Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 141 No. 0910 (2011)

Dronedarone for the management of atrial fibrillation

  • Roman Brenner
  • Etienne Delacrétaz
DOI
https://doi.org/10.4414/smw.2011.13158
Cite this as:
Swiss Med Wkly. 2011;141:w13158
Published
28.02.2011

Summary

Atrial fibrillation is a common arrhythmia associated with increased cardiovascular mortality and morbidity including stroke, heart failure and hospitalisations. Major studies on atrial fibrillation have shown no significant difference between rhythm and rate control in terms of mortality. However, rate control treatment may be insufficient to prevent morbidity in a number of patients. Amiodarone is generally considered the agent with the best efficacy for maintaining normal sinus rhythm. Despite amiodarone’s efficacy, its use is often limited by its side effect profile and it is not currently recommended as the first choice antiarrhythmic agent, except in patients with heart failure or congenital heart disease. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been recently approved by Swissmedic for management of patients with atrial fibrillation or atrial flutter. Structural modification of dronedarone was introduced to decrease lipophilicity, shorten the half-life and minimise non-cardiovascular toxicity as compared to amiodarone. This article reviews the pharmacology, adverse effects and clinical evidence available to date on the use of dronedarone in the management of atrial fibrillation.

References

  1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8.
  2. Flegel KM, Shipley MJ, Rose G. Risk of stroke in non-rheumatic atrial fibrillation. Lancet. 1987;1(8532):526–9.
  3. Conen D, Osswald S, Albert CM. Epidemiology of atrial fibrillation. Swiss Med Wkly. 2009;139(25–26):346–52.
  4. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946–52.
  5. Stewart S, Hart CL, Hole DJ, McMurray JJ. 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(5):359–64.
  6. Sun W, Sarma JS, Singh BN. Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart: comparison with amiodarone. Circulation. 1999;100(22):2276–81.
  7. Gautier P, Guillemare E, Marion A, Bertrand JP, Tourneur Y, Nisato D. Electrophysiologic characterization of dronedarone in guinea pig ventricular cells. J Cardiovasc Pharmacol. 2003;41(2):191–202.
  8. Touboul P, Brugada J, Capucci A, Crijns HJ, Edvardsson N, Hohnloser SH. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur Heart J. 2003;24(16):1481–7.
  9. Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987–99.
  10. Davy JM, Herold M, Hoglund C, Timmermans A, Alings A, Radzik D, et al. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial fibrillation (ERATO) study. Am Heart J. 2008;156(3):527 e1–9.
  11. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825–33.
  12. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004;109(12):1509–13.
  13. Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668–78.
  14. Page R, Connolly S, Crijns H, Eickels M, Gaudin C, Torp-Petersen C, et al. Abstract 4097: Rhythm- and Rate-Controlling Effects of Dronedarone in Patients with Atrial Fibrillation: Insights From the ATHENA Trial. Circulation. 2008;118: p. S_827.
  15. Connolly SJ, Crijns HJ, Torp-Pedersen C, van Eickels M, Gaudin C, Page RL, et al. Analysis of stroke in ATHENA: a placebo-controlled, double-blind, parallel-arm trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter. Circulation. 2009;120(13):1174–80.
  16. Kober L, Torp-Pedersen C, McMurray JJ, Gotzsche O, Levy S, Crijns H, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358(25):678–87.
  17. Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, et al. Dronedarone in patients with congestive heart failure: insights from ATHENA. Eur Heart J. 2010;31(14):1717–21.
  18. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J.
  19. Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol. 21(6):597–605.
  20. Piccini JP, Hasselblad V, Peterson ED, Washam JB, Califf RM, Kong DF. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. J Am Coll Cardiol. 2009;54(12):1089–95.
  21. Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol. 2010;21(6):597–605.
  22. Tschuppert Y, Buclin T, Rothuizen LE, Decosterd LA, Galleyrand J, Gaud C, et al. Effect of dronedarone on renal function in healthy subjects. Br J Clin Pharmacol. 2007;64(6):785–91.
  23. Shirolkar SC, Fiuzat M, Becker RC. Dronedarone and vitamin K antagonists: a review of drug-drug interactions. Am Heart J. 160(4):577–82.
  24. http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4417b1-02-Sanofi_Aventis.pdf. last access dec 14 2010.
  25. Damy T, Pousset F, Caplain H, Hulot JS, Lechat, P. Pharmacokinetic and pharmacodynamic interactions between metoprolol and dronedarone in extensive and poor CYP2D6 metabolizer healthy subjects. Fundam Clin Pharmacol. 2004;18(1):113–23.
  26. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369–429.
  27. Jouven X, Desnos M, Guerot C, Ducimetiere P. Idiopathic atrial fibrillation as a risk factor for mortality. The Paris Prospective Study I. Eur Heart J. 1999;20(12):896–9.
  28. Dries DL, Exner DV, Gersh BJ, Domanski MJ, Waclawiw MA, Stevenson LW. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32(3):695–703.

Most read articles by the same author(s)