- Email: [email protected]
Is vernakalant better or not compared with other treatments for conversion acute atrial fibrillation?
International Journal of Cardiology 169 (2013) 95–96
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Editorial
Is vernakalant better or not compared with other treatments for conversion acute atrial fibrillation? Diego Conde ⁎ Instituto Cardiovascular de Buenos Aires, Blanco Encalada 1543, 1428 Buenos Aires, Argentina
a r t i c l e
i n f o
Article history: Received 28 July 2013 Accepted 30 August 2013 Available online 5 September 2013 Keywords: Vernakalant Propafenone Flecainide Amiodarone Electrical cardioversion Atrial fibrillation
a b s t r a c t Vernakalant has proved to be more rapid in converting recent onset AF to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide. In many centers around the world the electrical cardioversion is the first line of treatment of acute atrial fibrillation. Recently a group published that vernakalant had a 90% conversion rate in patients with recent onset atrial fibrillation without structural heart disease versus 100% conversion rate in the electrical cardioversion group. In this study there was no statistical differences between both groups (p = NS). Vernakalant has been approved in Europe and South America, but it has not been approved in the United States and Canada. FDA wants a megatrial to show the real benefits of vernakalant compared to other drugs including electrical cardioversion. The trial ACT V has been canceled because one patient who received vernakalant died and this is the reason why FDA has not approved vernakalant yet. We do not know the real condition of the patient and if it was corrected to conclude that the severe adverse event had a direct relationship with the drug. I can conclude that it is time to design a megatrial to show if vernakalant is better or not for conversion of recent onset atrial fibrillation compared with other antiarrhythmic drugs and electrical cardioversion because all the topics about this drug have been published but in brief reports. We need a big trial to know the real safety of this drug. © 2013 Elsevier Ireland Ltd. All rights reserved.
Recent onset AF is a frequent cause for presentation to the emergency department [1]. Conversion of recent onset AF to sinus rhythm with antiarrhythmic drugs reduces the risk of hemodynamic instability, hospitalizations and atrial remodeling seen with persistent AF [2]. Boriani et al. compared oral loading dose of propafenone 600 mg with intravenous propafenone and placebo. At 8 h either intravenous or oral propafenone were effective in almost two thirds of the patients with a statistical difference versus placebo [3]. Khan showed that a single oral dose of flecainide 300 mg had a similar time to conversion of AF to sinus rhythm to intravenous drugs class IC [4]. This is the reason why an oral loading dose of propafenone 600 mg or a single dose of flecainide 300 mg are used around the world for conversion of recent onset AF in patients without structural heart disease. Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent that is used intravenously, prolongs the atrial refractory period but has little effect on ventricular repolarization. It is a multi-ion channel blocker blocking early-activating potassium channels combined ⁎ Tel.: +54 91163816339; fax: +54 1147877533. E-mail address: [email protected]. 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.08.139
with concentration-, voltage- and frequency-dependent blockade of sodium channels. It has a rapid distribution and onset of action with a mean half-life elimination of 3 h. Plasma concentrations decline approximately 50% in 10 min. Restoration of sinus rhythm occurs within 90 min in 50% of cases [5–8]. Vernakalant produced a rapid conversion according to the results of the CRAFT study [5] (versus placebo) or AVRO study [8] (versus amiodarone). Vernakalant has proved to be more rapid in converting recent onset AF to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide [5,8–10]. At the same time vernakalant showed to have a better change of perception of state of health from screening to hour 2 in a clinical study, where it was compared with flecainide and propafenone [11]. In many centers around the world the electrical cardioversion is the first line of treatment of acute atrial fibrillation. Recently a group published that vernakalant had a 90% conversion rate in patients with recent onset atrial fibrillation without structural heart disease versus 100% conversion rate in the electrical cardioversion group. In this study there was no statistical differences between both groups (p = NS), with a benefit for vernakalant group avoiding sedation and fasting of 3 to 6 h compared with electrical cardioversion [12].
96
Editorial
Vernakalant has been approved in Europe and South America, but it has not been approved in the United States and Canada. FDA wants a big trial to show the real benefits of vernakalant compared to other drugs including electrical cardioversion. The trial ACT V has been canceled because one patient who received vernakalant died and this is the reason why FDA has not approved vernakalant yet. We do not know the real condition of the patient and if it was corrected to conclude that the severe adverse event had a direct relationship with the drug. I can conclude that it is time to design a big trial to show if vernakalant is better or not for conversion of recent onset atrial fibrillation compared with other antiarrhythmic drugs and electrical cardioversion because all the topics about this drug have been published but in brief reports. We need a big trial to know the real safety of this drug. References [1] Go A, Hylek E, Phillips K, 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;285:2370–5. [2] Li H, Easley A, Barrington W, Windle J. Evaluation and management of atrial fibrillation in the emergency department. Emerg Med Clin North Am 1998;16:389–403.
[3] Boriani G, Capucci A, Lenzi T, Sanguinetti M, Magnani B. Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration. Chest 1995;108:355–8. [4] Khan IA. Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542–7. [5] Roy D, Rowe BH, Stiell IG, et al. A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation. J Am Coll Cardiol 2004;44:2355–61. [6] Roy D, Pratt C, Torp-Pedersen C, et al. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial. Circulation 2008;117(12):1518–25. [7] Kowey P, Dorian P, Mitchell L, et al. Vernakalant hydrochloride for rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double blind, placebocontrolled trial. Circ Arrhythm Electrophysiol 2009;2:652–9. [8] Camm AJ, Capucci A, Hohnloser SH, et al. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol 2011;57:313–21. [9] Conde D, Costabel JP, Aragon M, et al. Propafenone versus vernakalant for conversion of recent-onset atrial fibrillation. Cardiovasc Ther May 20 2013. http://dx.doi.org/ 10.1111/1755-5922.12036. [10] Conde D, Costabel JP, Caro M, et al. Flecainide versus vernakalant for conversion of recent-onset atrial fibrillation. Int J Cardiol 2013;57:2423–5. [11] Conde D, Costabel JP, Aragon M, Lambardi F, Trivi M. Vernakalant: perception of state of health in patients with a recent-onset atrial fibrillation. Cardiol J 2013. http://dx.doi.org/10.5603/CJ.a2013.0113. [12] Conde D, Lalor N, Rodriguez L, Elissamburu P, Trivi M. Vernakalant versus electrical cardioversion in recent-onset atrial fibrillation. Int J Cardiol 2013;168:4431–2.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Editorial
Is vernakalant better or not compared with other treatments for conversion acute atrial fibrillation? Diego Conde ⁎ Instituto Cardiovascular de Buenos Aires, Blanco Encalada 1543, 1428 Buenos Aires, Argentina
a r t i c l e
i n f o
Article history: Received 28 July 2013 Accepted 30 August 2013 Available online 5 September 2013 Keywords: Vernakalant Propafenone Flecainide Amiodarone Electrical cardioversion Atrial fibrillation
a b s t r a c t Vernakalant has proved to be more rapid in converting recent onset AF to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide. In many centers around the world the electrical cardioversion is the first line of treatment of acute atrial fibrillation. Recently a group published that vernakalant had a 90% conversion rate in patients with recent onset atrial fibrillation without structural heart disease versus 100% conversion rate in the electrical cardioversion group. In this study there was no statistical differences between both groups (p = NS). Vernakalant has been approved in Europe and South America, but it has not been approved in the United States and Canada. FDA wants a megatrial to show the real benefits of vernakalant compared to other drugs including electrical cardioversion. The trial ACT V has been canceled because one patient who received vernakalant died and this is the reason why FDA has not approved vernakalant yet. We do not know the real condition of the patient and if it was corrected to conclude that the severe adverse event had a direct relationship with the drug. I can conclude that it is time to design a megatrial to show if vernakalant is better or not for conversion of recent onset atrial fibrillation compared with other antiarrhythmic drugs and electrical cardioversion because all the topics about this drug have been published but in brief reports. We need a big trial to know the real safety of this drug. © 2013 Elsevier Ireland Ltd. All rights reserved.
Recent onset AF is a frequent cause for presentation to the emergency department [1]. Conversion of recent onset AF to sinus rhythm with antiarrhythmic drugs reduces the risk of hemodynamic instability, hospitalizations and atrial remodeling seen with persistent AF [2]. Boriani et al. compared oral loading dose of propafenone 600 mg with intravenous propafenone and placebo. At 8 h either intravenous or oral propafenone were effective in almost two thirds of the patients with a statistical difference versus placebo [3]. Khan showed that a single oral dose of flecainide 300 mg had a similar time to conversion of AF to sinus rhythm to intravenous drugs class IC [4]. This is the reason why an oral loading dose of propafenone 600 mg or a single dose of flecainide 300 mg are used around the world for conversion of recent onset AF in patients without structural heart disease. Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent that is used intravenously, prolongs the atrial refractory period but has little effect on ventricular repolarization. It is a multi-ion channel blocker blocking early-activating potassium channels combined ⁎ Tel.: +54 91163816339; fax: +54 1147877533. E-mail address: [email protected]. 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.08.139
with concentration-, voltage- and frequency-dependent blockade of sodium channels. It has a rapid distribution and onset of action with a mean half-life elimination of 3 h. Plasma concentrations decline approximately 50% in 10 min. Restoration of sinus rhythm occurs within 90 min in 50% of cases [5–8]. Vernakalant produced a rapid conversion according to the results of the CRAFT study [5] (versus placebo) or AVRO study [8] (versus amiodarone). Vernakalant has proved to be more rapid in converting recent onset AF to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide [5,8–10]. At the same time vernakalant showed to have a better change of perception of state of health from screening to hour 2 in a clinical study, where it was compared with flecainide and propafenone [11]. In many centers around the world the electrical cardioversion is the first line of treatment of acute atrial fibrillation. Recently a group published that vernakalant had a 90% conversion rate in patients with recent onset atrial fibrillation without structural heart disease versus 100% conversion rate in the electrical cardioversion group. In this study there was no statistical differences between both groups (p = NS), with a benefit for vernakalant group avoiding sedation and fasting of 3 to 6 h compared with electrical cardioversion [12].
96
Editorial
Vernakalant has been approved in Europe and South America, but it has not been approved in the United States and Canada. FDA wants a big trial to show the real benefits of vernakalant compared to other drugs including electrical cardioversion. The trial ACT V has been canceled because one patient who received vernakalant died and this is the reason why FDA has not approved vernakalant yet. We do not know the real condition of the patient and if it was corrected to conclude that the severe adverse event had a direct relationship with the drug. I can conclude that it is time to design a big trial to show if vernakalant is better or not for conversion of recent onset atrial fibrillation compared with other antiarrhythmic drugs and electrical cardioversion because all the topics about this drug have been published but in brief reports. We need a big trial to know the real safety of this drug. References [1] Go A, Hylek E, Phillips K, 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;285:2370–5. [2] Li H, Easley A, Barrington W, Windle J. Evaluation and management of atrial fibrillation in the emergency department. Emerg Med Clin North Am 1998;16:389–403.
[3] Boriani G, Capucci A, Lenzi T, Sanguinetti M, Magnani B. Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration. Chest 1995;108:355–8. [4] Khan IA. Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542–7. [5] Roy D, Rowe BH, Stiell IG, et al. A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation. J Am Coll Cardiol 2004;44:2355–61. [6] Roy D, Pratt C, Torp-Pedersen C, et al. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial. Circulation 2008;117(12):1518–25. [7] Kowey P, Dorian P, Mitchell L, et al. Vernakalant hydrochloride for rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double blind, placebocontrolled trial. Circ Arrhythm Electrophysiol 2009;2:652–9. [8] Camm AJ, Capucci A, Hohnloser SH, et al. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol 2011;57:313–21. [9] Conde D, Costabel JP, Aragon M, et al. Propafenone versus vernakalant for conversion of recent-onset atrial fibrillation. Cardiovasc Ther May 20 2013. http://dx.doi.org/ 10.1111/1755-5922.12036. [10] Conde D, Costabel JP, Caro M, et al. Flecainide versus vernakalant for conversion of recent-onset atrial fibrillation. Int J Cardiol 2013;57:2423–5. [11] Conde D, Costabel JP, Aragon M, Lambardi F, Trivi M. Vernakalant: perception of state of health in patients with a recent-onset atrial fibrillation. Cardiol J 2013. http://dx.doi.org/10.5603/CJ.a2013.0113. [12] Conde D, Lalor N, Rodriguez L, Elissamburu P, Trivi M. Vernakalant versus electrical cardioversion in recent-onset atrial fibrillation. Int J Cardiol 2013;168:4431–2.