Correspondence
Amiodarone for Atrial Fibrillation
N Engl J Med 2007; 356:2424-2426June 7, 2007
- Article
To the Editor:
In his review article on amiodarone for atrial fibrillation, Zimetbaum (March 1 issue)1 did not mention that there are two forms of amiodarone-induced thyrotoxicosis (AIT) — an important distinction that has a major influence on subsequent management. In type I AIT, patients usually have preexisting thyroid abnormalities, such as nodular goiter, an autonomous thyroid nodule, or latent Graves' disease. This syndrome is thought to be due to the Jod–Basedow phenomenon. In type II AIT, the thyroid gland is normal, and thyrotoxicosis results from subacute destructive thyroiditis with the release of preformed thyroid hormone. The uptake of radioactive iodine is normal or high in type I AIT but low or absent in type II AIT. Moreover, parenchymal blood flow as seen on color-flow Doppler is present in type I AIT but absent in type II AIT.2 The treatment of type I AIT involves thionamides, potassium perchlorate, or lithium and discontinuation of amiodarone, whereas the treatment of type II AIT involves glucocorticoids.3
3 ReferencesHabib ur Rehman, F.R.C.P.C.
Regina Qu'Appelle Health Region, Regina, SK S4P 3X15, Canada
habib31@sasktel.net 1
Zimetbaum P . Amiodarone for atrial fibrillation. N Engl J Med 2007;356:935-941
Full Text | Web of Science | Medline2
Loh K-C . Amiodarone-induced thyroid disorders: a clinical review. Postgrad Med J 2000;76:133-140
CrossRef | Web of Science | Medline3
Newman CM ,Price A ,Davies DW ,Gray TA ,Weetman AP . Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy. Heart 1998;79:121-127
Web of Science | Medline
To the Editor:
Zimetbaum discusses the difficulties in recognizing the onset of AIT, which is often associated with only mild clinical signs and symptoms. Many patients receiving amiodarone are also treated with warfarin. Thyroid function affects the pharmacodynamics of warfarin: hyperthyroidism potentiates the anticoagulant effect of warfarin, whereas hypothyroidism attenuates the anticoagulant effect.1 Therefore, an otherwise unexplained rise in the international normalized ratio in such patients can be a valuable clue to the onset of AIT even before the manifestation of other clinical symptoms2 and should prompt laboratory assessment of thyroid function.
2 ReferencesDaniel Kurnik, M.D.
Vanderbilt University Medical School, Nashville, TN 37232
daniel.kurnik@vanderbilt. edu Ronen Loebstein, M.D.
David Olchovsky, M.D.
Chaim Sheba Medical Center, 52621 Tel Hashomer, Israel1
Demirkan K ,Stephens MA ,Newman KP ,Self TH . Response to warfarin and other oral anticoagulants: effects of disease states. South Med J 2000;93:448-454
Web of Science | Medline2
Kurnik D ,Loebstein R ,Farfel Z ,Ezra D ,Halkin H ,Olchovsky D . Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Medicine (Baltimore) 2004;83:107-113
CrossRef | Web of Science | Medline
To the Editor:
Zimetbaum reports that “amiodarone is an excellent choice for use in patients with structural heart disease or congestive heart failure.” However, the cited Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT)1 enrolled a small population, lasted only 2 years, and lacked an on-treatment analysis despite its significant dropout rate.
The sum of these factors undermines the value of the asserted neutral effect of amiodarone on mortality. Furthermore, the recent Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)2 showed no difference in outcome according to the cause of disease, negating the concept from CHF-STAT that amiodarone is potentially beneficial in nonischemic congestive heart failure; the study also revealed a worrisome reduction in survival among patients in New York Heart Association class III. Cause for concern also arose from the Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA),3 in which dronedarone, an iodine-free amiodarone derivative, was associated with an increase in mortality in a population with a reduced ejection fraction. Several mechanisms through which amiodarone may have an adverse effect on the course of congestive heart failure have been described.4 After consideration of all these facts, it would be prudent to recommend against amiodarone therapy when atrial fibrillation coexists with congestive heart failure.
4 ReferencesMichele Coceani, M.D.
Institute of Clinical Physiology, 56124 Pisa, Italy
michecoc@ifc.cnr. it 1
Singh SN ,Fletcher RD ,Fisher SG , et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. N Engl J Med 1995;333:77-82
Full Text | Web of Science | Medline2
Bardy GH ,Lee KL ,Mark DB , et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237[Erratum, N Engl J Med 2005;352:2146.]
Full Text | Web of Science | Medline3
Sanofi-Aventis U.S. Merrill Lynch Global Pharmaceutical Conference, September 24, 2003. (Accessed May 17, 2007, at http://www.sanofi-aventis.com/Images/20030924_Merrill_Lynch_fr_tcm23-7753.pdf.)
4
Coceani M ,Mariotti R . Is amiodarone safe in heart failure? BMJ 2006;332:317-318
CrossRef | Web of Science | Medline
To the Editor:
Zimetbaum leaves out an important piece of data for deciding whether antiarrhythmic therapy should be recommended for a patient with atrial fibrillation — data on mortality. The results of the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T),1 which showed a decrease in recurrence of atrial fibrillation in the antiarrhythmic-therapy groups as compared with placebo, also showed that patients who received the study drug had a mortality ratio of 2.0 (P=0.11 for the comparison of amiodarone and placebo). An increase in mortality has been remarkably consistent in numerous studies, none of which have been powered to look at mortality. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial2 enrolled 4060 patients and at 5 years showed a hazard ratio for mortality of 1.15 (P=0.08) for treatment with antiarrhythmic drugs. The Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) trial3 randomly assigned 522 patients with atrial fibrillation to receive either antiarrhythmic therapy or rate control and showed more primary end points, including deaths, in the group undergoing antiarrhythmic therapy. The information on mortality from numerous studies is important to consider as a consistent and troubling signal.
3 ReferencesNeil Skolnik, M.D.
Abington Memorial Hospital, Abington, PA 190461
Singh BN ,Singh SN ,Reda DJ , et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861-1872
Full Text | Web of Science | Medline2
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators
Full Text | Web of Science | Medline3
Van Gelder IC ,Hagens VE ,Bosker HA , et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834-1840
Full Text | Web of Science | Medline
To the Editor:
Zimetbaum states that neurologic side effects may occur in up to 30% of patients receiving amiodarone therapy and may be more common in the elderly. Treatment-emergent parkinsonism has been reported with amiodarone use1,2 but is underrecognized and difficult to treat. The drug's half-life is long and variable, averaging 58 days.3 Consequently, if parkinsonism is recognized late, several months may elapse before reversal can be expected. Moreover, I have encountered an instance in which use of amiodarone in a patient with preexisting Parkinson's disease was associated with aggravation of muscular rigidity. This previously ambulatory patient became frozen and virtually immobile within 2 months after the initiation of treatment with amiodarone. Since his family could no longer care for him, he had to be moved to a nursing home. Explicit enumeration of parkinsonism among the treatment-emergent neurologic side effects of amiodarone may promote an earlier recognition of this condition. Use of amiodarone is probably inadvisable in patients with preexisting Parkinson's disease.
3 ReferencesCarmel Armon, M.D., M.H.S.
Baystate Medical Center, Springfield, MA 01199
carmel.armon@bhs. org 1
Werner EG ,Olanow CW . Parkinsonism and amiodarone therapy. Ann Neurol 1989;25:630-632
CrossRef | Web of Science | Medline2
Dotti MT ,Federico A . Amiodarone-induced parkinsonism: a case report and pathogenetic discussion. Mov Disord 1995;10:233-234
CrossRef | Web of Science | Medline3
Siddoway LA . Amiodarone: guidelines for use and monitoring. Am Fam Physician 2003;68:2189-2198
Web of Science | Medline
Author/Editor Response
Rehman and Kurnik et al. raise important issues related to amiodarone and its interaction with the thyroid. Mention of these issues was omitted from my article owing to word constraints, but the correspondents' discussion of these interactions is very welcome.
Coceani and Skolnik both raise appropriate concerns about the safety and possible increase in mortality associated with the use of amiodarone, particularly among patients with congestive heart failure. It is quite clear from numerous studies they mention that amiodarone does not reduce the rate of death from all causes or from arrhythmia in any population, particularly in patients with congestive heart failure. There may be a trend toward increased mortality in this latter population, but it has not been shown to be significant. Furthermore, implantable cardioverter–defibrillators are increasingly used in this population, which potentially limits the adverse cardiovascular outcomes associated with amiodarone (e.g., bradycardia and torsades de pointes). I believe there are insufficient data and justification to accept Coceani's recommendation that amiodarone should be avoided in patients with atrial fibrillation and congestive heart failure.
Armon mentions the potential for exacerbation of parkinsonism associated with amiodarone. This phenomenon is infrequent and has been described in case reports only; however, it is worrisome and clearly warrants a more systematic evaluation.
Peter Zimetbaum, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215
pzimetba@bidmc.harvard. edu - Citing Articles (1)
Citing Articles
1
J. F. Doyle, K. M. Ho. (2009) Benefits and Risks of Long-term Amiodarone Therapy for Persistent Atrial Fibrillation: A Meta-analysis. Mayo Clinic Proceedings 84:3, 234-242
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