Do we need pharmacological therapy for atrial fibrillation in the ablation era?

  • Samuel Lévy


Management of atrial fibrillation (AF) remains one of the most difficult problems of modern cardiology. Pharmacological antiarrhythmic therapy is used both for termination of episodes of AF and for prevention of AF recurrences. Recently, major trials have compared the strategy of maintenance of sinus rhythm, called rhythm control, with the strategy of heart rate control during AF and found that the rhythm control strategy was not superior to rate control in terms of mortality. Although subsequent analysis identified rhythm control as a factor of improved survival, these large trials have markedly influenced the management of AF. One of the hypotheses explaining the non-superiority of the rhythm control strategy was that the benefit of sinus rhythm was offset by the side effects of antiarrhythmic agents. As a consequence, attention was directed to non-pharmacological therapies, particularly to catheter ablation of the trigger or/and the atrial substrate using radiofrequency current or cryothermia. However, despite the reported good results of various types of interventions in the hands of highly qualified teams, catheter ablation cannot be applied to all patients with AF or to all types of AF. Furthermore, catheter ablation of AF requires sophisticated electrophysiologic laboratories equipped with expensive imaging techniques and a well-trained staff that cannot be available in sufficient number to cover the growing epidemic of AF with acceptable efficacy and safety even in rich countries. Therefore, there is still a need for pharmacological therapy aimed at the prevention of AF recurrences for the majority of AF patients. So far, attempts to provide the physician with efficient antiarrhythmic agents having a good safety profile have not been successful. However, recent research resulted in promising new approaches including prevention of AF using converting enzyme inhibitors or angiotensin 2 receptor blockers, new antiarrhythmic agents with multichannel effects such as dronedarone and tedisamil and atrial specific agents that theoretically should have no ventricular proarrhythmic effect as they target specific atrial channels such as IKAch and IKur which are absent at the ventricular level. Other possible mechanisms of AF that represent potential targets, such as modification of stretch-activated ion channels, intervention of altered connexin expression and altered gap-junctional conductance, are currently investigated.


Atrial fibrillation Ablation Pharmacological therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lévy, S., Breithardt, G., Campbell, R. W., Camm, A. J., Daubert, J. C., Allessie, M., et al. (1998). Atrial fibrillation: Current knowledge and recommendations for management. Working Group on Arrhythmias of the European Society of Cardiology. European Heart Journal, 19, 1294–1320.PubMedCrossRefGoogle Scholar
  2. 2.
    Lévy, S., Camm, A. J., Saksena, S., Aliot, E., Breithardt, G., Crijns, H., et al. (2003). International consensus on nomenclature and classification of atrial fibrillation. Europace, 5, 119–122.PubMedCrossRefGoogle Scholar
  3. 3.
    Fuster, V., Ryden, L., Asinger, R. W., Cannom, D. S., Crijns, H. J., Frye, R. L., et al. (2001). 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 for Practice Guidelines and Policy Conferences. European Heart Journal, 22, 1852–1923.PubMedCrossRefGoogle Scholar
  4. 4.
    Wyse, D. G., for the AFFIRM Investigators (2002). Survival in patients presenting with atrial fibrillation: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. New England Journal of Medicine, 347, 1825–1833.PubMedCrossRefGoogle Scholar
  5. 5.
    Van Gelder, I. C., Hagens, V. E., Bosker, H. A., Kingma, J. H., Kamp, O., Kingma, T., et al. (2002). A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. New England Journal of Medicine, 347, 1834–1840.PubMedCrossRefGoogle Scholar
  6. 6.
    Haissaguerre, M., Jais, P., Shah, D. C., Takahashi, A., Hocini, M., Quiniou, G., et al. (1998). Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. New England Journal of Medicine, 339, 659–666.PubMedCrossRefGoogle Scholar
  7. 7.
    Oral, H., Chugh, A., Good, E., Sankaran, S., Reich, S. S., Igic, P., et al. (2006). A tailored approach to catheter ablation of paroxysmal atrial fibrillation. Circulation, 18(113), 1824–1831.CrossRefGoogle Scholar
  8. 8.
    Karch, M. R., Zrenner, B., Deisenhofer, I., Schreieck, J., Ndrepepa, G., Dong, J., et al. (2005). Freedom from atrial tachyarrhythmias after catheter ablation of atrial fibrillation: A randomized comparison between 2 current ablation strategies. Circulation, 7(111), 2875–2880.CrossRefGoogle Scholar
  9. 9.
    Pappone, C., & Santinelli, V. (2005). Atrial fibrillation ablation: State of the art. American Journal of Cardiology, 96(12A), 59L–64L.PubMedCrossRefGoogle Scholar
  10. 10.
    Wood, M. A., & Ellenbogen, K. A. (2006). Catheter ablation of chronic atrial fibrillation—The gap between promise and practice. New England Journal of Medicine, 354, 967–969.PubMedCrossRefGoogle Scholar
  11. 11.
    Lévy, S., Maarek, M., Coumel, P., Guize, L., Lekieffre, J., Medvedowsky, J. L., et al. (1999). Characterization of different subsets of atrial fibrillation in general practice in France: The Alfa study. Circulation, 99, 3028–3035.PubMedGoogle Scholar
  12. 12.
    Vaughan Williams, E. M. (1984). A classification of antiarrhythmic actions reassessed after a decade of new drugs. Journal of Clinical Pharmacology, 24, 129–147.PubMedGoogle Scholar
  13. 13.
    Steinberg, J. S., Sadaniantz, A., Kron, J., Krahn, A., Denny, D. M., Daubert, J., et al. (2004). Analysis of cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Circulation, 27(109), 1973–1980.CrossRefGoogle Scholar
  14. 14.
    Patten, M., Maas, R., Bauer, P., Lüderitz, B., Sonntag, F., Dluzniewski, M., et al. (2004). Suppression of paroxysmal atrial tachyarrhythmias—Results of the SOPAT trial. European Heart Journal, 25, 1395–1404.PubMedCrossRefGoogle Scholar
  15. 15.
    Roy, D., Talajic, M., Dorian, P., Connolly, S., Eisenberg, M. J., Green, M., et al. (2000). Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. New England Journal of Medicine, 342, 913–920.PubMedCrossRefGoogle Scholar
  16. 16.
    Singh, B. N., Singh, S. N., Reda, D. J., Tang, X. C., Lopez, B., Harris, C. L., et al. (2005). Amiodarone versus sotalol for atrial fibrillation. New England Journal of Medicine, 352, 1861.PubMedCrossRefGoogle Scholar
  17. 17.
    Fuster, V., Ryden, L. E., Cannom, D. S., Crijns, H. J., Curtis, A. B., Ellenbogen, K. A., et al. (2006). 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. Journal of the American College of Cardiology, 48, e149–e246 (Aug 15).CrossRefGoogle Scholar
  18. 18.
    Santini, M., De Ferrari, G. M., Pandozi, C., et al. (2004). Atrial fibrillation requiring urgent medical care. Approach and outcome in the various departments of admission. Data from atrial fibrillation/flutter Italian Registry Trial (FIRE). Italian Heart Journal, 5, 205–213.PubMedGoogle Scholar
  19. 19.
    Capucci, A., Tizziano, L., Boriani, G., Trisolino, G., Binetti, N., Cavazza, M., et al. (1992). Effectiveness of loading oral flecainide for converting recent–onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. American Journal of Cardiology, 70, 69–72.PubMedCrossRefGoogle Scholar
  20. 20.
    Alboni, P., Botto, G. L., Baldi, N., Luzi, M., Russo, V., Gianfranchi, L., et al. (2004). Outpatient treatment of recent–onset atrial fibrillation with the “pill-in-the-pocket” approach. New England Journal of Medicine, 351, 2384–2391.PubMedCrossRefGoogle Scholar
  21. 21.
    Stambler, B. S., Wood, M. A., Ellenbogen, K. A., Perry, K. T., Wakefield, L. K., & VanderLugt, J. T. (1996). Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation, 1(94), 1613–1621.Google Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    Pritchett, E. L., Kowey, P., Connolly, S., Page, R. L., Kerr, C., & Wilkinson, W. E. (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.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    Kathofer, S., Thomas, D., & Karle, C. A. (2005). The novel antiarrhythmic drug dronedarone: Comparison with amiodarone. Cardiovascular Drug Reviews, 23, 217–230.PubMedCrossRefGoogle Scholar
  27. 27.
    Levy, S. (2006). Drug insight: Angiotensin-converting-enzyme inhibitors and atrial fibrillation—Indications and contraindications. Nat Clin Pract Cardiovascular Med, 3(4), 220–225.CrossRefGoogle Scholar
  28. 28.
    Klein, H. U., & Goette, A. (2003). Blockade of atrial angiotensin II type 1 receptors: A novel antiarrhythmic strategy to prevent atrial fibrillation? Journal of the American College of Cardiology, 41, 2197–2204.CrossRefGoogle Scholar
  29. 29.
    Pedersen, O. D., Bagger, H., Kober, L., & Torp-Pedersen, C. (1999). Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation, 100, 376–380.PubMedGoogle Scholar
  30. 30.
    Li, D., Shinagawa, K., Pang, L., Leung, T. K., Cardin, S., Wang, Z., et al. (2001). Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation, 104, 2608–2616.PubMedGoogle Scholar
  31. 31.
    Nattel, S., & Li, D. (2000). Ionic remodelling in the heart: Pathophysiological significance and new therapeutic opportunities for atrial fibrillation. Circulation Research, 87, 440–447.PubMedGoogle Scholar
  32. 32.
    Madrid, A. H., Bueno, M. G., Rebollo, J. M. G., Marin, I., Pena, G., Bernal, E., et al. (2002). Use of Irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. Circulation, 106, 331–336.PubMedCrossRefGoogle Scholar
  33. 33.
    Madrid, A. H., Peng, J., Zamora, J., Marin, I., Bernal, E., Escobar, C., et al. (2004). The role of angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors in the prevention of atrial fibrillation in patients with cardiovascular diseases: Meta-analysis of randomized controlled clinical trials. PACE, 27, 1405–1410.PubMedGoogle Scholar
  34. 34.
    Goldstein, R. N., Khrestian, C., Carlsson, L., & Waldo, A. L. (2004). Azd7009: A new antiarrhythmic drug with predominant effects on the atria effectively terminates and prevents reinduction of atrial fibrillation and flutter in the sterile pericarditis model. Journal of Cardiovascular Electrophysiology, 1444–1450.Google Scholar
  35. 35.
    Persson, F., Carlsson, L., Duker, G., & Jacobson, I. (2005). Blocking characteristics of hERG, hNav1.5, and hKvLQT1/hminK after administration of the novel anti-arrhythmic compound AZD7009. Journal of Cardiovascular Electrophysiology, 16(3), 329–341.PubMedCrossRefGoogle Scholar
  36. 36.
    Blaauw, Y., Gogelein, H., Tieleman, R. G., van Hunnik, A., Schotten, U., & Allessie, M. A. (2004). “Early” class III drugs for the treatment of atrial fibrillation: Efficacy and atrial selectivity of AVE0118 in remodeled atria of the goat. Circulation, 110, 1717–1724.PubMedCrossRefGoogle Scholar
  37. 37.
    Roy, D., Rowe, B. H., Stiell, I. G., Coutu, B., Ip, J. H., Phaneuf, D., et al. CRAFT Investigators (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.PubMedCrossRefGoogle Scholar
  38. 38.
    Gilmour, R. F., & Zipes, D. P. (2004). Mechanisms of disease: New mechanisms of antiarrhythmic actions. Natural Clinical Practice. Cardiovascular Medicine, 1, 37–41.Google Scholar
  39. 39.
    Satoh, T., & Zipes, D. P. (1996). Unequal atrial stretch in dogs increases dispersion of refractoriness conducive to developing atrial fibrillation. Journal of Cardiovascular Electrophysiology, 7, 833−842.PubMedGoogle Scholar
  40. 40.
    Bode, F., Sachs, F., & Franz, M. R. (2001). Tarantula peptide inhibits atrial fibrillation. Nature, 409, 35−36.PubMedCrossRefGoogle Scholar
  41. 41.
    Yao, J.-A., Hussain, W., Patel, P., Peters, N. S., Boyden, P. A., Wit, A. L., et al. (2003). Remodeling of gap junction channel function in epicardial border zone of healing canine infarcts. Circulation Research, 92, 437−443.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Service de CardiologieHôpital NordMarseillesFrance

Personalised recommendations