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Other Antiarrhythmic Drugs

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Antiarrhythmic Drugs

Part of the book series: Current Cardiovascular Therapy ((CCT))

Abstract

In previous chapters of this book analyze the antiarrhythmic drugs (AADs) classified in groups I-IV according to the Vaughan-Williams classification. However, some old (adenosine, digoxin) and new AADs (ivabradine, ranolazine, vernakalant) were not listed in any of the original four classes. Therefore, in this chapter, we shall review the electrophysiological effects of these drugs (Table 6.1). Their electrophysiological and pharmacokinetic properties, adverse effects and clinical indications are summarized in Tables 6.2, 6.3, 6.4, 6.5, 6.6, and 6.7.

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References

  1. DiMarco JP. Adenosine and digoxin. In: Zipes DP, Jalife J, editors. Cardiac electrophysiology: from cell to bedside. 3rd ed. Philadelphia: Saunders; 2000. p. 933–8.

    Google Scholar 

  2. Layland J, Carrick D, Lee M, Oldroyd K, Berry C. Adenosine. Physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv. 2014;7:581–91.

    Article  PubMed  Google Scholar 

  3. Lerman BB, Markowitz SM, Cheung JW, Liu CF, Thomas G, Ip JE. Supraventricular tachycardia. Mechanistic insights deduced from adenosine. Circ Arrhythm Electrophysiol. 2018;11:e006953.

    Article  PubMed  Google Scholar 

  4. DiMarco JP, Miles W, Akhtar M, Milstein S, Sharma AD, Platia E, et al. Adenosine for paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Assessment in placebo-controlled, multicenter trials. The Adenosine for PSVT Study Group. Ann Intern Med. 1990;113:104–10.

    Article  CAS  PubMed  Google Scholar 

  5. Camm AJ, Garratt CJ. Adenosine and supraventricular tachycardia. N Engl J Med. 1991;325:1621–9.

    Article  CAS  PubMed  Google Scholar 

  6. Brady WJ, DeBehnke DJ, Wickman LL, Lindbeck G. Treatment of out-of-hospital supraventricular tachycardia: adenosine vs verapamil. Acad Emerg Med. 1996;3:574–85.

    Article  PubMed  Google Scholar 

  7. Markowitz SM, Stein KM, Mittal S, Slotwtner DJ, Lerman BB. Differential effects of adenosine on focal and macroreentrant atrial tachycardia. J Cardiovasc Electrophysiol. 1999;10:489–502.

    Article  CAS  PubMed  Google Scholar 

  8. Glatter KA, Cheng J, Dorostkar P, Modin G, Talwar S, Al-Nimri M, et al. Electrophysiologic effects of adenosine in patients with supraventricular tachycardia. Circulation. 1999;99:1034–40.

    Article  CAS  PubMed  Google Scholar 

  9. Delaney B, Loy J, Kelly A-M. The relative efficacy of adenosine versus verapamil for the treatment of stable paroxysmal supraventricular tachycardia in adults: a meta-analysis. Eur J Emerg Med. 2011;18:148–52.

    Article  PubMed  Google Scholar 

  10. Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2016;67:1575–623.

    Article  PubMed  Google Scholar 

  11. Brugada J, Katritsis DG, Arbelo E, Arribas F, Bax JJ, Blomström-Lundqvist C, et al.; ESC Scientific Document Group. 2019 ESC guidelines for the management of patients with supraventricular tachycardia. The Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J. 2019. pii: ehz467. https://doi.org/10.1093/eurheartj/ehz467.

  12. Kall JG, Kopp D, Olshansky B, Kinder C, O’Connor M, Cadman CS, et al. Adenosine-sensitive atrial tachycardia. Pacing Clin Electrophysiol. 1995;18:300–6.

    Google Scholar 

  13. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESCEndorsed by the European Stroke Organisation (ESO). Eur Heart J. 2016;37:2893–962.

    Article  PubMed  Google Scholar 

  14. Pelleg A, Pennock RS, Kutalek SP. Proarrhythmic effects of adenosine: one decade of clinical data. Am J Ther. 2002;9:141–7.

    Article  PubMed  Google Scholar 

  15. Fragakis N, Antoniadis AP, Korantzopoulos P, Kyriakou P, Koskinas KC, Geleris P. Sinus nodal response to adenosine relates to the severity of sinus node dysfunction. Europace. 2012;14:859–64.

    Article  PubMed  Google Scholar 

  16. Ellenbogen KA, Thames MD, DiMarco JP, Sheehan H, Lerman BB. Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity. Circulation. 1990;81:821–8.

    Article  CAS  PubMed  Google Scholar 

  17. Ip JE, Cheung JW, Chung JH, Liu CF, Thomas G, Markowitz SM, et al. Adenosine-induced atrial fibrillation. Insights into mechanism. Circ Arrhythm Electrophysiol. 2013;6:e34–7.

    PubMed  Google Scholar 

  18. Li N, Csepe TA, Hansen BJ, Sul LV, Kalyanasundaram A, Zakharkin SO, et al. Adenosine-induced atrial fibrillation. Localized reentrant drivers in lateral right atria due to heterogeneous expression of adenosine A1 receptors and GIRK4 subunits in the human heart. Circulation. 2016;134:486–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Garratt CJ, Griffith MJ, O’Nunain S, Ward DE, Camm AJ. Effects of intravenous adenosine on antegrade refractoriness of accessory atrioventricular connections. Circulation. 1991;84:1962–8.

    Article  CAS  PubMed  Google Scholar 

  20. Tamargo J, Caballero R, Delpón E. Cardiovascular drugs-from A to Z. In: Kaski JC, Kjeldsen KP, editors. The ESC handbook on cardiovascular pharmacotherapy. Oxford: Oxford University Press; 2019. p. 423–808.

    Google Scholar 

  21. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cıfkova R, De Bonis M, et al. ESC Scientific Document Group. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39:3165–241.

    Article  PubMed  Google Scholar 

  22. Müller C, Jacobson KA. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta. 2011;1808:1290–308.

    Article  PubMed  CAS  Google Scholar 

  23. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–33.

    Article  Google Scholar 

  24. Gheorghiade M, van Veldhuisen DJ, Colucci WS. Contemporary use of digoxin in the management of cardiovascular disorders. Circulation. 2006;113:2556–64.

    Article  PubMed  Google Scholar 

  25. Tamargo J, Delpón E, Caballero R. The safety of digoxin as a pharmacological treatment of atrial fibrillation. Expert Opin Drug Saf. 2006;5:453–67.

    Article  CAS  PubMed  Google Scholar 

  26. Arispe N, Diaz JC, Simakova S, Pollard HB. Digitoxin induces calcium uptake into cells by forming transmembrane calcium channels. Proc Natl Acad Sci U S A. 2008;105:2610–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071–4.

    Article  PubMed  Google Scholar 

  28. Sellers TD Jr, Bashore TM, Gallagher JJ. Digitalis in the pre-excitation syndrome. Analysis during atrial fibrillation. Circulation. 1977;56:260–7.

    Article  PubMed  Google Scholar 

  29. Sheinman BD, Evans T. Acceleration of ventricular rate by fibrillation associated with the Wolff-Parkinson-White syndrome. Br Med J (Clin Res Ed). 1982;285:999–1000.

    Article  CAS  Google Scholar 

  30. Khand AU, Rankin AC, Martin W, Taylor J, Gemmell I, Cleland JG. Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? J Am Coll Cardiol. 2003;42:1944–51.

    Article  CAS  PubMed  Google Scholar 

  31. Shettiggar UR, Toole JG, Appunn DO. Combined use of esmolol and digoxin in the acute treatment of atrial fibrillation or flutter. Am Heart J. 1993;126:368–74.

    Article  Google Scholar 

  32. Roy D, Talajic M, Nattel S, Atrial Fibrillation and Congestive Heart Failure Investigators, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667–77.

    Article  CAS  PubMed  Google Scholar 

  33. Deedwania PC, Singh BN, Ellenbogen K, Fisher S, Fletcher R, Singh SN. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation. 1998;98:2574–9.

    Article  CAS  PubMed  Google Scholar 

  34. Turakhia MP, Santangeli P, Winkelmayer WC, Xu X, Ullal AJ, Than CT, et al. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study. J Am Coll Cardiol. 2014;64:660–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vamos M, Erath JW, Hohnloser SH. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J. 2015;36:1831–8.

    Article  CAS  PubMed  Google Scholar 

  36. Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, et al. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ahmed A, Rich MW, Love TE, Lloyd-Jones DM, Aban IB, Colucci WS, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27:178–86.

    Article  CAS  PubMed  Google Scholar 

  38. Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiological basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8:1281–90.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Fedida D. Vernakalant (RSD1235): a novel, atrial-selective antifibrillatory agent. Expert Opin Investig Drugs. 2007;16:519–32.

    Article  CAS  PubMed  Google Scholar 

  40. Guerra F, Matassini MV, Scappini L, Urbinati A, Capucci A. Intravenous vernakalant for the rapid conversion of recent onset atrial fibrillation: systematic review and meta-analysis. Expert Rev Cardiovasc Ther. 2014;12:1067–75.

    Article  CAS  PubMed  Google Scholar 

  41. Akel T, Lafferty J. Efficacy and safety of intravenous vernakalant for the rapid conversion of recent-onset atrial fibrillation: a meta-analysis. Ann Noninvasive Electrocardiol. 2018;23:e12508.

    Article  PubMed  Google Scholar 

  42. Camm AJ, Capucci A, Hohnloser SH, Torp-Pedersen C, Van Gelder IC, Mangal B, 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.

    Article  PubMed  CAS  Google Scholar 

  43. Tamargo J, Caballero R, Delpón E. Ranolazine: an antianginal drug with antiarrhythmic properties. Expert Rev Cardiovasc Ther. 2011;9:815–27.

    Article  CAS  PubMed  Google Scholar 

  44. Bengel P, Ahmad S, Sossalla S. Inhibition of late sodium current as an innovative antiarrhythmic strategy. Curr Heart Fail Rep. 2017;14:179–86.

    Article  CAS  PubMed  Google Scholar 

  45. Gong M, Zhang Z, Fragakis N, Korantzopoulos P, Letsas KP, Li G, et al. Role of ranolazine in the prevention and treatment of atrial fibrillation: a meta-analysis of randomized clinical trials. Heart Rhythm. 2017;14:3–1.

    Article  PubMed  Google Scholar 

  46. White CM, Nguyen E. Novel use of ranolazine as an antiarrhythmic agent in atrial fibrillation. Ann Pharmacother. 2017;51:245–52.

    Article  CAS  PubMed  Google Scholar 

  47. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297:1775–83.

    Article  CAS  PubMed  Google Scholar 

  48. De Ferrari GM, Maier LS, Mont L, Schwartz PJ, Simonis G, Leschke M, et al. RAFFAELLO Investigators. Ranolazine in the treatment of atrial fibrillation: results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study. Heart Rhythm. 2015;12:872–8.

    Article  PubMed  Google Scholar 

  49. Reiffel JA, Camm AJ, Belardinelli L, Zeng D, Karwatowska-Prokopczuk E, Olmsted A, et al. HARMONY Investigators. The HARMONY Trial: combined ranolazine and dronedarone in the management of paroxysmal atrial fibrillation: mechanistic and therapeutic synergism. Circ Arrhythm Electrophysiol. 2015;8:1048–56.

    Article  CAS  PubMed  Google Scholar 

  50. Moss AJ, Zareba W, Schwarz KQ, Rosero S, McNitt S, Robinson JL. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol. 2008;19:1289–93.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Priori S, Blomstroöm-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2015;36:2793–867.

    Article  PubMed  Google Scholar 

  52. Koruth JS, Lala A, Pinney S, Reddy VY, Dukkipati SR. The clinical use of ivabradine. J Am Coll Cardiol. 2017;70:1777–84.

    Article  PubMed  Google Scholar 

  53. Cappato R, Castelvecchio S, Ricci C, Bianco E, Vitali-Serdoz L, Gnecchi-Ruscone T, et al. Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation. J Am Coll Cardiol. 2012;60:1323–9.

    Article  CAS  PubMed  Google Scholar 

  54. Ptaszynski P, Kaczmarek K, Ruta J, et al. Metoprolol succinate vs. ivabradine in the treatment of inappropriate sinus tachycardia in patients unresponsive to previous pharmacological therapy. Europace. 2013;15:116–21.

    Article  PubMed  Google Scholar 

  55. Sheldon RS, Grubb BP 2nd, Olshansky B, Shen WK, Calkins H, Brignole M, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12:e41–63.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dias da Silva VJ, Tobaldini E, Rocchetti M, Wu MA, Malfatto G, Montano N, et al. Modulation of sympathetic activity and heart rate variability by ivabradine. Cardiovasc Res. 2015;108:31–8.

    Article  PubMed  Google Scholar 

  57. Kleber AG, Rudy Y. Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol Rev. 2004;84:431–88.

    Article  CAS  PubMed  Google Scholar 

  58. Noorman M, van der Heyden MA, van Veen TA, Cox MG, Hauer RN, de Bakker JM, et al. Cardiac cell-cell junctions in health and disease: electrical versus mechanical coupling. J Mol Cell Cardiol. 2009;47:23–31.

    Article  CAS  PubMed  Google Scholar 

  59. Dhein S, Hagen A, Jozwiak J, Dietze A, Garbade J, Barten M, et al. Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides. Naunyn Schmiedeberg’s Arch Pharmacol. 2010;381:221–34.

    Google Scholar 

  60. Shattock MJ, Ottolia M, Bers M, Blaustein MP, Boguslavskyi A, Bossuyt J, et al. Na+/Ca2+ exchange and Na+/K+-ATPase in the heart. J Physiol. 2015;593:1361–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Antoons G, Willems R, Sipido KR. Alternative strategies in arrhythmia therapy: evaluation of Na/Ca exchange as an anti-arrhythmic target. Pharmacol Ther. 2012;134:26–42.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank P Vaquero for her invaluable technical assistance. This work was supported by grants from the Ministerio de Ciencia e Innovación (SAF2017-88116-P), Instituto de Salud Carlos III [PI16/00398 and CIBER-Cardiovascular (CB16/11/00303)] and Comunidad de Madrid (B2017/BMD-3738).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Universidad Complutense, CIBERCV, Madrid, Spain

    Juan Tamargo

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  1. Juan Tamargo
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Correspondence to Juan Tamargo .

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Editors and Affiliations

  1. Department of Cardiology, University Hospital of Sabadell, Institut d’Investigació i Innovació I3PT, University Autonoma of Barcelona, Sabadell, Spain

    Antoni Martínez-Rubio

  2. Department of Pharmacology, School of Medicine, Universidad Complutense, CIBERCV, Madrid, Spain

    Juan Tamargo

  3. “Carol Davila” University of Medicine, Colentina University Hospital, Bucharest, Romania

    Gheorghe- Andrei Dan

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Tamargo, J. (2020). Other Antiarrhythmic Drugs. In: Martínez-Rubio, A., Tamargo, J., Dan, G . (eds) Antiarrhythmic Drugs. Current Cardiovascular Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-34893-9_6

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  • DOI: https://doi.org/10.1007/978-3-030-34893-9_6

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