What is vernakalant and what is its place in clinical practice?

Česká verzia

Authors: J. Murín; J. Vítovec
Authors place of work: I. interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně ; I. interna klinika, Univerzitná nemocnica Bratislava
Published in the journal: Kardiol Rev Int Med 2012, 14(2): 115-119
Category: Reports from Foreign countries

Summary

Pharmacological cardioversion is a frequent approach used by doctors with respect to atrial fibrillation in routine clinical practice. It ensures the modification (version) of arrhythmia to the sinus rhythm or contributes to the control and suppression of symptoms of the disease (usually palpitation, breathlessness, weakness, anxiety). In this treatment, proven antiarrhythmics are used which, however, are frequently not so effective or are effective after a longer period (hours, days). Even today, clinical practice requires new antiarrhythmics – especially those with a fast effect, both effective and safe, effective in treating atrial fibrillation and without a (negative) impact on the electrical activity of the ventricles. Vernakalant is one of these new “atrial selective” antiarrhythmics. It is administered intravenously and has been approved for use in the European Union. The article presents its pharmacological characteristics, its effectiveness and safety (based on available clinical trials).

Keywords:
atrial fibrillation – medicamentous cardioversion – selective atrial antiarrhythmics – vernakalant

Zdroje

1. Go AS, Hylek EM, Phillips KA et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. JAMA 2001; 285: 2370–2375.

2. Steg PG, Alam S, Chiang CE et al. RealiseAF investigators. Symptoms, functional status and quality of life in patients with controlled and uncontrolled atrial fibrillation: data from the RealiseAF cross-sectional international registry. Heart Online, published on September 22, 2011 as 10.1136/heartjnl-2011-300550.

3. Kannel WB, Wolf PA, Benjamin EJ et al. Prevalence, incidence prognosis and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998; 82: 2N–9N.

4. Lloyd-Jones DM, Wang TJ, Leip EP et al. Life-time risk for development of atrial fibrillation: the Framingham heart study. Circulation 2004; 110: 1042–1046.

5. Wyse DG, Waldo AL, Di Marco JP et al. Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825–1833.

6. Roy D, Talajic M, Nattel S et al. Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008; 358: 2667–2677.

7. Galagher MM, Yap YG, Padula M et al. Arrhythmic complications of electrical cardioversion: relationship to shock energy. Int J Cardiol 2008; 123: 307–312.

8. Nichol G, McAlister F, Pham B et al. Meta-analysis of randomised controlled trials of the effectiveness of antiarrhythmic agents at promoting sinus rhythm in patients with atrial fibrillation. Heart 2002; 87: 535–543.

9. Dobrev D, Nattel S. New antiarrhythmic drugs for treatment of atrial fibrillation. Lancet 2010; 375: 1212–1223.

10. Camm AJ, Savelieva I. New antiarrhythmic drugs for atrial fibrillation: focus on dronedarone and vernakalant. J Interv Card Electrophysiol 2008; 23: 7–14.

11. Fedida D, Orth PM, Chen JY et al. The mechanism of atrial antiarrhythmic action of RSD 1235. J Cardiovasc Electrophysiol 2005; 16: 1227–1238.

12. Amos GJ, Wettwer E, Metzger F et al. Differences between outward currents of human atrial and subepicardial ventricular myocytes. J Physiol (Lond.) 1996; 491: 31–50.

13. Dobrev D, Friedrich A, Voigt N et al. The G protein-gated potassium current I (K, ACh) is constitutively active in patients with chronic atrial fibrillation. Circulation 2005; 112: 3697–3706.

14. Sossalla S, Kallmeyer B, Wagner S et al. Altered Na+ currents in atrial fibrillation effects of ranolazine on arrhythmias and contracitility in human atrial myocardium. J Am Coll Cardiol 2010; 55: 2330–2342.

15. Mao ZL, Wheeler JJ, Clohs L et al. Pharmacokinetics of novel atrial-selective antiarrhythmic agent vernakalant hydrochloride injection (RSD1235): influence of CYP2D6 expression and other factors. J Clin Pharm 2009; 49: 17–29.

16. Cheng JW. Vernakalant in the management of atrial fibrillation. Ann Pharmacother 2008; 42: 533–542.

17. Roy D, Rowe BH, Stiell IG et al. CRAFT Investigators. A randomized, controlled trial of RSD1235, a novel antiarrhythmic agent in the treatment of recent onset of atrial fibrillation. J Am Coll Cardiol 2004; 44: 2355–2361.

18. Roy D, Pratt CM, Torp-Pedersen C et al. Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a Phase III, randomized, placebo-controlled trial. Circulation 2008; 117: 1518–1525.

19. Pratt CM, Roy D, Torp-Pedersen C et al. Atrial Arrhythmia Conversion Trial (ACT-III) Investigators. Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation. Am J Cardiol 2010; 106: 1277–1283.

20. Kowey PR, Roy D, Pratt CM et al. Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial. Circ Arrhythm Electrophysiol 2009; 2: 652–659.

21. Stiell IG, Roos JS, Kavanagh KM et al. A multicenter, open label study of vernakalant for the conversion of atrial fibrillation to sinus rhythm. Am Heart J 2010; 159: 1095–1101.

22. Camm AJ, Capucci A, Hohnloser S et al. AVRO Investigators. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent onset atrial fibrillation. J Am Coll Cardiol 2011; 57: 313–321.

23. Dorian P, Pinter A, Mangat I et al. The effect of vernakalant (RSD1235), an investigational antiarrhythmic agent, on atrial electrophysiology in humans. J Cardiovasc Pharmacol 2007; 50: 35–40.

24. European Medicines Agency. Assessment report for Brinavess. www.ema.europa.eu/docs/en_GB/ Document_library/EPAR__Public_assessment_report/human/001215/WC500097150.pdf (Assessed 12 Dec 2010).

25. Tian D, Frishman WH. Vernakalant: a new drug to treat patients with acute onset atrial fibrillation. Cardiol Rev 2011; 19: 41–44.

26. Kochiadakis GE, Igoumenidis NE, Hamilos ME et al. A comparative study of the efficacy and safety of procainamide versus propafenone versus amiodarone for the conversion of recent-onset atrial fibrillation. Am J Cardiol 2007; 99: 1721–1725.

27. Boriani G, Diemberger I, Biffi M et al. Pharmacological cardioversion of atrial fibrillation: current management and treatment options. Drugs 2004; 64: 2741–2762.

28. Alp NJ, Bell JA, Shahi M. Randomized double blind trial of oral versus intravenous flecainide for the cardioversion of acute atrial fibrillation. Heart 2000; 84: 37–40.

29. Ellenbogen KA, Clemo HF, Stambler BS et al. Efficacy of ibutilide for termination of atrial fibrillation and flutter. Am J Cardiol 1996; 78: 42–45.