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The incidence and predictors of overall adverse effects caused by low dose amiodarone in real-world clinical practice

  • Kim, Hack-Lyoung (Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine) ;
  • Seo, Jae-Bin (Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine) ;
  • Chung, Woo-Young (Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine) ;
  • Kim, Sang-Hyun (Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine) ;
  • Kim, Myung-A (Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine) ;
  • Zo, Joo-Hee (Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine)
  • Received : 2013.08.27
  • Accepted : 2014.04.07
  • Published : 2014.09.01

Abstract

Background/Aims: Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size. Methods: Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response. Results: The mean daily dose of amiodarone was $227{\pm}126mg$, and the mean duration was $490{\pm}812days$. During the mean follow-up duration of $982{\pm}1,137days$, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year). Conclusions: Low-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.

Keywords

References

  1. Haffajee CI, Love JC, Alpert JS, Asdourian GK, Sloan KC. Efficacy and safety of long-term amiodarone in treatment of cardiac arrhythmias: dosage experience. Am Heart J 1983;106(4 Pt 2):935-943. https://doi.org/10.1016/0002-8703(83)90019-4
  2. Nademanee K, Singh BN, Hendrickson J, et al. Amiodarone in refractory life-threatening ventricular arrhythmias. Ann Intern Med 1983;98(5 Pt 1):577-584. https://doi.org/10.7326/0003-4819-98-5-577
  3. Parra O, Ruiz J, Ojanguren I, Navas JJ, Morera J. Amiodarone toxicity: recurrence of interstitial pneumonitis after withdrawal of the drug. Eur Respir J 1989;2:905-907.
  4. Kang HM, Kang YS, Kim SH, et al. Amiodarone-induced hepatitis and polyneuropathy. Korean J Intern Med 2007;22:225-229. https://doi.org/10.3904/kjim.2007.22.3.225
  5. Tavares AB, Paula SK, Vaisman M, Teixeira Pde F. Amiodarone and thyrotoxicosis: case reports. Arq Bras Cardiol 2010; 95:e122-e124. https://doi.org/10.1590/S0066-782X2010001500022
  6. Kwon KH, Jeong SW, Uh S, et al. A case of amiodarone-associated pulmonary toxicity. Korean J Intern Med 1995;10:155-159. https://doi.org/10.3346/jkms.1995.10.3.155
  7. Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol 1997;30:791-798. https://doi.org/10.1016/S0735-1097(97)00220-9
  8. Roy D, Talajic M, Dorian P, et al. Amiodarone to prevent recurrence of atrial fibrillation: Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000;342:913-920. https://doi.org/10.1056/NEJM200003303421302
  9. Piccini JP, Berger JS, O'Connor CM. Amiodarone for the prevention of sudden cardiac death: a meta-analysis of randomized controlled trials. Eur Heart J 2009;30:1245-1253. https://doi.org/10.1093/eurheartj/ehp100
  10. Julian DG, Camm AJ, Frangin G, et al. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 1997;349:667-674. https://doi.org/10.1016/S0140-6736(96)09145-3
  11. 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. https://doi.org/10.1056/NEJMoa043399
  12. AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003;42:20-29. https://doi.org/10.1016/S0735-1097(03)00559-X
  13. Amiodarone Trials Meta-Analysis Investigators. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Lancet 1997;350:1417-1424. https://doi.org/10.1016/S0140-6736(97)05281-1
  14. Nallamothu BK, Hayward RA, Bates ER. Beyond the randomized clinical trial: the role of effectiveness studies in evaluating cardiovascular therapies. Circulation 2008;118:1294-1303. https://doi.org/10.1161/CIRCULATIONAHA.107.703579
  15. Jackevicius CA, Tom A, Essebag V, et al. Population-level incidence and risk factors for pulmonary toxicity associated with amiodarone. Am J Cardiol 2011;108:705-710. https://doi.org/10.1016/j.amjcard.2011.04.024
  16. Goldschlager N, Epstein AE, Naccarelli G, Olshansky B, Singh B. Practical guidelines for clinicians who treat patients with amiodarone: Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med 2000;160:1741-1748. https://doi.org/10.1001/archinte.160.12.1741
  17. Santangeli P, Di Biase L, Burkhardt JD, et al. Examining the safety of amiodarone. Expert Opin Drug Saf 2012;11:191-214. https://doi.org/10.1517/14740338.2012.660915
  18. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med 2005;118:706-714. https://doi.org/10.1016/j.amjmed.2004.11.028
  19. Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev 2001; 22:240-254.
  20. Babatin M, Lee SS, Pollak PT. Amiodarone hepatotoxicity. Curr Vasc Pharmacol 2008;6:228-236. https://doi.org/10.2174/157016108784912019
  21. Podrid PJ. Amiodarone: reevaluation of an old drug. Ann Intern Med 1995;122:689-700. https://doi.org/10.7326/0003-4819-122-9-199505010-00008
  22. Lewis JH, Ranard RC, Caruso A, et al. Amiodarone hepatotoxicity: prevalence and clinicopathologic correlations among 104 patients. Hepatology 1989;9:679-685. https://doi.org/10.1002/hep.1840090504
  23. Mantyjarvi M, Tuppurainen K, Ikaheimo K. Ocular side effects of amiodarone. Surv Ophthalmol 1998;42:360-366. https://doi.org/10.1016/S0039-6257(97)00118-5
  24. Camus P, Martin WJ 2nd, Rosenow EC 3rd. Amiodarone pulmonary toxicity. Clin Chest Med 2004;25:65-75. https://doi.org/10.1016/S0272-5231(03)00144-8
  25. Ernawati DK, Stafford L, Hughes JD. Amiodarone-induced pulmonary toxicity. Br J Clin Pharmacol 2008;66:82-87. https://doi.org/10.1111/j.1365-2125.2008.03177.x
  26. Oyama N, Oyama N, Yokoshiki H, et al. Detection of amiodarone-induced pulmonary toxicity in supine and prone positions: high-resolution computed tomography study. Circ J 2005;69:466-470. https://doi.org/10.1253/circj.69.466
  27. Weinberg BA, Miles WM, Klein LS, et al. Five-year follow- up of 589 patients treated with amiodarone. Am Heart J 1993;125:109-120. https://doi.org/10.1016/0002-8703(93)90063-F
  28. Yamada Y, Shiga T, Matsuda N, Hagiwara N, Kasanuki H. Incidence and predictors of pulmonary toxicity in Japanese patients receiving low-dose amiodarone. Circ J 2007;71:1610-1616. https://doi.org/10.1253/circj.71.1610

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