Adverse effects of low dose amiodarone: a meta-analysis
VR Vorperian,
TC Havighurst,
S Miller,
and
CT January
Department of Medicine, University of Wisconsin School of Medicine, Madison, USA. vrv@medicine.wisc.edu
OBJECTIVES: We sought to assess the odds of experiencing adverse effects with low dose amiodarone therapy compared with placebo. BACKGROUND: An estimate of the likelihood of experiencing amiodarone-related adverse effects with exposure to low daily doses of the drug is lacking in the published reports, and little information is available on adverse effect event rates in control groups not receiving the drug. METHODS: Data from four published trials involving 1,465 patients were included in a meta-analysis design. The criteria for inclusion were 1) double-blind, placebo-controlled design; 2) absence of a crossover design between patient groups; 3) mean follow-up of at least 12 months; 4) maintenance amiodarone dose < or = 400 mg/day; and 5) presence of an explicit description of adverse effects. Data were pooled after testing for homogeneity of treatment effects across trials, and summary odds ratios were calculated by the Peto-modified Mantel-Haenszel method for each adverse effect. RESULTS: The mean amiodarone dose per day ranged from 152 to 330 mg; 738 patients were randomized to receive amiodarone and 727 placebo. Exposure to amiodarone in this dose range, for a minimal duration of 12 months, resulted in odds similar to those of placebo for hepatic and gastrointestinal adverse effects, but in significantly higher odds than those of placebo (p < 0.05) for experiencing thyroid (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.0 to 8.7), neurologic (OR 2.0, 95% CI 1.1 to 3.7), skin (OR 2.5, 95% CI 1.1 to 6.2), ocular (OR 3.4, 95% CI 1.2 to 9.6) and bradycardic (OR 2.2, 95% CI 1.1 to 4.3) adverse effects. A trend toward increased odds of pulmonary toxicity was noted (OR 2.0, 95% CI 0.9 to 5.3), but this did not reach statistical significance (p = 0.07). The unadjusted total incidence of drug discontinuation was 22.9% in the amiodarone group and 15.4% in the placebo group. The odds of discontinuing the drug in the amiodarone group was approximately 1.5 times that of the placebo group (OR 1.52, 95% CI 1.2 to 1.9) (p = 0.003). CONCLUSIONS: Compared with placebo, there is a higher likelihood of experiencing several amiodarone-related adverse effects with exposure to low daily doses of the drug. Thus, although low dose amiodarone may be well tolerated, it is not free of adverse effects.
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|
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|
 
T. R Betts
Is rate more important than rhythm in treating atrial fibrillation? Yes
BMJ,
August 21, 2009;
339(aug21_1):
b3173 - b3173.
[Full Text]
|
|
|
|
|
|
|
C. F. Orr and J. E. Ahlskog
Frequency, Characteristics, and Risk Factors for Amiodarone Neurotoxicity
Arch Neurol,
July 1, 2009;
66(7):
865 - 869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Willis and A. M. Lugo
Amiodarone-induced neurotoxicity
Am. J. Health Syst. Pharm.,
March 15, 2009;
66(6):
567 - 569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Kamp
Drug-Induced Lung Diseases
ACCP Pulmonary Med Brd Rev,
January 1, 2009;
25(0):
319 - 344.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ahmed, M. Rienstra, H. J. G. M. Crijns, T. P. Links, A. C. P. Wiesfeld, H. L. Hillege, H. A. Bosker, D. J. A. Lok, D. J. Van Veldhuisen, I. C. Van Gelder, et al.
Continuous vs Episodic Prophylactic Treatment With Amiodarone for the Prevention of Atrial Fibrillation: A Randomized Trial
JAMA,
October 15, 2008;
300(15):
1784 - 1792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Kober, C. Torp-Pedersen, J. J.V. McMurray, O. Gotzsche, S. Levy, H. Crijns, J. Amlie, J. Carlsen, and the Dronedarone Study Group
Increased Mortality after Dronedarone Therapy for Severe Heart Failure
N. Engl. J. Med.,
June 19, 2008;
358(25):
2678 - 2687.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Vassallo and R. G. Trohman
Prescribing Amiodarone: An Evidence-Based Review of Clinical Indications
JAMA,
September 19, 2007;
298(11):
1312 - 1322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Essebag, M. R. Reynolds, T. Hadjis, R. Lemery, B. Olshansky, A. E. Buxton, M. E. Josephson, and P. Zimetbaum
Sex Differences in the Relationship Between Amiodarone Use and the Need for Permanent Pacing in Patients With Atrial Fibrillation
Arch Intern Med,
August 13, 2007;
167(15):
1648 - 1653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Conen, L. Melly, C. Kaufmann, S. Bilz, P. Ammann, B. Schaer, C. Sticherling, B. Muller, and S. Osswald
Amiodarone-Induced Thyrotoxicosis: Clinical Course and Predictors of Outcome
J. Am. Coll. Cardiol.,
June 19, 2007;
49(24):
2350 - 2355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tafreshi and J. Rowles
A Review of the Investigational Antiarrhythmic Agent Dronedarone
Journal of Cardiovascular Pharmacology and Therapeutics,
March 1, 2007;
12(1):
15 - 26.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. M. Bagshaw, P. D. Galbraith, L. B. Mitchell, R. Sauve, D. V. Exner, and W. A. Ghali
Prophylactic Amiodarone for Prevention of Atrial Fibrillation After Cardiac Surgery: A Meta-Analysis
Ann. Thorac. Surg.,
November 1, 2006;
82(5):
1927 - 1937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al.
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Europace,
September 1, 2006;
8(9):
651 - 745.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
J. Am. Coll. Cardiol.,
August 15, 2006;
48(4):
e149 - e246.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society
Circulation,
August 15, 2006;
114(7):
e257 - e354.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G Karthikeyan
The value of rhythm control in mitral stenosis.
Heart,
August 1, 2006;
92(8):
1013 - 1016.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gulizia, S. Mangiameli, G. Chiaranda, V. Spadola, N. Di Giovanni, A. Colletti, V. Bulla, A. Circo, O. Pensabene, L. Vasquez, et al.
Design and rationale of a randomized study to compare amiodarone and Class IC anti-arrhythmic drugs in terms of atrial fibrillation treatment efficacy in patients paced for sinus node disease: the PITAGORA trial.
Europace,
April 1, 2006;
8(4):
302 - 305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Rubinstein, P. J. Zimetbaum, M. E. Josephson, A. Schlegel, K. R. Desai, B. N. Singh, S. N. Singh, and D. Reda
Amiodarone versus sotalol for atrial fibrillation.
N. Engl. J. Med.,
August 11, 2005;
353(6):
627 - 630.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. Falk
Rate Control Is Preferable to Rhythm Control in the Majority of Patients With Atrial Fibrillation
Circulation,
June 14, 2005;
111(23):
3141 - 3150.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Bokhari, D. Newman, M. Greene, V. Korley, I. Mangat, and P. Dorian
Long-Term Comparison of the Implantable Cardioverter Defibrillator Versus Amiodarone: Eleven-Year Follow-Up of a Subset of Patients in the Canadian Implantable Defibrillator Study (CIDS)
Circulation,
July 13, 2004;
110(2):
112 - 116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Channer, A. Birchall, R. P. Steeds, S. J. Walters, W. W. Yeo, J. N. West, R. Muthusamy, W. E. Rhoden, B. T. Saeed, P. Batin, et al.
A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation
Eur. Heart J.,
January 2, 2004;
25(2):
144 - 150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Touboul, J. Brugada, A. Capucci, H. J.G.M. Crijns, N. Edvardsson, and S. H. Hohnloser
Dronedarone for prevention of atrial fibrillation: A dose-ranging study
Eur. Heart J.,
August 2, 2003;
24(16):
1481 - 1487.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Lee, L. D. Green, P. P. Liu, P. Dorian, D. M. Newman, F. C. Grant, J. V. Tu, and D. A. Alter
Effectiveness of implantable defibrillators for preventing arrhythmic events and death: A Meta-Analysis
J. Am. Coll. Cardiol.,
May 7, 2003;
41(9):
1573 - 1582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Letelier, K. Udol, J. Ena, B. Weaver, and G. H. Guyatt
Effectiveness of Amiodarone for Conversion of Atrial Fibrillation to Sinus Rhythm: A Meta-analysis
Arch Intern Med,
April 14, 2003;
163(7):
777 - 785.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Ott, A. Khoor, J. P. Leventhal, T. E. Paterick, and C. D. Burger
Pulmonary Toxicity in Patients Receiving Low-Dose Amiodarone
Chest,
February 1, 2003;
123(2):
646 - 651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Krahn, G. Klein, A.C. Skanes, and R. Yee
Amiodarone: pearl or peril?
Eur. Heart J.,
July 1, 2002;
23(13):
1001 - 1002.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.B Lumer, D Roy, M Talajic, A Couturier, J Lambert, N Frasure-Smith, B Thibault, M Dubuc, P Gagne, and S Nattel
Amiodarone reduces procedures and costs related to atrial fibrillation in a controlled clinical trial
Eur. Heart J.,
July 1, 2002;
23(13):
1050 - 1056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. B. Schron, D. V. Exner, Q. Yao, L. S. Jenkins, J. S. Steinberg, J. R. Cook, S. P. Kutalek, P. L. Friedman, R. S. Bubien, R. L. Page, et al.
Quality of Life in the Antiarrhythmics Versus Implantable Defibrillators Trial: Impact of Therapy and Influence of Adverse Symptoms and Defibrillator Shocks
Circulation,
February 5, 2002;
105(5):
589 - 594.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. van Opstal, M. Schoenmakers, S. C. Verduyn, S.H. M. de Groot, J. D.M. Leunissen, F. F. van der Hulst, M. M.C. Molenschot, H. J.J. Wellens, and M. A. Vos
Chronic Amiodarone Evokes No Torsade de Pointes Arrhythmias Despite QT Lengthening in an Animal Model of Acquired Long-QT Syndrome
Circulation,
November 27, 2001;
104(22):
2722 - 2727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S M Cobbe, R W F Campbell, A J Camm, A W Nathan, E Rowland, P E Bloch-Thomsen, M Moller, and L Jordaens
Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia
Heart,
November 1, 2001;
86(5):
522 - 526.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology
Eur. Heart J.,
October 2, 2001;
22(20):
1852 - 1923.
[PDF]
|
|
|
|
|
|
|
V. Fuster, L. E. Ryden, R. W. Asinger, D. S. Cannom, H. J. Crijns, R. L. Frye, J. L. Halperin, G. N. Kay, W. W. Klein, S. Levy, et al.
ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology
J. Am. Coll. Cardiol.,
October 1, 2001;
38(4):
1266 - 1266.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. P. Raatikainen, T. E. Morey, P. Druzgala, P. Milner, M. D. Gonzalez, and D. M. Dennis
Potent and Reversible Effects of ATI-2001 on Atrial and Atrioventricular Nodal Electrophysiological Properties in Guinea Pig Isolated Perfused Heart
J. Pharmacol. Exp. Ther.,
November 1, 2000;
295(2):
779 - 785.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. Aggarwal, E. M. Furmaga, C. B. Good, M. Talajic, D. Roy, and J. Lambert
Amiodarone to Prevent Recurrence of Atrial Fibrillation
N. Engl. J. Med.,
August 24, 2000;
343(8):
578 - 580.
[Full Text]
|
|
|
|
|
|
|
N. Goldschlager, A. E. Epstein, G. Naccarelli, B. Olshansky, B. Singh, and for the Practice Guidelines Subcommittee, North Am
Practical Guidelines for Clinicians Who Treat Patients With Amiodarone
Arch Intern Med,
June 26, 2000;
160(12):
1741 - 1748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. Vardas, G. E. Kochiadakis, N. E. Igoumenidis, A. M. Tsatsakis, E. N. Simantirakis, and G. I. Chlouverakis
Amiodarone as a First-Choice Drug for Restoring Sinus Rhythm in Patients With Atrial Fibrillation : A Randomized, Controlled Study
Chest,
June 1, 2000;
117(6):
1538 - 1545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Roy, M. Talajic, P. Dorian, S. Connolly, M. J. Eisenberg, M. Green, T. Kus, J. Lambert, M. Dubuc, P. Gagne, et al.
Amiodarone to Prevent Recurrence of Atrial Fibrillation
N. Engl. J. Med.,
March 30, 2000;
342(13):
913 - 920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-C. Loh
Current concepts in medicine: Amiodarone-induced thyroid disorders: a clinical review
Postgrad. Med. J.,
March 1, 2000;
76(893):
133 - 140.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
W. Sun, J. S. M. Sarma, and B. N. Singh
Electrophysiological Effects of Dronedarone (SR33589), a Noniodinated Benzofuran Derivative, in the Rabbit Heart : Comparison With Amiodarone
Circulation,
November 30, 1999;
100(22):
2276 - 2281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Odeh, E. Schiff, and A. Oliven
Hyponatremia During Therapy With Amiodarone
Arch Intern Med,
November 22, 1999;
159(21):
2599 - 2600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Torp-Pedersen, M. Moller, P. E. Bloch-Thomsen, L. Kober, E. Sandoe, K. Egstrup, E. Agner, J. Carlsen, J. Videbak, B. Marchant, et al.
Dofetilide in Patients with Congestive Heart Failure and Left Ventricular Dysfunction
N. Engl. J. Med.,
September 16, 1999;
341(12):
857 - 865.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Catherwood, W. D. Fitzpatrick, M. L. Greenberg, P. T. Holzberger, D. J. Malenka, B. R. Gerling, and J. D. Birkmeyer
Cost-Effectiveness of Cardioversion and Antiarrhythmic Therapy in Nonvalvular Atrial Fibrillation
Ann Intern Med,
April 20, 1999;
130(8):
625 - 636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
HOW SAFE IS LOW-DOSE AMIODARONE?
Journal Watch (General),
September 5, 1997;
1997(905):
7 - 7.
[Full Text]
|
|
|
|
