New antiarrhythmic drugs for atrial fibrillation: Focus on dronedarone and vernakalant
- 215 Downloads
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.
KeywordsAtrial fibrillation Antiarrhythmic drugs Rhythm control Atrial repolarization delaying agents Dronedarone Vernakalant Gap junction modifiers Rotigaptide
- 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.PubMedCrossRefGoogle 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).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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.
- 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar