Arrhythmias are a major cause of morbidity and mortality, and atrial fibrillation is the most widespread disorder of cardiac rhythm. Amiodarone is an effective antiarrhythmic agent that has been in clinical use for about 20 years. It is effective for multiple types of arrhythmias, including atrial fibrillation, and has a low incidence of cardiac adverse events, including Torsade de Pointes. It has many noncardiac adverse effects that are serious and limit its long-term use. Dronedarone is an investigational antiarrhythmic agent that is designed to have similar cardiac effects to amiodarone but with fewer adverse effects. This review presents some of the animal and human studies that evaluate the effects of dronedarone.
Kodama I., Kamiya K., Toyama J.Cellular electropharmacology of amiodarone. Cardiovasc Res . 1997;35:13-29.
2.
Doggrell SAAmiodarone: waxed and waned and waxed again. Expert OpinPharmacother. 2001;2:1877-1890.
3.
Camm J.Pharmacologic management of atrial fibrillation: where do we currently stand ? Medscape Cardiol.2005;9:2.
4.
Vorperian VR , Havighurst TC, Miller S., et al. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol.1997;30:791-798.
5.
Braunwald E. ShattuckLecture: cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med.1997;337:1360-1369.
6.
Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults. JAMA.2001 ;285: 2370-2375.
7.
Tsang Tsm, Gersh BJAtrial fibrillation: an old disease, a new epidemic. Am J Med, 2002;113:432-435.
8.
Wolf PA, Abbott RD, Kannel WBAtrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke. 1991;22:983—988.
9.
Benjamin EJ, Wolf, PA, D'Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham heart study. Circulation.1998;98:946-952.
10.
Stewart S., Hart CL, Hole DJ, et al. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med.2002;113:359-364.
11.
Feinberg WM, Blackshear JL, Laupacis A., et al. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med.1995;155:469-473.
12.
Singh BNAtrial fibrillation: epidemiologic considerations and rationale for conversion and maintenance of sinus rhythm. J Cardiovasc Pharmacol Therapeut . 2003;8:S13-S26.
13.
AFFIRM Investigators.A Comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med.2002;347:1825-1833.
14.
Vidaillet HJRate control vs. rhythm control in the management of atrial fibrillation in elderly persons. Am J Geriatr Cardiol.2005;14:73-78.
15.
Hancox JC, Patel Kcr, Jones JVAntiarrhythmics— from cell to clinic: past, present, and future. Heart. 2000;84:14-24.
16.
Nattel S.Atrial electrophysiology and mechanism of atrial fibrillation. J Cardiovasc Pharmacol Therapeut. 2003;8:S5-S11.
17.
Singh BN, Sarma Jsm.Mechanisms of action of antiarrhythmic drugs relative to the origin and perpetuation of cardiac arrhythmias. J Cardiovasc Pharmacol Therapeut. 2001;6:69-87.
18.
Lee K., Park JY, Ryu PD, Kwon LS, Kim HYIKr channel blockers: novel antiarrhythmic agents. Curr Med Chem Cardiovasc Hematol Agents.2003 ; 1:203-223.
19.
Elming H., Brendorp B., Pehrnos S., Pedersen OD, Kober L., Torp-Petersen C.A benefit-risk assessment of class III antiarrhythmic agents. Expert OpinDrug Saf.2004; 3:559-577.
20.
Lombardi F. , Terranova P.Pharmacological treatment of atrial fibrillation: mechanisms of action and efficacy of class III drugs. Curr Med Chem. 2006;13:1635-1653.
21.
Sun W., Sarma Jsm, Singh BNElectrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart: comparison with amiodarone. Circulation.1999;100:2276-2281.
22.
Sun W., Sarma Jsm, Singh BNChronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: comparison with amiodarone. J Cardiovasc Pharmacol.2002;39:677-684.
23.
Varro A., Takacs J., Nemeth M., et al. Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone. Br J Pharmacol.2001;133:625-634.
24.
Gautier P., Guillemare E., Marion A., et al. Electrophysiologic characterization of dronedarone in guinea pig ventricular cells. J Cardiovasc Pharmacol.2003;41:191-202.
25.
van Opstal JM , Schoenmakers M., Verduyn SC et al. Chronic amiodarone evokes no torsade de pointes arrhythmias despite QT lengthening in an animal model of acquired long-QT syndrome. Circulation. 2001;104: 2722-2727.
26.
Chatelain P. , Meysmans L., Matteazzi JR, et al. Interaction of the antiarrhythmic agents SR 33589 and amiodarone with the beta-adrenoceptor and adenylate cyclase in rat heart. Br J Pharmacol.1995;116:1949-1956.
27.
Hodeige D., HeyndrickxJ-P, Chatelain P, Manning A. SR 33589, a new amiodarone-like antiarrhythmic agent: anti-adrenoceptor activity in anaesthetized and conscious dogs. Eur J Pharmacol.1995;279:25-32.
28.
Lalevee N., Barrere-Lemaire S., Gautier P., et al. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol . 2003; 14:885-890.
29.
Snyders D.Structure and function of cardiac potassium channels. Cardiovasc Res.1999;42:377-390.
30.
Deal KK, England SK, Tamkun MMMolecular physiology of cardiac potassium channels. Physiol Rev.1996;76:49-67.
31.
Tamargo J., Caballero R., Gomez R., et al. Pharmacology of cardiac potassium channels. Cardiovasc Res. 2004; 62:9-33.
32.
Ridley JM, Milnes JT, Witchel, HJ, Hancox, JC. High affinity HERG K+ channel blockade by the antiarrhythmic agent dronedarone: resistance to mutations of the S6 residues Y652 and F656 . Biochem Biophys Res Commun.2004;325:883-891.
33.
Aimond F., Beck L., Gautier P., et al. Cellular and in vivo electrophysiological effects of dronedarone in normal and postmyocardial infarcted rats. J Pharmacol Exp Ther.2000;292:415-424.
34.
Watanabe Y. , Hara, Y., Tamagawa M., Nakaya, H.Inhibitory effect of amiodarone on the muscarinic acetylcholine receptor-operated potassium current in guinea pig atrial cells . J Pharmacol Exp Ther.1996;279:617-624.
35.
Altomare C. , Barbuti A., Viscomi C., et al. Effects of dronedarone on acetylcholine-activated current in rabbit SAN cells. Br J Pharmacol.2000;130:1315-1320.
36.
Guillemare E., Marion A., Nisato D., Gautier P.Inhibitory effects of dronedarone on muscarinic K+ current in guinea pig atrial cells. J Cardiovasc Pharmacol.2000;36:802-805.
37.
Kathofer S. , Thomas D., Karle C.The novel antiarrhythmic drug dronedarone: comparison with amiodarone. Cardiovasc Drug Rev. 2005;23:217-230.
38.
Hynes BJ, Luck JC, Wolbrette DL, et al. A review of the pharmacokinetics, electrophysiology and clinical safety of dronedarone. Future Cardiol.2005 ;1:135-144.
39.
Touboul P., Brugada J., Capucci A., et al. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur Heart J.2003;24:1481-1487.
40.
Schellekens S., Verheugh Fwa.Hotline sessions of the 26th European congress of cardiology. Eur Heart J.2004;25:2164-2166.
41.
Hohnloser SH, Klinikum Der.Dronedarone significantly decreases the combined endpoint of hospitalization and death in patients with atrial fibrillation. American Heart Associations Scientific Sessions2005, poster 1637. http://aha.scientificposters.com/postersearch.cfm .
42.
Davy J.Dronedarone demonstrates additional rate control on top of standard pharmacotherapies in the treatment of atrial fibrillation. American Heart Associations Scientific Sessions2005, poster 2737. Available at: http://aha.scientificposters.com/postersearch.cfm .
43.
Pantos C., Mourouzis, I., Malliploulou V., et al. Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor α1. Thyroid. 2005;15:16-23.
44.
van Beeren HC, Jong, Wmc, Kaptein E., et al. Dronedarone acts as a selective inhibitor of 3,5,3 α-triiodothyronine binding to thyroid hormone receptorα1: in vitro and in vivo evidence. Endocrinology.2003; 144:552-558.
45.
Quaglino D. , Ha HR, Duner E., et al. Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship. Am J Physiol Lung Cell Mol Physiol. 2004;287:L438-L447.
46.
Tschuppert Y., Buclin T., Rothuizen LE, et al. Effect of dronedarone on renal function in healthy subjects. Clin Pharmacol Ther.2005;2:P10,PI-9.
