Outpatient treatment of recent-onset atrial fibrillation with the “Pill-in-the-Pocket” approach
Open accessAbstract
BACKGROUND: In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation. We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital. METHODS: We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated. Of these patients, 58 (22 percent) were excluded from the study because of treatment failure or side effects. Out-of-hospital self-administration of flecainide or propafenone--the "pill-in-the-pocket" approach--after the onset of heart palpitations was evaluated in the remaining 210 patients (mean age [+/-SD], 59+/-11 years). RESULTS: 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. Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients. The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode (P<0.001 for both comparisons). CONCLUSIONS: In a selected, risk-stratified population of patients with recurrent atrial fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate of compliance by patients, a low rate of adverse events, and a marked reduction in emergency room visits and hospital admissions.
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An alternative to emergency department treatment for patients with infrequent but disabling AF is the pill-in-the-pocket strategy.
“An alternative to emergency department treatment for patients with infrequent but disabling AF is the”
From 2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry (2017) · cites this paper as Alboni et al., 2004
The Conclusions describe patients with infrequent AF episodes that may require emergency-room intervention, and identify pill-in-the-pocket treatment as an alternative. The paper describes those episodes as “well tolerated,” however, rather than disabling; its findings also apply to selected, risk-stratified patients. (LLM, conf=0.84)
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“19,20 Further studies of symptomatic management of AF are needed and may yield reductions in hospitalization events for these patients.”
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“Antiarrhythmic drug 327/694 (47) 192/583 (33) 177/422 (42) ,0.”
Rhythm control in atrial fibrillation
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Newly Diagnosed Atrial Fibrillation
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Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: Rate and Rhythm Management
Gillis, A. M., Verma, A., Talajic, M. R., Nattel, S., & Dorian, P. (2011) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2010.11.001 · Cited by 122 · see citing works
“Oral antiarrhythmic agents such as flecainide and propafenone may be given as single doses (see discussion of “pill in the pocket,” above).(59) Ibutilide is an intravenous class IIImedication that is typically givenas a single dose of 1 mg, which may be repeated once.”
BackgroundQuality of life in patients with atrial fibrillation: how to assess it and how to improve it
Aliot, E., Botto, G. L., Crijns, H. J. G. M., & Kirchhof, P. F. (2014) · EP Europace · doi:10.1093/europace/eut369 · Cited by 123 · see citing works
“The administration of oral antiarrhythmic agents at the time of symptom onset has been shown to be safe and reduces the number of emergency room visits and hospital admissions.(82) Therefore, it seems obvious that the earlier the AF can be treated, the higher the impact of treatment on QoL.”
BackgroundSelf-citationBrandes, A., Crijns, H. J. G. M., Rienstra, M., Kirchhof, P. F., Grove, E. L., Pedersen, K. B., & Gelder, I. C. V. (2020) · EP Europace · doi:10.1093/europace/euaa057 · Cited by 122 · see citing works
“may also be given orally using specific dosing schemes, including pillin-the-pocket.(33,34) Atrial flutter responds to Class III AAD, while”
MethodChyou, J. Y., Barkoudah, E., Dukes, J. W., Goldstein, L. B., Joglar, J. A., Lee, A. M., Lubitz, S. A., Marill, K. A., Sneed, K., Streur, M. M., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001133 · Cited by 125 · see citing works
Treatment of Atrial Fibrillation
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Steinberg, J. S., Varma, N., Cygankiewicz, I., Aziz, P. F., Balsam, P., Baranchuk, A. M., Cantillon, D. J., Dilaveris, P., Dubner, S., El‐Sherif, N., et al. (2017) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.12447 · Cited by 118 · see citing works
“An alternative to emergency department treatment for patients with infrequent but disabling AF is the “pill- inthe- pocket” strategy (Alboni et al., 2004).”
BackgroundStiell, I. G., Clement, C. M., Perry, J. J., Vaillancourt, C., Symington, C., Dickinson, G. E., Birnie, D. H., & Green, M. S. (2010) · Canadian Journal of Emergency Medicine · doi:10.1017/s1481803500012227 · Cited by 117 · see citing works
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Kirchhof, P. F., Bax, J. J., Blomstrom-Lundquist, C., Calkins, H., Camm, A. J., Cappato, R., Cosío, F. G., Crijns, H. J. G. M., Diener, H., Goette, A., et al. (2009) · EP Europace · doi:10.1093/europace/eup124 · Cited by 110 · see citing works
“after cardioversion or post-operatively.(91,92) Other existing concepts use drugs for immediate conversion of AF (e.”
BackgroundState of the Art Review: Atrial Fibrillation in Athletes
Flannery, D., Kalman, J. M., Sanders, P., & Gerche, A. L. (2017) · Heart Lung and Circulation · doi:10.1016/j.hlc.2017.05.132 · Cited by 111 · see citing works
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Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation
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Management of atrial fibrillation: Figure 1
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“In patients with paroxysmal AF who have infrequent paroxysms or few symptoms, or where symptoms are induced by known precipitants (for example, alcohol, caffeine), a “no drug treatment” strategy or a “pill-in-the-pocket” strategy could be considered.”
BackgroundMerino, J. L., Tamargo, J. L., Blomström‐Lundqvist, C., Boriani, G., Crijns, H. J. G. M., Dobrev, D., Goette, A., Hohnloser, S. H., Naccarelli, G. V., Reiffel, J. A., et al. (2025) · EP Europace · doi:10.1093/europace/euaf076 · Cited by 105 · see citing works
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Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation
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“The efficacy and safety of ‘pill-in-the-pocket’ therapy with flecainide and propafenone in an out-of-hospital setting was tested in 210 patients.(30) Of 618 total episodes of AF, treatment was successful in 534 (94%), and the mean time to resolution of symptoms was 2 h.”
Hybrid thoracoscopic and transvenous catheter ablation of atrial fibrillation
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“Despite being often inadequate, medical treatment is still considered the ‘first-step’ approach [2, 3].”
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Drug‐Induced QT‐Interval Prolongation: Considerations for Clinicians
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Use of Flecainide for the Treatment of Atrial Fibrillation
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New developments in atrial antiarrhythmic drug therapy
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“Anti-AF drugs can be very effective in the short term, with up to 80–90% efficacy for the termination of paroxysmal AF and some forms of persistent AF”
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“Although chronic therapy is the rule, intermittent therapy when symptoms arise has been used successfully in selected patient”
MethodSuppression of Spontaneous Ca Elevations Prevents Atrial Fibrillation in Calsequestrin 2-Null Hearts
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Pharmacologic Management of Atrial Fibrillation: Established and Emerging Options
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Self-citation2020 ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease
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“The ‘pill-in-the-pocket’ strategy is frequently used in Europe.(12) Perhaps not surprisingly, amiodarone is still used in a large proportion of centres, but it is usually selected for sick patients with significant structural heart disease, including coronary artery disease and heart failure, in whom immediate CV is n…”
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- Authors
- Alboni, P., Botto, G. L., Baldi, N., Luzi, M., Russo, V., Gianfranchi, L., Marchi, P., Calzolari, M., Solano, A., Baroffio, R., & Gaggioli, G.
- Affiliations
- Ospedale Sant'Anna (IT)
- Ospedale SS. Annunziata (IT)
- Santa Maria Nuova Hospital (IT)
- ORCID
- Botto, Giovanni L.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-12-02
- Volume
- 351
- Issue
- 23
- Pages
- 2384-2391
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2026137049
- Cited by
- 479
- References
- 28
- Citations by year
- 2026: 15 · 2025: 11 · 2024: 18 · 2023: 19 · 2022: 16 · 2021: 21 · 2020: 21 · 2019: 10 · 2018: 18 · 2017: 22 · 2016: 25 · 2015: 20 · 2014: 31 · 2013: 23 · 2012: 20
- FWCI
- 16.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- atrial fibrillation, flecainide, propafenone, oral loading dose, outpatient care, self-administration, sinus rhythm restoration, emergency department visits, hospitalization reduction, adverse drug reactions, atrial flutter
- MeSH terms
- Administration, Oral, Ambulatory Care, Anti-Arrhythmia Agents, Atrial Fibrillation, Feasibility Studies, Female, Flecainide, Follow-Up Studies, Heart Failure, Humans, Male, Middle Aged, Propafenone, Prospective Studies, Self Administration, Stroke Volume
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