Skip to main content
SpringerLink
Log in

New antiarrhythmic drugs for atrial fibrillation: Focus on dronedarone and vernakalant

  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

The prevalence of atrial fibrillation (AF) is forecast to rise to 2–5% of the general population by 2050. Of the two fundamental treatment strategies for AF management, rhythm control is the approach which is generally preferred for active, symptomatic, and/or younger patients, whereas rate control is all that is found necessary in the more elderly, sedentary, asymptomatic individual. In many cases, at neither extreme, there remains a genuine choice of therapy, and for those patients, antiarrhythmic strategies would be preferred if effective and safe antiarrhythmic medications were available. Many new antiarrhythmic agents exploiting new mechanisms of action or novel combinations of established antiarrhythmic activity are currently being investigated. Agents which selectively inhibit ion channels specifically involved in atrial repolarization, so-called atrial repolarization delaying agents, are widely acknowledged as potentially ideal antiarrhythmic treatments, as they will probably be both effective and safe, at the very least (free of pro-arrhythmic effects at the ventricular level). Modified analogues of traditional antiarrhythmic drugs with different combinations of ion channel and receptor blocking effects, novel mechanisms of action, and less complicated metabolic profiles are also under development. Completely innovative antiarrhythmic agents with new antiarrhythmic mechanisms, such as stretch receptor antagonism, sodium calcium exchanger blockade, late sodium channel inhibition, and gap junction modulation are also being explored. In addition, there is increasing evidence in support of the antiarrhythmic action of non-antiarrhythmic drugs. Treatments with statins, omega-3 fatty acids, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and aldosterone antagonists are all potentially valuable, over and above any effect related to the treatment of underlying heart disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Camm, A. J., Savelieva, I., & Lip, G. Y. (2007). Rate control in the medical management of atrial fibrillation. Heart, 93, 35–38.

    Article  PubMed  CAS  Google Scholar 

  2. Jahangiri, M., Weir, G., Mandal, K., Savelieva, I., & Camm, J. (2006). Current strategies in the management of atrial fibrillation. Annals of Thoracic Surgery, 82, 357–364.

    Article  PubMed  Google Scholar 

  3. Savelieva, I., & Camm, J. (2008). Update on atrial fibrillation: Part II. Clinical Cardiology, 31, 102–108.

    Article  PubMed  Google Scholar 

  4. Touboul, P., Brugada, J., Capucci, A., Crijns, H. J., Edvardsson, N., & Hohnloser, S. H. (2003). Dronedarone for prevention of atrial fibrillation: a dose-ranging study. European Heart Journal, 24, 1481–1487.

    Article  PubMed  CAS  Google Scholar 

  5. Singh, B. N., Connolly, S. J., Crijns, H. J., Roy, D., Kowey, P. R., Capucci, A., et al. (2007). Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. New England Journal of Medicine, 357, 987–999.

    Article  PubMed  CAS  Google Scholar 

  6. Hohnloser, S. H., & Singh, B. N. (2005). Dronedarone significantly decrease the combined endpoint of hospitalization and death in patients with atrial fibrillation. Circulation, 112(Supplement II), 325–326.

    Google Scholar 

  7. Gautier, P., Serre, M., Cosnier-Pucheu, S., Djandjighian, L., Roccon, A., Herbert, J. M., et al. (2005). In vivo and in vitro antiarrhythmic effects of SSR149744C in animal models of atrial fibrillation and ventricular arrhythmias. Journal of Cardiovascular Pharmacology, 45, 125–135.

    Article  PubMed  CAS  Google Scholar 

  8. Kowey, P. R., Aliot, E. M., Capucci, A., Connolly, S. J., Crijns, H. J., Hohnloser, S. H., et al. (2007). Placebo-controlled double-blind dose-ranging study of the efficacy and safety of SSR149744C in patients with recent atrial fibrillation/flutter. Heart Rhythm, 4(Supplement 5S), S72 (abstract).

    Google Scholar 

  9. Kowey, P., Eliot, E. M., Capucci, A., Connolly, S. J, Crijns, H., Hohnloser, S. H., et al. (2008). Placebo-controlled double-blind dose-ranging study of the efficacy and safety of celivarone for the prevention of ventricular arrhythmia-triggered ICD interventions. Journal of the American College of Cardiology, 51(Supplement A2), (abstract).

  10. Pritchett, E. L., Page, R. L., Connolly, S. J., Marcello, S. R., Schnell, D. J., & Wilkinson, W. E. (2000). Antiarrhythmic effects of azimilide in atrial fibrillation: Efficacy and dose–response. Journal of the American College of Cardiology, 36, 794–802.

    Article  PubMed  CAS  Google Scholar 

  11. Camm, A. J., Pratt, C. M., Schwartz, P. J., Al-Khalidi, H. R., Spyt, M. J., Holroyde, M. J., et al. (2004). Mortality in patients with recent myocardial infarction: A randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification. Circulation, 109, 990–996.

    Article  PubMed  Google Scholar 

  12. Pratt, C. M., Singh, S. N., Al-Khalidi, H. R., Brum, J. M., Holroyde, M. J., Marcello, S. R., et al. (2004). The efficacy of azimilide in the treatment of atrial fibrillation in the presence of left ventricular systolic dysfunction: Results from the Azimilide Postinfarct Survival Evaluation (ALIVE) trial. Journal of the American College of Cardiology, 43, 1211–1216.

    Article  PubMed  CAS  Google Scholar 

  13. Pritchett, E. L., Kowey, P., Connolly, S., Page, R. L., Kerr, C., Wilkinson, W. E., et al. (2006). Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. American Heart Journal, 151, 1043–1049.

    Article  PubMed  CAS  Google Scholar 

  14. Lombardi, F., Borggrefe, M., Ruzyllo, W., Luderitz, B., & A-COMET-II Investigators (2006). Azimilide vs placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial. European Heart Journal, 27, 2224–2231.

    Article  PubMed  CAS  Google Scholar 

  15. Kerr, C. R., Connolly, S. J., Kowey, P., Page, R. L., Pritchett, E. L., Ruda, M. Y., et al. (2006). Efficacy of azimilide for the maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation in the presence and absence of structural heart disease. American Journal of Cardiology, 98, 215–218.

    Article  PubMed  CAS  Google Scholar 

  16. Hohnloser, S. H., Dorian, P., Straub, M., Beckmann, K., & Kowey, P. (2004). Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter. Journal of the American College of Cardiology, 44, 99–104.

    Article  PubMed  CAS  Google Scholar 

  17. Roy, D., Rowe, B. H., Stiell, I. G., Coutu, B., Ip, J. H., Phaneuf, D., et al. (2004). A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation. Journal of the American College of Cardiology, 44, 2355–2361.

    Article  PubMed  CAS  Google Scholar 

  18. Roy, D., Pratt, C. M., Torp-Pedersen, C., Wyse, D. G., Toft, E., Juul-Moller, S., et al. (2008). Vernakalant hydrochloride for rapid conversion of atrial fibrillation: A phase 3, randomized, placebo-controlled trial. Circulation, 117, 1518–1525.

    Article  PubMed  CAS  Google Scholar 

  19. Roy, D., Pratt, C., Juul-Møller, S., Toft, E., Wyse, D. G., Nielsen, T., et al. (2006). Efficacy and tolerance of RSD1235 in the treatment of atrial fibrillation or atrial flutter: Results of a phase III, randomized, placebo-controlled, multicenter trial. Journal of the American College of Cardiology, 47(Supplement A), 10A (abstract).

    Google Scholar 

  20. CARDIOME PHARMA CORP. Retrieved February 29, 2008 from http://www.cardiome.com/VernakalantOral.php.

  21. Pharmaceutical BUSINESS Review. Retrieved April 12, 2008 from http://www.pharmaceutical-business-review.com/article_news.asp?guid=CF004A79-C1D8-45E3-A431-B29EE1B34D41.

  22. Rivard, L., Shiroshita-Takeshita, A., Maltais, C., Ford, J., Pinnock, R., Madge, D., et al. (2005). Electrophysiological and atrial antiarrhythmic effects of a novel I Kur/Kv1.5 blocker in dogs. Heart Rhythm, 2(Supplement 1S), S180 (abstract).

    Article  Google Scholar 

  23. Polontchouk, L., Haefliger, J. A., Ebelt, B., Schaefer, T., Stuhlmann, D., Mehlhorn, U., et al. (2001). Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria. Journal of the American College of Cardiology, 38, 883–891.

    Article  PubMed  CAS  Google Scholar 

  24. Wetzel, U., Boldt, A., Lauschke, J., Weigl, J., Schirdewahn, P., Dorszewski, A., et al. (2005). Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies. Heart, 91, 166–170.

    Article  PubMed  CAS  Google Scholar 

  25. Shiroshita-Takeshita, A., Sakabe, M., Haugan, K., Hennan, J. K., & Nattel, S. (2007). Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs. Circulation, 115, 310–318.

    Article  PubMed  CAS  Google Scholar 

  26. Bode, F., Sachs, F., & Franz, M. R. (2001). Tarantula peptide inhibits atrial fibrillation. Nature, 409, 35–36.

    Article  PubMed  CAS  Google Scholar 

  27. Burashnikov, A., Di Diego, J. M., Zygmunt, A. C., Belardinelli, L., & Antzelevitch, C. (2007). Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: Differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation, 116, 1449–1457.

    Article  PubMed  CAS  Google Scholar 

  28. Savelieva, I., & Camm, A. J. (2004). Atrial fibrillation and heart failure: Natural history and pharmacological treatment. Europace, 5(Supplement 1), S5–S19.

    Article  PubMed  Google Scholar 

  29. Lee, K. W., Everett, T. H., Rahmutula, D., Guerra, J. M., Wilson, E., Ding, C., et al. (2006). Pirfenidone prevents the development of a vulnerable substrate for atrial fibrillation in a canine model of heart failure. Circulation, 114, 1703–1712.

    Article  PubMed  CAS  Google Scholar 

  30. Dernellis, J., & Panaretou, M. (2004). Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. European Heart Journal, 25, 1100–1117.

    Article  PubMed  CAS  Google Scholar 

  31. Jahangiri, M., & Camm, A. J. (2007). Do corticosteroids prevent atrial fibrillation after cardiac surgery. Nature Clinical Practice Cardiovascular Medicine, 4, 592–593.

    Article  PubMed  Google Scholar 

  32. Savelieva, I., & Camm, J. (2008). Statins and polyunsaturated fatty acids for treatment of atrial fibrillation. Nature Clinical Practice Cardiovascular Medicine, 5, 30–41.

    Article  PubMed  CAS  Google Scholar 

  33. Patti, G., Chello, M., Candura, D., Pasceri, V., D’Ambrosio, A., Covino, E., et al. (2006). Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) Study. Circulation, 114, 1455–1461.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiac & Vascular Sciences, St George’s University of London, Cranmer Terrace, London, SW17 0RE, UK

    A. John Camm & Irina Savelieva

Authors
  1. A. John Camm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irina Savelieva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. John Camm.

Additional information

Professor A. John Camm is a consultant to AstraZeneca, Cardiome, sanofi aventis, and Xention.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Camm, A.J., Savelieva, I. New antiarrhythmic drugs for atrial fibrillation: Focus on dronedarone and vernakalant. J Interv Card Electrophysiol 23, 7–14 (2008). https://doi.org/10.1007/s10840-008-9269-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-008-9269-3

Keywords

Search

Navigation