Correspondence
The “Pill-in-the-Pocket” Approach to Atrial Fibrillation
N Engl J Med 2005; 352:1150-1151March 17, 2005
- Article
To the Editor:
Alboni and colleagues (Dec. 2 issue)1 present data from a prospective study investigating the strategy of rhythm control in patients with paroxysmal atrial fibrillation by self-administration of antiarrhythmic agents (the “pill-in-the-pocket” approach). According to the inclusion criteria, patients 18 to 75 years old were recruited, with 44 percent of the study population having some structural heart disease. Therefore, some of these patients were likely to have had risk factors for stroke and should have received antithrombotic therapy, which is considered a cornerstone of treatment for atrial fibrillation.2-4 Accordingly, the authors should provide additional information on the short-term and long-term anticoagulation regimens and on the outcome with regard to transient ischemia, stroke, or arterial embolism in their patients.
4 ReferencesGerian C. Grönefeld, M.D.
Stefan H. Hohnloser, M.D.
Klinikum der J.W. Goethe Universität, 60590 Frankfurt, Germany
groenefeld@em.uni-frankfurt. de 1
Alboni P ,Botto GL ,Baldi N , et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket“ approach. N Engl J Med 2004;351:2384-2391
Full Text | Web of Science | Medline2
Fuster V ,Ryden LE ,Asinger RW , et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. Circulation 2001;104:2118-2150
Web of Science | Medline3
Singer DE ,Albers GW ,Dalen JE ,Go AS ,Halperin JL ,Manning WJ . Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:Suppl 3:429S-456S
CrossRef | Web of Science | Medline4
Rockson SG ,Albers GW . Comparing the guidelines: anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation. J Am Coll Cardiol 2004;43:929-935
CrossRef | Web of Science | Medline
To the Editor:
The pill-in-the-pocket approach proposed by Alboni et al., which involves the administration of a single dose of propafenone or flecainide to treat paroxysmal atrial fibrillation, should be applied and interpreted with great caution. We have several concerns — the population was highly selected and small, there was no comparative control or other treatment group, and there were inconsistent drug and dosing schedules.
Atrioventricular nodal blocking drugs are associated with a 68 percent rate of conversion of atrial fibrillation with a recent onset (i.e., within 48 hours).1 Augmenting this percentage and shortening the time to conversion may not be worth the risk, especially if patients have undetected heart disease and are at risk for the development of an adverse response to propafenone or flecainide.2
We are further troubled because many patients with symptomatic atrial fibrillation often have asymptomatic episodes3 and often at an alarmingly high rate.4 Advocating self-administration of antiarrhythmic drugs for such patients may predispose them to thromboembolic events. Although we agree with Alboni et al. that the pill-in-the-pocket approach may be useful, we suggest caution in selecting patients for this approach.
4 ReferencesSuma H. Konety, M.D.
Brian Olshansky, M.D.
University of Iowa Hospitals and Clinics, Iowa City, IA 52242
brian-olshansky@uiowa.edu 1
Danias PG ,Caulfield TA ,Weigner MJ ,Silverman DI ,Manning WJ . Likelihood of spontaneous conversion of atrial fibrillation to sinus rhythm. J Am Coll Cardiol 1998;31:588-592
CrossRef | Web of Science | Medline2
The Cardiac Arrhythmia Suppression Trial (CAST) Investigators
Full Text | Web of Science | Medline3
Page RL ,Tilsch TW ,Connolly SJ , et al. Asymptomatic or “silent“ atrial fibrillation: frequency in untreated patients and patients receiving azimilide. Circulation 2003;107:1141-1145
CrossRef | Web of Science | Medline4
Page RL ,Wilkinson WE ,Clair WK ,McCarthy EA ,Pritchett EL . Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation 1994;89:224-227
Web of Science | Medline
To the Editor:
The widespread adoption of the pill-in-the-pocket strategy for the management of paroxysmal atrial fibrillation could lead to clinically significant interactions with two oral medications commonly used in the management of atrial fibrillation. Propafenone is a potent inhibitor of the metabolism of warfarin,1 which is used for stroke prevention in the majority of patients with atrial fibrillation, and also reduces the nonrenal clearance of digoxin,2 which is often used for rate control.
Clinically significant drug interactions are most likely to occur when interacting drugs are added or discontinued or used on an as-needed basis, as is suggested in this study. Transient overanticoagulation could develop in patients who take concurrent warfarin, leading to an increased risk of hemorrhagic complications. Similarly, the interaction of propafenone and digoxin could lead to toxic effects of digoxin. Patients in whom propafenone is prescribed in this manner should be counseled about the risks and clinical presentation of these and other potential drug interactions.
2 ReferencesAnn K. Wittkowsky, Pharm.D.
University of Washington School of Pharmacy, Seattle, WA 98195
akwitt@u.washington. edu 1
Kates RE ,Yee YG ,Kirsten EB . Interaction between warfarin and propafenone in healthy volunteer subjects. Clin Pharmacol Ther 1987;42:305-311
CrossRef | Web of Science | Medline2
Nolan PE Jr ,Marcus FI ,Erstad BL ,Hoyer GL ,Furman C ,Kirsten EB . Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects. J Clin Pharmacol 1989;29:46-52
Web of Science | Medline
Author/Editor Response
Drs. Grönefeld and Hohnloser request information on antithrombotic treatment. In our study protocol, anticoagulation was not standardized but was left to the local practice of each center. Fifteen patients (7 percent) were treated with warfarin, and 38 (18 percent) with aspirin. During the follow-up period, no patient had a transient ischemic attack, stroke, or arterial embolism. However, we believe that the indications for antithrombotic therapy are not clearly defined in patients with transient, symptomatic episodes of atrial fibrillation that are treated with either the pill-in-the-pocket approach or long-term oral prophylaxis; this point deserves further investigation.
Drs. Konety and Olshansky underscore the lack of a control group. In many studies carried out in hospitalized patients, oral flecainide or propafenone has been shown to be superior to placebo in rapidly terminating atrial fibrillation of recent onset. In our opinion, further study to demonstrate this superiority was not indicated. We agree with Drs. Konety and Olshansky that the pill-in-the-pocket approach should be used only in selected patients. Current data show that flecainide and propafenone are safe in patients without heart disease or with only mild heart disease; thus, the exclusion criteria we used should be strictly adopted in clinical practice. We enrolled highly symptomatic patients with palpitations, who contacted the emergency room for almost all the arrhythmic episodes, as shown in Table 1 of our article. About one third of emergency room visits were followed by hospitalization. Emergency room visits and hospitalizations often represent the most important concern for patients with recurrent atrial fibrillation. Not only did the pill-in-the-pocket approach make the arrhythmic episodes shorter, but it also dramatically reduced emergency room visits and hospitalizations. Although these patients were highly symptomatic with palpitations, we cannot rule out asymptomatic arrhythmic episodes in some of them. However, this would not represent a specific finding of the pill-in-the-pocket approach, since asymptomatic episodes have been observed during all antiarrhythmic treatments (long-term oral prophylaxis, catheter ablation, and pacemaker implantation).1-3
Dr. Wittkowsky raises the problem of drug interactions. In particular, she refers to the interactions of propafenone with digitalis or warfarin. In our study, no patient was taking digitalis. The data on the interactions between propafenone and warfarin apply to long-term treatment with both drugs.4 Moreover, we are not aware of any clinical study reporting more hemorrhagic complications in patients receiving oral propafenone than in those receiving other antiarrhythmic agents.
4 ReferencesPaolo Alboni, M.D.
Ospedale Civile, 44042 Cento, Italy
p.alboni@ausl. fe. it Giovanni I. Botto, M.D.
Ospedale S. Anna, 22100 Como, ItalyNicola Baldi, M.D.
Ospedale SS. Annunziata, 74100 Taranto, Italy1
Page RL ,Tilsch TW ,Connolly SJ , et al. Asymptomatic or “silent“ atrial fibrillation: frequency in untreated patients and patients receiving azimilide. Circulation 2003;107:1141-1145
CrossRef | Web of Science | Medline2
Oral H ,Veerareddy S ,Good E , et al. Prevalence of asymptomatic recurrences of atrial fibrillation after successful radiofrequency catheter ablation. J Cardiovasc Electrophysiol 2004;15:920-924
CrossRef | Web of Science | Medline3
Israel CW ,Gronefeld G ,Ehrlich JR ,Li YG ,Hohnloser SH . Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. J Am Coll Cardiol 2004;43:47-52
CrossRef | Web of Science | Medline4
Kates RE ,Yee YG ,Kirsten EB . Interaction between warfarin and propafenone in healthy volunteer subjects. Clin Pharmacol Ther 1987;42:305-311
CrossRef | Web of Science | Medline
- Citing Articles (4)
Citing Articles
1
Rakesh Gopinathannair, Renee M. Sullivan, Brian Olshansky. (2009) Update on medical management of atrial fibrillation in the modern era. Heart Rhythm 6:8, S17-S22
CrossRef2
Mark E. Anderson. (2006) Too Little, Too Late: Chasing Atrial Fibrillation with Sodium Channel Antagonists. Journal of Cardiovascular Electrophysiology 17:6, 655-656
CrossRef3
TETSUO KATO. (2006) Nihon Naika Gakkai Zasshi 95:5, 821-825
CrossRef4
Brian Olshansky. (2005) Rate versus rhythm control strategies for AF. Current Treatment Options in Cardiovascular Medicine 7:5, 371-381
CrossRef
