J Atr Fibrillation. 2008;1(2):98-107. doi: 10.4022/jafib.v1i1.400.

How Do Atrial-Selective Drugs Differ From Antiarrhythmic Drugs Currently Used in the Treatment of Atrial Fibrillation?.

Journal of atrial fibrillation

Alexander Burashnikov, Charles Antzelevitch

PMID: 21057583 PMCID: PMC2970929 DOI: 10.4022/jafib.v1i1.400

Abstract

Current pharmacologic strategies for the management of Atrial fibrillation (AF) include use of 1) sodium channel blockers, which are contraindicated in patients with coronary artery or structural heart disease because of their potent effect to slow conduction in the ventricles, 2) potassium channel blockers, which predispose to acquired long QT and Torsade de Pointes arrhythmias because of their potent effect to prolong ventricular repolarization, and 3) mixed ion channel blockers such as amiodarone, which are associated with multi-organ toxicity. Accordingly, recent studies have focused on agents that selectively affect the atria but not the ventricles. Several Atrial-selective approaches have been proposed for the management of AF, including inhibition of the Atrial-specific ultra rapid delayed rectified potassium current (IKur), acetylcholine-regulated inward rectifying potassium current (IK-ACh), or connexin-40 (Cx40). All three are largely exclusive to atria. Recent studies have proposed that an Atrial-selective depression of sodium channel-dependent parameters with agents such as ranolazine may be an alternative approach capable of effectively suppressing AF without increasing susceptibility to ventricular arrhythmias. Clinical evidence for Cx40 modulation or IK-ACh inhibition are lacking at this time. The available data suggest that Atrial-selective approaches involving a combination of INa, IKur, IKr, and, perhaps, Ito block may be more effective in the management of AF than pure IKur or INa block. The anti-AF efficacy of the Atrial-selective/predominant agents appears to be similar to that of conventionally used anti-AF agents, with the major apparent difference being that the latter are associated with ventricular arrhythmogenesis and extra cardiac toxicity.

References

1. Pacing Clin Electrophysiol. 1995 Sep;18(9 Pt 1):1686-704 - PubMed
2. Ann N Y Acad Sci. 2008 Mar;1123:105-12 - PubMed
3. J Cardiovasc Electrophysiol. 1999 Aug;10(8):1124-52 - PubMed
4. J Pharmacol Exp Ther. 2005 Dec;315(3):1362-7 - PubMed
5. J Physiol. 1996 Feb 15;491 ( Pt 1):31-50 - PubMed
6. Heart Rhythm. 2006 Nov;3(11):1321-31 - PubMed
7. J Cardiovasc Pharmacol. 2007 Jul;50(1):35-40 - PubMed
8. Circulation. 2007 Oct 9;116(15):1647-52 - PubMed
9. J Am Coll Cardiol. 2006 Aug 15;48(4):854-906 - PubMed
10. Cardiovasc Res. 2005 Jul 1;67(1):69-76 - PubMed
11. Expert Opin Investig Drugs. 2007 Apr;16(4):519-32 - PubMed
12. J Cardiovasc Electrophysiol. 2007 Dec;18(12):1313-20 - PubMed
13. Circulation. 2008 Mar 25;117(12):1518-25 - PubMed
14. J Cardiovasc Pharmacol. 1996 Apr;27(4):594-600 - PubMed
15. Pharmacol Res. 2006 Aug;54(2):136-41 - PubMed
16. Circulation. 2002 Jun 11;105(23):2753-9 - PubMed
17. Cardiovasc Res. 2007 Jun 1;74(3):426-37 - PubMed
18. J Cardiovasc Pharmacol. 1992 Dec;20(6):913-22 - PubMed
19. Circ Res. 1993 Dec;73(6):1061-76 - PubMed
20. Circulation. 1994 Oct;90(4):2032-40 - PubMed
21. J Pharmacol Exp Ther. 1998 Apr;285(1):135-42 - PubMed
22. J Physiol. 2004 Jun 1;557(Pt 2):583-97 - PubMed
23. J Mol Cell Cardiol. 2002 Sep;34(9):1185-94 - PubMed
24. Cardiovasc Res. 1999 Oct;44(1):121-31 - PubMed
25. Circulation. 2007 Sep 25;116(13):1449-57 - PubMed
26. Nat Rev Drug Discov. 2006 Dec;5(12):1034-49 - PubMed
27. Circulation. 2000 Mar 14;101(10):1179-84 - PubMed
28. J Cardiovasc Pharmacol. 2002 Jan;39(1):29-38 - PubMed
29. Circulation. 2005 Dec 13;112(24):3697-706 - PubMed
30. Med Sci Monit. 2004 Jul;10(7):BR221-8 - PubMed
31. J Pharmacol Exp Ther. 2008 Jan;324(1):322-30 - PubMed
32. J Cardiovasc Pharmacol. 2007 Apr;49(4):197-206 - PubMed
33. Circulation. 2001 Nov 20;104(21):2551-7 - PubMed
34. Pacing Clin Electrophysiol. 2006 Mar;29(3):290-5 - PubMed
35. J Cardiovasc Pharmacol. 2007 Apr;49(4):236-45 - PubMed
36. J Cardiovasc Pharmacol. 2008 Aug;52(2):121-8 - PubMed
37. Circulation. 2006 Apr 11;113(14):1730-7 - PubMed
38. Cardiovasc Res. 2003 Nov 1;60(2):298-306 - PubMed
39. J Cardiovasc Electrophysiol. 2004 Dec;15(12):1444-50 - PubMed
40. J Pharmacol Sci. 2005 May;98(1):33-40 - PubMed
41. Am J Cardiol. 1982 Nov;50(5):1082-6 - PubMed
42. Hum Mol Genet. 2006 Jul 15;15(14):2185-91 - PubMed
43. J Am Coll Cardiol. 2008 Feb 26;51(8):787-92 - PubMed
44. Circulation. 2004 Oct 19;110(16):2299-306 - PubMed
45. J Am Coll Cardiol. 2004 Mar 17;43(6):994-1000 - PubMed
46. J Cardiovasc Pharmacol. 2006 Jan;47(1):123-32 - PubMed
47. Circulation. 2004 Sep 28;110(13):1717-24 - PubMed
48. Circulation. 2004 Jan 27;109(3):327-34 - PubMed
49. Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2393-400 - PubMed
50. J Cardiovasc Electrophysiol. 1996 Feb;7(2):113-9 - PubMed
51. Heart Rhythm. 2008 Sep;5(9):1304-9 - PubMed

Publication Types

• Journal Article

Grant support

• R01 HL047678/HL/NHLBI NIH HHS/United States
• R01 HL047678-15/HL/NHLBI NIH HHS/United States