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What Have We Learned from the SWORD Trial? Can Potassium Channel Blockers Reduce Sudden Cardiac Death?

  • P. J. Schwartz
Conference paper

Abstract

On November 1, 1994, the SWORD (Survival With Oral D-sotalol) trial was terminated by the Steering Committee because of an excess mortality among the patients randomized to d-sotalol. Five years after the early termination of the Cardiac Arrhythmia Suppression Trial (CAST) for similar reasons, this event has caused further concern in the field of cardiac arrhythmias and electrophysiology and is raising questions about the availability of drugs that may reduce sudden cardiac death and also about the rationale and events that precede the initiation of large-scale clinical trials.

Keywords

Heart Rate Variability Sudden Cardiac Death Ventricular Fibrillation Antiarrhythmic Drug Cardiac Arrhythmia Suppression Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    The Cardiac Arrhythmia Suppression Trial (CAST) Investigators (1989) Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 321: 406–412CrossRefGoogle Scholar
  2. 2.
    Task Force of the Working Group on Arrhythmias of the European Society of Cardiology (Akhtar M, Breithardt G, Camm AJ, Coumel P, Janse MJ, Lazzara R, Myerburg RJ, Schwartz PJ, Waldo AL, Wellens HJJ, Zipes DP) (1990) CAST and beyond. Implications of the Cardiac Arrhythmia Suppression Trial. Eur Heart J 11:194–199; Circulation 81: 1123–1127Google Scholar
  3. 3.
    Burkart F, Pfisterer M, Kiowski W, Follath F, Burckhardt D (1990) Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival ( BASIS ). J Am Coll Cardiol 16: 1711–1718PubMedCrossRefGoogle Scholar
  4. 4.
    Ceremuzynski Y, Kleczar E, Krzeminska-Pakula M, Kuch J, Nartowicz E, Smielak-Korombel J, Dyduszynski A, Maciejewicz J, Zaleska T, Lazarczyk-Kedzia E, Motyka J, Paczkowska B, Sczaniecka O, Yusuf S (1992) Effect of amiodarone on mortality after myocardial infarction: a double-blind, placebo-controlled, pilot study. J Am Coll Cardiol 20: 1056–1062PubMedCrossRefGoogle Scholar
  5. 5.
    Schwartz PJ, Camm AJ, Frangin G, Janse MJ, Julian DG, Simon P, on behalf of the EMIAT Investigators (1994) Does amiodarone reduce sudden death and cardiac mortality after myocardial infarction? The European Myocardial Infarct Amiodarone Trial ( EMIAT ). Eur Heart J 15: 620–624PubMedGoogle Scholar
  6. 6.
    Cairns JA, Connolly SJ, Gent M, Roberts R (1991) Post-myocardial infarction mortality in patients with ventricular premature depolarizations. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Pilot Study. Circulation 84: 550–557PubMedGoogle Scholar
  7. 7.
    Task Force of the Working Group on Arrhythmias of the European Society of Cardiology (Bigger JT Jr, Breithardt G, Brown AM, Camm AJ, Carmeliet E, Fozzard HA, Hoffman BF, Janse MJ, Lazzara R, Mugelli A, Myerburg RJ, Roden DM, Rosen MR, Schwartz PJ, Strauss HC, Woosley RL, Zaza A) (1991) The Sicilian Gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Eur Heart J 12: 1112–1131 and Circulation 84: 1831–1851Google Scholar
  8. 8.
    Schwartz Pt, Zaza A (1992) The “Sicilian Gambit” revisited. Theory and practice. Eur Heart J 13 [Suppl F]: 23–29PubMedGoogle Scholar
  9. 9.
    Members of the Sicilian Gambit (Breithardt G, Camm At, Campbell RWF, Fozzard HA, Hoffman BF, Janse MJ, Lazzara R, Levy S, Myerburg RJ, Roden DM, Rosen MR, Schwartz PJ, Strauss HC, Waldo AL, Wit AL, Woosley RL, Zaza A, Zipes DP eds) (1994) Antiarrhythmic therapy: a pathophysiologic approach. Futura Armonk, p 337Google Scholar
  10. 10.
    Task Force of the Working Group on Arrhythmias of the European Society of Cardiology (Bigger JT Jr, Breithardt G, Camm AJ, DeMets DL, Furberg CD, Hallstrom A, Janse MJ, Julian DG, Lan KKG, Lazzara R, Marcus FI, Moss AJ, Schwartz PJ, Tijssen JGP, Waldo AL) (1994) The early termination of clinical trials: causes, consequences, and control. With special reference to trials in the field of arrhythmias and sudden death. Eur Heart J 15: 721–738 and Circulation 89: 2892–2907Google Scholar
  11. 11.
    Lynch JJ, Wilber DJ, Montgomery DG, Hsieh TM, Patterson E, Lucchesi BR (1984) Antiarrhythmic and antifibrillatory actions of the levo-and dextrorotatory isomers of sotalol. J Cardiovasc Pharmacol 6: 1132–1141PubMedGoogle Scholar
  12. 12.
    Lynch JJ, Coskey LA, Montgomery DG, Lucchesi BR (1985) Prevention of ventricular fibrillation by dextrorotatory sotalol in a conscious canine model of sudden coronary death. Am Heart J 109: 949–958PubMedCrossRefGoogle Scholar
  13. 13.
    Schwartz Pt, Billman GE, Stone HL (1984) Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death. Circulation 69: 790–800Google Scholar
  14. 14.
    Vanoli E, Hull SS Jr, Adamson PB, Foreman RD, Schwartz PJ (1995) K channel blockade in the prevention of ventricular fibrillation due to acute ischemia and enhanced sympathetic activity. J Cardiovasc Pharmacol (in press)Google Scholar
  15. 15.
    Cobbe SM, Hoffman E, Ritzenhoff A, Brachmann J, Kubler W, Senges J (1983) Action of sotalol on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs in the late postmyocardial infarction phase. Circulation 68: 865–871PubMedCrossRefGoogle Scholar
  16. 16.
    La Rovere MT, Specchia G, Mortara A, Schwartz PJ (1988) Baroreflex sensitivity, clinical correlates and cardiovascular mortality among patients with a first myocardial infarction. Circulation 78: 816–824PubMedCrossRefGoogle Scholar
  17. 17.
    Farrell TG, Odemuyiwa O, Bashir Y, Cripps TR, Malik M, Ward DE, Camm AJ (1992) Prognostic value of baroreflex sensitivity testing after acute myocardial infarction. Br Heart J 67: 129–137PubMedCrossRefGoogle Scholar
  18. 18.
    Schwartz PJ, La Rovere MT, Vanoli E (1992) Autonomic nervous system and sudden cardiac death. Circulation 85 [Suppl I]: 177 - I91Google Scholar
  19. 19.
    Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ, and the Multicenter Post-Infarction Research Group (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59: 256–262Google Scholar
  20. 20.
    Farrell TJ, Bashir Y, Cripps T, Malik M, Poloniecki J, Bennett ED, Ward DE, Camm AJ (1991) Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-average electrocardiogram. J Am Coll Cardiol 18: 687–697PubMedCrossRefGoogle Scholar
  21. 21.
    Bigger JT Jr, Schwartz PJ (1994) Markers of vagal activity and the prediction of cardiac death after myocardial infarction. In: Levy MN, Schwartz PJ (eds) Vagal control of the heart: experimental basis and clinical implications. Futura, Armonk, pp 419–432Google Scholar
  22. 22.
    Sanguinetti MC, Jurkiewicz NK (1990) Two components of cardiac delayed rectifier K+ current. J Gen Physiol 96: 195–215PubMedCrossRefGoogle Scholar
  23. 23.
    Sanguinetti MC, Jurkiewicz NK, Siegl PKS (1991) Isoproterenol antagonizes prolongation of refractory period by the class III antiarrhythmic agent E-4031 in guinea pig myocytes. Circ Res 68: 77–84PubMedGoogle Scholar
  24. 24.
    Vanoli E, Priori SG, Nakagawa H, Hirao K, Napolitano C, Diehl L, Lazzara R, Schwartz PJ (1995) Sympathetic activation, ventricular repolarization and I, blockade: implications for the antifibrillatory efficacy of K- channel blockers. J Am Coll Cardiol 25: 1609–1614PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 1996

Authors and Affiliations

  • P. J. Schwartz
    • 1
    • 2
  1. 1.Cattedra di Cardiologia Policlinico San Matteo IRCCSUniversità degli Studi di PaviaPaviaItaly
  2. 2.Istituto di Clinica Medica Generale e Terapia MedicaUniversità degli StudiMilanItaly

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