It has been estimated that patients with paroxysmal atrial fibrillation (PAF) have health care costs five times those without atrial fibrillation (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 complementary 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 afib takes -- or as we doctors like to say "self-administers" -- a single bolus of an oral antiarrhythmic drug (AAD), flecainide or propafenone (Tambocor or Rythmol).
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. 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 afib begins.
In properly selected patients, the rhythm will suddenly pop back to normal, generally within 3 hours.
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's 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.
PIP Experiences
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 apixaban (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 2 years later he was again awoken from sleep around 11:30 p.m. 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 IV 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 a.m. and 1.5 hours later he converted to the normal rhythm. The monitor strips recorded below captured the transition nicely.
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 the 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 an outpatient method for converting from afib to sinus rhythm, which has 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.
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 patients 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 blood pressure who were given larges oral doses of oral flecainide or propafenone. Overall, 210 patients converted to normal rhythm and were felt appropriate for outpatient treatment.
This approach was quite successful:
"During a mean follow-up of 15±5 months, 165 patients (79%) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92%) were treated 36±93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94%); the time to resolution of symptoms was 113±84 minutes."
ER visits and hospitalizations for PAF were markedly reduced.
I tracked down Paolo Alboni, MD, 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 ages 18 to 75, and I have tended to restrict the PIP approach to my patients under age 76 due to concerns about more conduction disease and occult coronary artery disease 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 published in 2018 by Jason Andrade, MD, who runs a multidisciplinary afib clinic in Vancouver.
Consecutive patients ages 18 to 75 attending the Vancouver multidisciplinary afib clinic and receiving PIP treatment were studied over a 3-year period. Entry criteria included a sustained symptomatic episode lasting >2 hours, frequency <1/month, and absence of severe or disabling symptoms with afib episode.
Patients with significant structural heart disease (left ventricular ejection fraction <50%, "active ischemic heart disease," severe left ventricular hypertrophy) were excluded along with those with the following features:
- Abnormal conduction (QRS >120 ms, PR interval >200 ms, pre-excitation)
- Clinical or ECG evidence of sinus node dysfunction/bradycardia or atrioventricular block
- Hypotension with systolic blood pressure <100 mm Hg
Participating patients received their first PIP treatment while being monitored on telemetry in the ER or hospital. They were given the instructions below to give to the doctors in the ER.
And they were provided with these instructions:
As the graph from the HeartRhythm paper 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 two cases of conversion of rhythm to a more rapid atrial flutter requiring cardioversion) were noted in 16% of the initial PIP-AAD administrations and 19% failed to convert to normal sinus rhythm.
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."
Another Tool in The Toolkit
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 age 76 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 an 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.
I have received no payment -- monetary or otherwise -- from AliveCor, nor do I own any of their stock.
Anthony Pearson, MD, is a private practice noninvasive cardiologist and medical director of echocardiography at St. Luke's Hospital in St. Louis. He blogs on nutrition, cardiac testing, quackery, and other things worthy of skepticism at The Skeptical Cardiologist, where a version of this post first appeared.