Skip to main content
SpringerLink
Log in

Clinical use of and future perspectives on antiarrhythmic drugs

  • Review Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Cardiac arrhythmias are associated with significant morbidity and mortality. Antiarrhythmic drug therapy was traditionally the mainstay of arrhythmia treatment; however, the limited efficacy and proarrhythmic potential of conventional antiarrhythmic drugs has generated interest in new approaches to the treatment of arrhythmias. Over the last decade, there has been improved characterization of the molecular pathways that culminate in arrhythmias. By analyzing mechanisms that increase susceptibility to arrhythmias in individuals with genetic syndromes, it might be possible to not only improve current therapies but also to develop novel approaches to treat and prevent common arrhythmias.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zheng ZJ, Croft JB, Giles WH, Mensah GA (2001) Sudden cardiac death in the United States, 1989 to 1998. Circulation 104:2158–2163

    Article  PubMed  CAS  Google Scholar 

  2. de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI, van Ree JW, Daemen MJ, Houben LG et al (1997) Out-of-hospital cardiac arrest in the 1990’s: a population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol 30:1500–1505

    Article  PubMed  Google Scholar 

  3. Huikuri HV, Castellanos A, Myerburg RJ (2001) Sudden death due to cardiac arrhythmias. N Engl J Med 345:1473–1482

    Article  PubMed  CAS  Google Scholar 

  4. Damiano RJ Jr, Gaynor SL, Bailey M, Prasad S, Cox JL, Boineau JP et al (2003) The long-term outcome of patients with coronary disease and atrial fibrillation undergoing the Cox maze procedure. J Thorac Cardiovasc Surg 126:2016–2021

    Article  PubMed  Google Scholar 

  5. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G et al (1998) Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 339:659–666

    Article  PubMed  CAS  Google Scholar 

  6. Wazni O, Martin DO, Marrouche NF, Shaaraoui M, Chung MK, Almahameed S et al (2005) C reactive protein concentration and recurrence of atrial fibrillation after electrical cardioversion. Heart 91:1303–1305

    Article  PubMed  CAS  Google Scholar 

  7. Karch MR, Zrenner B, Deisenhofer I, Schreieck J, Ndrepepa G, Dong J et al (2005) Freedom from atrial tachyarrhythmias after catheter ablation of atrial fibrillation: a randomized comparison between 2 current ablation strategies. Circulation 111:2875–2880

    Article  PubMed  Google Scholar 

  8. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al (2006) ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114:e257–e354

    Article  PubMed  Google Scholar 

  9. Cardiac Arrhythmia Suppression Trial Investigators (1989) Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. N Engl J Med 321:406–412

    Google Scholar 

  10. Krishnan SC, Antzelevitch C (1993) Flecainide-induced arrhythmia in canine ventricular epicardium Phase 2 reentry? Circulation 87:562–572

    PubMed  CAS  Google Scholar 

  11. Coromilas J, Saltman AE, Waldecker B, Dillon SM, Wit AL (1995) Electrophysiological effects of flecainide on anisotropic conduction and reentry in infarcted canine hearts. Circulation 91:2245–2263

    PubMed  CAS  Google Scholar 

  12. Antzelevitch C, Brugada P, Brugada J, Brugada R (2005) Brugada syndrome: from cell to bedside. Curr Probl Cardiol 30:9–54

    Article  PubMed  Google Scholar 

  13. The Sicilian Gambit (1991) A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Circulation 84:1831–1851

    Google Scholar 

  14. Singh BN, Vaughan Williams EM (1970) A third class of anti-arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474. Br J Pharmacol 39:675–687

    PubMed  CAS  Google Scholar 

  15. Dangman KH, Hoffman BF (1981) In vivo and in vitro antiarrhythmic and arrhythmogenic effects of N-acetyl procainamide. J Pharmacol Exp Ther 217:851–862

    PubMed  CAS  Google Scholar 

  16. Katritsis D, Camm AJ (1993) New class III antiarrhythmic drugs. Eur Heart J 14(Suppl H):93–99

    PubMed  CAS  Google Scholar 

  17. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF et al (1996) Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet 348:7–12

    Article  PubMed  CAS  Google Scholar 

  18. Kober L, Bloch Thomsen PE, Moller M, Torp-Pedersen C, Carlsen J, Sandoe E et al (2000) Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet 356:2052–2058

    Article  PubMed  CAS  Google Scholar 

  19. Camm AJ, Pratt CM, Schwartz PJ, Al-Khalidi HR, Spyt MJ, Holroyde MJ et al (2004) Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification. Circulation 109:990–996

    Article  PubMed  Google Scholar 

  20. Roden DM (2004) Drug-induced prolongation of the QT interval. N Engl J Med 350:1013–1022

    Article  PubMed  CAS  Google Scholar 

  21. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 304:801–807

  22. Propranolol after myocardial infarction. JAMA 248:2833–2834

  23. Murray KT, Mace LC, Yang Z (2007) Nonantiarrhythmic drug therapy for atrial fibrillation. Heart Rhythm 4:S88–S90

    Article  PubMed  Google Scholar 

  24. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R et al (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation 105:1897–1903

    Article  PubMed  CAS  Google Scholar 

  25. Brouwer IA, Geelen A, Katan MB (2006) n-3 Fatty acids, cardiac arrhythmia and fatal coronary heart disease. Prog Lipid Res 45:357–367

    Article  PubMed  CAS  Google Scholar 

  26. Mozaffarian D, Psaty BM, Rimm EB, Lemaitre RN, Burke GL, Lyles MF et al (2004) Fish intake and risk of incident atrial fibrillation. Circulation 110:368–373

    Article  PubMed  Google Scholar 

  27. Boos CJ, Anderson RA, Lip GY (2006) Is atrial fibrillation an inflammatory disorder? Eur Heart J 27:136–149

    Article  PubMed  Google Scholar 

  28. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:145–153

    Article  PubMed  CAS  Google Scholar 

  29. Mitchell LB, Powell JL, Gillis AM, Kehl V, Hallstrom AP (2003) Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 42:81–87

    Article  PubMed  CAS  Google Scholar 

  30. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A et al (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341:709–717

    Article  PubMed  CAS  Google Scholar 

  31. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C (1999) Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 100:376–380

    PubMed  CAS  Google Scholar 

  32. L’Allier PL, Ducharme A, Keller PF, Yu H, Guertin MC, Tardif JC (2004) Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation. J Am Coll Cardiol 44:159–164

    Article  PubMed  CAS  Google Scholar 

  33. Korantzopoulos P, Kolettis TM, Galaris D, Goudevenos JA (2007) The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation. Int J Cardiol 115:135–143

    Article  PubMed  Google Scholar 

  34. Janko S, Dorwarth U, Hoffmann E (2008) Pharmacotherapy of atrial fibrillation: an old option with new possibilities. Expert Opin Pharmacother 9:913–925

    Article  PubMed  CAS  Google Scholar 

  35. Schwartz PJ, Priori SG, Napolitano C (2003) How really rare are rare diseases?: the intriguing case of independent compound mutations in the long QT syndrome. J Cardiovasc Electrophysiol 14:1120–1121

    Article  PubMed  Google Scholar 

  36. El Yaman M, Perry J, Makielski JC, Ackerman MJ (2008) Suppression of atrial fibrillation with mexiletine pharmacotherapy in a young woman with type 1 long QT syndrome. Heart Rhythm 5:472–474

    Article  PubMed  Google Scholar 

  37. Darbar D, Roden DM, Ali MF, Yang T, Wathen MS (2005) Images in cardiovascular medicine. Himalayan T waves in the congenital long-QT syndrome. Circulation 111:e161

    Article  PubMed  Google Scholar 

  38. Gollob MH, Jones DL, Krahn AD, Danis L, Gong XQ, Shao Q et al (2006) Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med 354:2677–2688

    Article  PubMed  CAS  Google Scholar 

  39. Schwartz PJ (2006) The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med 259:39–47

    Article  PubMed  CAS  Google Scholar 

  40. Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W et al (1998) Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med 338:1248–1257

    Article  PubMed  CAS  Google Scholar 

  41. Goldenberg I, Moss AJ (2008) Long QT syndrome. J Am Coll Cardiol 51:2291–2300

    Article  PubMed  Google Scholar 

  42. Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC et al (2002) Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 105:1943–1948

    Article  PubMed  CAS  Google Scholar 

  43. Roden DM (1998) Taking the “idio” out of “idiosyncratic”: predicting torsades de pointes. Pacing Clin Electrophysiol 21:1029–1034

    Article  PubMed  CAS  Google Scholar 

  44. Splawski I, Timothy KW, Tateyama M, Clancy CE, Malhotra A, Beggs AH et al (2002) Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science 297:1333–1336

    Article  PubMed  CAS  Google Scholar 

  45. Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A et al (2007) Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 448:353–357

    Article  PubMed  CAS  Google Scholar 

  46. Mommersteeg MT, Brown NA, Prall OW, de Gier-de Vries C, Harvey RP, Moorman AF et al (2007) Pitx2c and Nkx2–5 are required for the formation and identity of the pulmonary myocardium. Circ Res 101:902–909

    Article  PubMed  CAS  Google Scholar 

  47. Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M et al (2006) A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet 38:644–651

    Article  PubMed  CAS  Google Scholar 

  48. Aarnoudse AJ, Newton-Cheh C, de Bakker PI, Straus SM, Kors JA, Hofman A et al (2007) Common NOS1AP variants are associated with a prolonged QTc interval in the Rotterdam Study. Circulation 116:10–16

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Supported in part by grants from the United States Public Health Service (HL075266, HL085690 and U01 HL65962)

Author information

Authors and Affiliations

  1. Divisions of Cardiovascular Medicine and Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, 2215B Garland Ave, 1285A MRB IV, Nashville, TN, 37323-6602, USA

    Juan Carlos Estrada & Dawood Darbar

Authors
  1. Juan Carlos Estrada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dawood Darbar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dawood Darbar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Estrada, J.C., Darbar, D. Clinical use of and future perspectives on antiarrhythmic drugs. Eur J Clin Pharmacol 64, 1139–1146 (2008). https://doi.org/10.1007/s00228-008-0555-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-008-0555-x

Keywords

Search

Navigation