Enlightened Medical Management of Atrial Fibrillation, Part II: The Pill In The Pocket Approach

It has been estimated that patients with paroxysmal atrial fibrillation (PAF) have health care costs 5 times those without  afib. More than 50% of those costs are attributed to ER visits and acute care hospitalizations. The pill in the pocket (PIP)  approach can substantially reduce those hospital visits.
PIP addresses the complimentary patient priorities of minimizing daily drug burden and empowering patients to self-manage their episodes of sustained PAF thereby reducing the need to visit the ER or be hospitalized.

How Doth The Pill In Pocket Work?

With this approach, the patient upon experiencing a symptomatic episode of atrial fib takes (or as we doctors like to say “self-administers”) a single bolus of oral flecainide or propafenone (two so-called antiarrhythmic drugs or AADs.)
It is not necessary that the pill be in the pocket of the patient, indeed the pill might be in the pocket of the pastor of the patient or perhaps in the purse of the paramour of the patient. Indeed, the pill only need be near enough that the patient can pop it into his or her pie hole within a reasonable time period after the AF begins.
In properly selected patients, generally within 3 hours, the rhythm will suddenly pop back to normal
Prior to popping the AAD pill it is wise to have the patient pop a pill that slows the heart rate such as a beta blocker or cardizem or verapamil.
After popping the pill it wise to have the patient assume a supine position or at least a sitting position for a few hours or until the heart pops back to normal.

One Man And One Woman’s PIP Experience

I first saw Pete in 2017 on the day after his 60th birthday.  He awoke in the middle of the night feeling his heart fluttering. He was weak  and very light headed and came to our ER where he was noted to be in rapid atrial fibrillation.
He was given intravenous  cardizem which slowed his heart rate and made him feel better but did not convert him back to normal rhythm. We started him on the newer oral anticoagulant, Eliquis, to reduce his stroke risk.
The next day I performed a cardioversion on him after excluding the presence of left atrial thrombus with a transesophageal echocardiogram.
He did well for some time without recurrent afib but two years later he was again awoken from sleep around 1130 PM with a feeling of his heart fluttering and shortness of breath.
In the ER afib with rapid ventricular response was again noted and this time the ER doctor suggested that an electrical cardioversion be performed right away. Pete was told  there were “slight risks” to the procedure but he was nervous about doing it without me being on the case. His heart rate  was 106 and he was given an intravenous beta-blocker,  metoprolol to slow the heart rate.
The next morning we discussed options with him and decided to try the PIP approach to convert him back to normal rhythm. He received 300 mg flecainide orally at 11 AM and 1.5 hours later he converted to the normal rhythm.. The monitor strips recorded below captured the transition nicely.
pill in pocket flecainide
A 72 year old woman whom we shall call Miss Mystery X  presented with a sensation of weakness and dizziness beginning at noon. She had a history of paroxysmal afib. We had her come into office and ECG demonstrated atrial fibrillation at a rate of 100 BPM.
She was admitted to telemetry and given 300 mg flecainide and 45 minutes later the telemetry ECG strip below indicated conversion to normal sinus rhythm without any pauses, symptoms or hypotension. We discharged her later that day.
For both of these patients we have carefully documented that they have a structurally normal heart by echocardiography and stress testing which is essential when utilizing flecainide. In addition, we carefully assess for stroke risk and anticoagulate them accordingly.
They now have available as outpatients a method for converting from afib to SR which is proven safe and effective for them.
I recently saw Miss X in the office after her hospital visit. She had just returned from a trip to Peru and Bolivia. Among other fascinating adventures she had flown over the Nazca Lines.

Aerial view of the “Heron”, one of the geoglyphs of the Nazca Lines, which are located in the Nazca Desert, near the city of Nazca, in southern Peru. The geoglyphs of this UNESCO World Heritage Site (since 1994) are spread over a 80 km (50 mi) plateau between the towns of Nazca and Palpa and are, according to some studies, between 500 B.C. and 500 A.D. old. Courtesy Wikimedia Commons.

Fortunately, she had no episodes of afib but should she have started fibrillating she knew that she had a safe and effective treatment that could convert her back to normal without the need of engaging foreign doctors and hospitals.
One of these two patients has acquired  the AliveCor Kardia Mobile ECG and will have the capability of transmitting to me his ECG via KardiaPro should his device alert him to the presence of atrial fibrillation. This capability further enhances the control that patient’s can have over the diagnosis and treatment of their afib episodes

The Science Behind The PIP Approach

The seminal article on the PIP approach was published in the New England Journal of Medicine in 2004 by Alboni, et al.
The paper reported on 268 patients with PAF presenting to the ER who had a structurally normal heart and were without disabling symptoms or low BP who were given larges oral doses of oral flecainide or propafenone. Overall, 210 patients converted to normal rhythm and were felt appropriate for out patient treatment.
This approach was quite successful:

During a mean follow-up of 15±5 months, 165 patients (79 percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92 percent) were treated 36±93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94 percent); the time to resolution of symptoms was 113±84 minutes.

ER visits and hospitalizations for PAF were markedly reduced.
I tracked down Dr. Alboni through the scientific research social media site ResearchGate.net and asked him if he was still utilizing this approach and if he had any new data.
He responded.

the follow-up was terminated as reported in the paper. However, I have then observed that in patients > 75 years there are many side effects (unpublished data) and I do not utilize anymore the pill-in-the-pocket approach in these patients. I am still using flecainide and propafenone according to the doses and the methods described in the paper.

His 2004 paper enrolled patients 18 to 75 years of age and I have tended to restrict the PIP approach to my patients under age 76 due to concerns about more conduction disease and occult CAD in older patients.

When I pressed Dr. Alboni for more data or info on this he responded:
  • I observed a high incidence of side effects in patients > 75 years in the daily clinical practice, but I did not carry out a research because, after a concentration of side effects in a few patients, I did not prescribe anymore this treatment to old patients

PIP Current Practice

There is a nice paper on recent experience with the PIP approach which was published in 2018 by Josh Andrade who runs a multidisciplinary AF clinic in Vancouver, Canada

Consecutive patients aged 18-75 years of age attending the Vancouver multidisciplinary AF clinic and receiving PIP treatment were studied over a 3 year period. Entry criteria included, sustained symptomatic episode lasting >2 hours, frequency <1/month, absence of severe or disabling symptoms with AF episode
Patients with significant structural heart disease (LVEF<50%, “active ischemic heart disease”, severe LVH) were excluded along with those with the following features:
-Abnormal conduction (QRS>120ms, pr>200 ms, pre excitation)
-Clinical or ECG evidence of sinus node dysfunction/bradycardia or AV block
-hypotension with systolic blood pressure <100 mm Hg
Participating patients received their first PIP treatment while being monitored on telemetry in either an ER or hospital telemetry.  They were given the instructions below to give to the doctors in the ER.
Vancouver PIP sheet1
And they were provided with these instructions:
PIP vancouver 2

As the graph below shows, the PIP  approach resulted in a substantial reduction in ER visits, as well as a substantial reduction in the need for electrical or IV pharmacologic cardioversions

Adverse events (mostly low blood pressure but also 2 cases of conversion of  rhythm to a more rapid atrial flutter requiring cardio version) were noted in 16% of the initial PIP-AAD administrations and 19% failed to convert to NSR.
The Andrade PIP approach has patients receive a single dose of a rate-slowing drug 30 minutes prior to giving the AAD. This was done to prevent 1:1 conduction of atypical flutter. It’s not clear if this is beneficial and it could potentially contribute to episodes of bradycardia or hypotension.
In my practice I utilize flecainide over propafenone exclusively for both PIP therapy and chronic maintenance therapy. The generic version of flecainide for chronic therapy is twice daily versus thrice daily for propafenone and therefore preferred.  Dr. Andrade told me that when using the PIP approach:

In our clinic it’s probably 60:40 Propafenone to Flecainide.

Pill In The Pocket: Another Tool in The Toolkit For Enlightened Medical Management of Atrial Fibrillation

For the patient with PAF and relatively infrequent episodes of symptomatic afib the PIP approach can be very useful. Once established as safe and effective it allows the patient to avoid ER and hospital visits related to the PAF.

The ideal patient is less than 76 years of age and has a structurally normal heart.
PIP works really well for patients who are armed (pun intended) with a way to monitor their rhythm such as Apple Watch 4 or AliveCor’s Kardia Mobile ECG. Use of personal ECG monitoring in conjunction with a cardiologist practicing Enlightened Medical Management of afib is the optimal approach.
ProPIPically Yours,

12 thoughts on “Enlightened Medical Management of Atrial Fibrillation, Part II: The Pill In The Pocket Approach”

  1. Hi Dr. A!
    I was put on flecainide both as a PIP and with regular dosing before my first AF ablation about seven years ago. When that didn’t keep the episodes away, propafenone was tried both ways. Neither prevented the devastatingly symptomatic three to five hour episodes.
    My cryoablation stopped AF!
    My second ablation stopped Flutter.
    My third ablation stopped atrial tachycardia.
    In lieu of more ablation, dofetilide (Ticosyn) was tried against further atrial tachycardia. (Requiring that three day hospital stay you mentioned for sotalol.) Two and a half months without tachycardia can’t be counted as a success!
    After an episode of 202 beat per minute 1:1 on Friday the 13th of this month, I had my fourth ablation. Seems there was a rotor on my septum.
    Feeling much better now!
    (Trying not to wait for the fifth “shoe” to drop!)

    • Now, the interesting but difficult question:
      To what degree might my arrhythmias subsequent to the ablation for AF been iatrogenic?
      For example, might my recent septal rotor have resulted from a previous puncture, getting the catheter and such from right to left?

  2. Terrific article, thank you. As a lone afib (I believe that is the correct term) patient, I would very much like to be off of the twice day regiment of flecainide 100mg. Would you consider the PIP treatment an option for a patient experiencing 2-3 afib episodes a year even while under preventive meds? I would assume the episodes would increase?
    Currently they are generally short in duration and, as they always happen early in the morning, they will go away within an hour or so of taking my scheduled a.m. dose. I am also working on losing excess weight as I discovered an interesting article earlier this year on the positive results of weight loss on the frequency of afib episodes. Unfortunately the Australian study was old and I have not been able to find anything newer.
    Thanks for your well thought out articles and the passion you bring to the topic.
    – Julie, Louisiana

    • Julie,
      The term “lone afib” has fallen out of favor in the last decade. But the concept of a youngish patient with afib who has a structurally normal heart is basically the same. And these patients are the best candidates for PIP.
      I’m working on my manifesto on flecainide for chronic afib prophylaxis. I use quite a bit of it.
      I think what you are asking about is chronic flecainide therapy versus PIP flecainide.
      I would presume if you stop the daily oral flecainide therapy the episodes would increase based on your description of current episodes happening in early AM and going away shortly after taking your flecainide dosage.
      I have found in some patients a tendency to go into afib if they miss a dose of flecainide or it is delayed for some reason. I counsel them to take it q 12 hours meaning upon arising and then 12 hours later.
      Working on weight loss is a great idea.
      Dr P

      • Hi … is 54 youngish? LOL. I am on the 12 hour cycle you mention. I would love to be off it. Of course i know the nervousness of being off the meds and “waiting” for an episode would probably send me into afib. Thanks again for your dedication to the topic. I do have the Kardia and love the since of control and knowledge it gives me. My EP likes them as well. Julie

        • 54 is most decidedly youngish! For those patients who have frequent AF episodes nearing the end of the 12 hour effectiveness of flecainide we will often trial a higher dosage. Higher dosage translates to higher blood levels 12 hours after the dosage. So happy to ear your EP appreciates Kardia. I find most consider it a nuisance.

  3. sadly, my husband who has had PAF for two years (one episode about every 6 months) and was sentenced to a “wait it out” treatment regimen (usually he converted somewhere between 3 and 10 hours so “there’s nothing to do”) was unable to benefit from the pill in a pocket when someone finally prescribed it. He has a structurally sound heart etc — the problem is that it just didn’t work. He used propafanone the first time and it didn’t work; since he couldn’t get an answer from the cardiologists office he tried again in 24 hours, still didn’t work. Finally two day later he converted on his own at about the time that the office returned his call. The second time the propafanone didn’t work (over a weekend again of course) and he didn’t self convert either, so he took the advice of his cardiologist to go to the ER for cardioversion on Monday since we were out of town. At which time the ER doc told him that because his rate was already controlled by his daily carvedilol, he was not sick enough to cardiovert, and the consulting cardiologist with the ER told him to come to his office in 4 days for cardioversion if a trial dose of flecainide 100mg bid didn’t convert him. It didn’t — So finally after putting up with misery for 6 days they cardioverted him as an outpatient at the cardiology office and put him on a daily “preventative” dose of flecainide 100 bid. The doc told him that if his Afib “breaks through” the daily flecainide then his “only other option” would be ablation.

  4. Good article. My issue with using flecainide and propafenone is the stress testing requirement. Occasionally the stress test is abnormal which then leads to cardiac catheterization followed by revascularization in asymptomatic patient which may actually do harm. Sotalol does not have this requirement. Why do you prefer flecainide over sotalol? Thanks.

    • I have found sotalol to have unacceptably high incidence of side effects related to its strong beta-blocker component. I am also concerned more about proarrhythmia with sotalol (torsade des pointes VT) than flecainide. Sotalol is expensive in the US and requires 3 days loading in hospital whereas flecainide is generic and cheap and can be started as an outpatient. Many patients have fluctuating renal function and sotalol is very dependent on kidney function for elimination which can be problematic.
      And finally, sotalol is no more effective than flecainide.
      I agree with your concerns about downstream adverse consequences of stress testing in the asymptomatic patient. There really isn’t any unanimity or consensus on stress testing in patients on flecainide. What is your protocol and why?


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