthcare, where we have an excellent Coumadin Clinic, in 2011 only 69% of our patients were in a therapeutic INR range.

While we were initially enthusiastic about dabigatran as an alternative to warfarin, we have become progressively less enthusiastic with time as we have seen the dabigatran bleeds, particularly in the elderly with impaired renal function. For many physicians, it takes only one of your patients in the ER with a life-threatening dabigatran bleed to realize that there is absolutely nothing you can do to reverse the anticoagulation. This will certainly change one’s perspective of the drug; such was the case with me. In addition to the non-reversibility of this drug, dyspepsia has been another big challenge at our center. This is particularly worrisome after AF ablation, as the dyspepsia symptoms of dabigatran can mimic those of an acute thermal esophageal injury following AF ablation. We are also concerned that perhaps dabigatran dyspepsia or acid reflux could potentially increase a patient’s risk of esophageal injury following AF ablation.

Fortunately, there is a new option with rivaroxaban. We are particularly excited about this anticoagulant at our center. We like that dyspepsia is not an issue, and that it can be readily reversed with prothrombin complex concentrate. The challenge for us has been educating ER physicians at small community hospitals in our referring area about this antidote, and convincing them to become an advocate in having their hospitals stock this expensive antidote. I suspect that with time, as this medication grows in popularity, stocking prothrombin complex concentrate in the pharmacy will become the standard of care at all small community hospitals. Having said this, I must confess that we have not yet seen our first rivaroxaban bleed- so I cannot personally comment on how effective the prothrombin complex concentrate is.

Is there a downside to rivaroxaban? The data seems to suggest that stopping the drug increases the risk of stroke. In our practice, we stop rivaroxaban 2 full days prior to an ablation or device implantation. In higher risk patients we will bridge them prior to their procedure. However, in lower risk patients we have not seen an increase in stroke with discontinuing the medication two days prior to their procedure. Hopefully there are no new toxicities that will emerge with rivaroxaban, so that we can one day be completely “done” with warfarin.

We hope that you will enjoy this month’s issue of the Journal, and that we can continue to be an important aspect of your ongoing education. As always, we want to hear back from you. Please feel free to email me at any time with your thoughts and suggestions.

Sincerely,

John Day, MD, FHRS, FACC
Editor-in-Chief
The Journal of Innovations in Cardiac Rhythm Management
JDay@InnovationsInCRM.com
Director of Heart Rhythm Services
Intermountain Medical Center
Salt Lake City, UT