Tag Archives: flecainide

Enlightened Medical Management of Atrial Fibrillation, Part III: Flecainide for Chronic Suppression

As a practitioner of enlightened medical management of atrial fibrillation the skeptical cardiologist utilizes predominantly two antiarrhythmic drugs: amiodarone and flecainide.

As I outlined in Part I of this series, amiodarone is our most efficacious drug for maintenance of normal sinus rhythm (NSR) but requires close monitoring for long term side effects. It is also the safest antiarrhythmic drug (AAD) for patients with AF who have structural heart  disease.

The AAD I use in AF patients with normal hearts is flecainide.

Flecainide is a class IC AAD  which produces a potent and selective blockade of the cardiac fast inward sodium (Na+) current resulting in conduction slowing.

We don’t utilize flecainide (or any Type IC AAD) in patients with significant coronary artery disease or significantly depressed function of the left ventricle because of concerns about it increasing risk of more dangerous heart rhythms in such patients.

In patients with normal hearts, however, flecainide is very safe, extremely well-tolerated, and reasonably effective at maintaining NSR when combined with significant lifestyle modification.

I have scores of patients who have been maintained in NSR for years to decades with flecainide, therefore I think patients with normal hearts should undergo an adequate trial of this AAD before moving on to ablation.

Chronic Suppression of Atrial Fibrillation

A reader with atrial fibrillation recently submitted his case history which describes a typical scenario for a patient who would be a great candidate for long term flecainide therapy:

I am a 62 year old active male. I play (mostly) non-checking ice hockey 3 times a week and bicycle on off days and have a daily yoga practice. I suffer from Hashimoto’s disease and hypertension. Both are adequately managed with medication. I have been in persistent Afib for about a year, not sure about prior to that, but expect it was paroxysmal for awhile prior to diagnosis. There is no obvious cause. I was immediately put on Diltiazem and Eliquis. A month later I received a successful Cardioversion but at my follow-up a week later it was noted that the Afib had returned and is again persistent. I also had an echocardiogram that did not reveal any valve or muscle abnormalities. The advice at the time was to continue on the Dilt unless symptoms worsened. I was taken off the Eliquis due a risk factor of 1 and my desire to resume hockey. After about three months I noticed more fatigue, occasional dizziness, regular palpitations, etc. so got an appointment for another echo and to see an Electrophysiologist. The results of the echo indicate some structural changes since the last echo. Thus the EP recommended 3 choices: 1. continue with just the Dilt, 2. get a stress test and if OK then go back on Eliquis and add Flecainide for rhythm control and get another Cardioversion, or 3. get back on Eliquis and get an ablation and a Cardioversion. I’m not sure which option to choose. The difference in the two echos didn’t seem too extreme – how long can I go with option 1? Option 2 seems less risky but also less effective. Option 3 has the best results but is more risky. What will be the future of my hockey playing? With options 2 and 3 I;ll take a break while on Eliquis but once I turn 65 my risk will be 2 and I’ll probably be on Eliquis from then on. Can I chance option 1 for 3 years? I check my BP daily and use a KardiaMobile 6L to self-monitor.

The reader’s case history is similar to many of my patients.

He started with brief paroxysms of AF that were self-limiting (paroxysmal AF) but at some point, an episode began that was not self-limiting (persistent AF.)

At this point there are two major decisions for patient and physician: 1) Should a blood thinner be started to reduce the risk of stroke? and 2) Should the patient be left in AF (which generally means AF will be present lifelong , thus permanent- aka longstanding persistent AF) or should we attempt to restore and maintain SR?

I’ve reviewed the decision-making process for anticoagulation here.

The second decision is more complicated, controversial, and requires a good and unbiased conversation between physician and patient about options for maintenance of NSR.

In my post entitled “Why I Favor the Early Restoration and Maintenance of Sinus rhythm For Most Patients with Atrial Fibrillation” I laid out my rationale for trying to restore and maintain SR for most patients. In this 62 year old otherwise very healthy and active individual I would strongly favor a very aggressive approach to maintaining SR.

Enlightened Use of Flecainide To Suppress Atrial Fibrillation


Let’s take the example of Ralph,  a 63-year-old man who I saw first 5 years ago.  At that time he was admitted to the hospital with a prolonged episodes of weakness and rapid heartbeat.  Atrial fibrillation with a high heart rate (rapid ventricular response) was the cause and after starting a blood thinner and slowing his heart rate with intravenous diltiazem we proceeded to electrical cardioversion (ECV).

The cardioversion was successful in converting him back to normal sinus rhythm and he was discharged on oral diltiazem and a blood thinner.

Diltiazem is not an anti-arrhythmic drug and has not been proven to lower the risk of recurrent atrial fibrillation but is used in this situation to slow the patient’s heart rate should atrial fibrillation recur. I tell patients that after a first ECV without adding an AAD it is highly likely that AF will recur but we can’t predict if that will be in 5 days or 5 years. Given this possibility of no recurrent AF for years I generally don’t start an AAD with first ECV.

I highly recommend to all my AF patients the acquisition and use of a mobile Kardia ECG device to monitor their heart rhythm. The Kardia (or Apple Watch if the patient has one) is particularly useful pre and post ECV to alert us to the development of AF.

Ralph noted his heart rate had increased about 7 days after the ECV and his newly acquired Kardia ECG device confirmed AF as the cause.

At this point, we had another patient-physician discussion about the value of maintaining NSR and the therapeutic options. Given the early recurrence of the AF,  just repeating the ECV makes little sense. If he had maintained NSR for 5 years just repeating the ECV would be a reasonable option.

To increase our chances of maintaining NSR I started flecainide 50 mg twice daily. Flecainide can be started as an outpatient (as opposed to sotalol or dofetilide which require 72 hours of monitoring in hospital) and it often converts the patient’s rhythm back to NSR without the need for an ECV.  In addition, flecainide as a generic is cheap and at low dosages extremely well-tolerated without significant side effects.

The starting dosage of 50 mg is low but one of my guiding principles for Enlightened Medical Management of AF (EMMOAF) is to use the lowest effective dosage of AAD possible in order to minimize adverse effects.

After 5 days on flecainide, an ECG showed normal  QRS and QT intervals but AF persisted and we performed another ECV. After this ECV, the patient remained in NSR for 2 weeks but again noted high heart rates and AF had recurred.  Following another discussion I had him increase the flecainide to 100 mg twice daily.

Some patients, again, will convert to NSR upon an increase of the flecainide from 50 to 100 mg twice daily, but Ralph remained in AF and we performed a third ECV.

By this time he had acquired a Kardia device and was able to monitor his rhythm. The higher dosage of flecainide was the dosage that worked for him as he maintained NSR after the ECV and has maintained NSR for 5 years since.

I have scores of patients who have a similar path to Ralphs’s with successful maintenance of NSR on flecainide for many years. Some of them converted without an ECV and some, like Ralph, required 3 ECVs.

If AF recurs after a prolonged period of maintenance of NSR with flecainide, the choices are

  • -Leave in AF and control the rate
  • -Leave flecainide at current dosage and repeat ECV
  • -Increase the dosage of flecainide (which may or may not convert rhythm on its own) and repeat ECV at higher dosage.

Enlightened management of these patients who are maintaining NSR on flecainide over many years requires periodic visits (I recommend every 6 months) with an enlightened cardiologist to assess for

  •  any signs or symptoms of structural heart disease
  •  any evidence of proarrhythmia or electrical conduction abnormalities
  •  significant QRS prolongation, ischemia or arrhythmias during exercise stress
  • proper concomitant use of dromotropic (rate-slowing) drugs such as beta-blockers or diltiazem.
  • appropriate use of blood thinners to reduce the risk of stroke or systemic embolism.

When utilized in the manner I’ve described, flecainide usage results in prolonged maintenance of NSR at an extremely low risk of adverse effects in most patients who have structurally normal hearts.

Its effectiveness is greatly increased by patient attention to the eight lifestyle factors that increase the risk of AF and I emphasize these factors to all my patients on a regular basis.

Flecainidingly Yours,

-ACP

N.B. I’ve answered my readers question as to which option I would recommend if he were my patient but not some of his other good questions. Those will be discussed in Part IV of this series. And later I’ll discuss the pros and cons of other AADs for AF.

N.B.2.  For more detailed information on flecainide I recommend this 2015 review in the World Journal of Cardiology

If you are prescribing or taking flecainide it is important to be aware of the CAST trial

(Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324:781–788. [PubMed] [])

 

a seminal study which showed that Type I C AADs are dangerous in patients who have had a myocardial infarction and reduced heart function.

“The publication of the Cardiac Arrhythmia Suppression Trial (CAST) study in 1989, which was designed to investigate the efficacy of class I antiarrhythmic agents moricizine, encainide or flecainide in patients after myocardial infarction with reduced ejection fraction and frequent ventricular ectopic beats, resulted in a major revision of the role of these antiarrhythmic drugs. Thus, while flecainide suppressed ventricular ectopy in those patients, a threefold increase of arrhythmic death was recorded compared to placebo[]. Based on CAST results, flecainide nowadays is not recommended for patients with structural heart disease and coronary artery disease. However, it is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias without structural heart disease”

 

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.

cooks-pip.png

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,

-ACP