Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach

N Engl J Med. 2004 Dec 2;351(23):2384-91. doi: 10.1056/NEJMoa041233.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Ambulatory Care
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Feasibility Studies
  • Female
  • Flecainide / administration & dosage
  • Flecainide / adverse effects
  • Flecainide / therapeutic use*
  • Follow-Up Studies
  • Heart Failure / complications*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Propafenone / administration & dosage
  • Propafenone / adverse effects
  • Propafenone / therapeutic use*
  • Prospective Studies
  • Self Administration
  • Stroke Volume


  • Anti-Arrhythmia Agents
  • Propafenone
  • Flecainide