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. 1992 Jun;67(6):491–497. doi: 10.1136/hrt.67.6.491

Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms.

M Zehender 1, S Hohnloser 1, A Geibel 1, A Furtwängler 1, M Olschewski 1, T Meinertz 1, H Just 1
PMCID: PMC1024894  PMID: 1622701

Abstract

OBJECTIVE--To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile. DESIGNS--Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year. PATIENTS--One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months. ANALYSIS--Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone. MEASUREMENTS AND MAIN RESULTS--Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment. CONCLUSIONS--A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment.

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Selected References

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  1. Brodsky M. A., Allen B. J., Abate D., Henry W. L. Propafenone therapy for ventricular tachycardia in the setting of congestive heart failure. Am Heart J. 1985 Oct;110(4):794–799. doi: 10.1016/0002-8703(85)90459-4. [DOI] [PubMed] [Google Scholar]
  2. Delgado C., Tamargo J., Tejerina T. Electrophysiological effects of propafenone in untreated and propafenone-pretreated guinea-pig atrial and ventricular muscle fibres. Br J Pharmacol. 1985 Dec;86(4):765–775. doi: 10.1111/j.1476-5381.1985.tb11098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dinh H. A., Murphy M. L., Baker B. J., deSoyza N., Franciosa J. A. Efficacy of propafenone compared with quinidine in chronic ventricular arrhythmias. Am J Cardiol. 1985 Jun 1;55(13 Pt 1):1520–1524. doi: 10.1016/0002-9149(85)90965-8. [DOI] [PubMed] [Google Scholar]
  4. Dinh H., Baker B. J., de Soyza N., Murphy M. L. Sustained therapeutic efficacy and safety of oral propafenone for treatment of chronic ventricular arrhythmias: a 2-year experience. Am Heart J. 1988 Jan;115(1 Pt 1):92–96. doi: 10.1016/0002-8703(88)90522-4. [DOI] [PubMed] [Google Scholar]
  5. Dukes I. D., Vaughan Williams E. M. The multiple modes of action of propafenone. Eur Heart J. 1984 Feb;5(2):115–125. doi: 10.1093/oxfordjournals.eurheartj.a061621. [DOI] [PubMed] [Google Scholar]
  6. Fauchier J. P., Cosnay P., Rouesnel P., Moquet B., Huguet R., Wajman A. Etude comparative de l'efficacité de la propafénone et de l'amiodarone dans le traitement des extrasystoles ventriculaires chroniques. Arch Mal Coeur Vaiss. 1986 Sep;79(10):1495–1505. [PubMed] [Google Scholar]
  7. Funck-Brentano C., Kroemer H. K., Lee J. T., Roden D. M. Propafenone. N Engl J Med. 1990 Feb 22;322(8):518–525. doi: 10.1056/NEJM199002223220806. [DOI] [PubMed] [Google Scholar]
  8. Gebhardt A., Schmuderer R., Hilpert P. Vergleichende Untersuchungen von Tocainid und Propafenon zur Behandlung von ventrikulären Arrhythmien. Arzneimittelforschung. 1984;34(3):303–306. [PubMed] [Google Scholar]
  9. Geibel A., Meinertz T., Zehender M., Vitak J., Hohnloser S., Kunz-Fritze A., Just H. Antiarrhythmic efficacy and tolerance of oral propafenone in patients with frequent ventricular arrhythmias: experience of a multicentre study. Eur Heart J. 1989 Sep;10 (Suppl E):81–87. doi: 10.1093/eurheartj/10.suppl_e.81. [DOI] [PubMed] [Google Scholar]
  10. Graboys T. B., Lown B., Podrid P. J., DeSilva R. Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs. Am J Cardiol. 1982 Sep;50(3):437–443. doi: 10.1016/0002-9149(82)90307-1. [DOI] [PubMed] [Google Scholar]
  11. Hammill S. C., Sorenson P. B., Wood D. L., Sugrue D. D., Osborn M. J., Gersh B. J., Holmes D. R., Jr Propafenone for the treatment of refractory complex ventricular ectopic activity. Mayo Clin Proc. 1986 Feb;61(2):98–103. doi: 10.1016/s0025-6196(12)65194-5. [DOI] [PubMed] [Google Scholar]
  12. Harron D. W., Brogden R. N. Propafenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. Drugs. 1987 Dec;34(6):617–647. doi: 10.2165/00003495-198734060-00001. [DOI] [PubMed] [Google Scholar]
  13. Hill M. R., Gotz V. P., Harman E., McLeod I., Hendeles L. Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug. Comparison of spirometry with methacholine challenge. Chest. 1986 Nov;90(5):698–702. doi: 10.1378/chest.90.5.698. [DOI] [PubMed] [Google Scholar]
  14. Horowitz L. N. Ventricular arrhythmias: control of therapy by Holter monitoring. Eur Heart J. 1989 Sep;10 (Suppl E):53–60. doi: 10.1093/eurheartj/10.suppl_e.53. [DOI] [PubMed] [Google Scholar]
  15. Härtel G. Efficacy of oral propafenone in chronic ventricular arrhythmias: a placebo controlled cross-over exercise study. Eur Heart J. 1985 Feb;6(2):123–129. doi: 10.1093/oxfordjournals.eurheartj.a061826. [DOI] [PubMed] [Google Scholar]
  16. Klempt H. W., Nayebagha A., Fabry E. Antiarrhythmische Wirksamkeit von Mexiletin, Propafenon und Flecainid bei der ventrikulären Extrasystolie. Eine vergleichend Untersuchung bei Patienten mit Zustand nach Herzinfarkt. Z Kardiol. 1982 May;71(5):340–349. [PubMed] [Google Scholar]
  17. Ledda F., Mantelli L., Manzini S., Amerini S., Mugelli A. Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations. J Cardiovasc Pharmacol. 1981 Nov-Dec;3(6):1162–1173. doi: 10.1097/00005344-198111000-00002. [DOI] [PubMed] [Google Scholar]
  18. Malfatto G., Zaza A., Forster M., Sodowick B., Danilo P., Jr, Rosen M. R. Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone. J Pharmacol Exp Ther. 1988 Aug;246(2):419–426. [PubMed] [Google Scholar]
  19. McLeod A. A., Stiles G. L., Shand D. G. Demonstration of beta adrenoceptor blockade by propafenone hydrochloride: clinical pharmacologic, radioligand binding and adenylate cyclase activation studies. J Pharmacol Exp Ther. 1984 Feb;228(2):461–466. [PubMed] [Google Scholar]
  20. Michel D. Propafenon auf dem Weg in die neue Welt. Profil des Antiarrhythmikums. Fortschr Med. 1989 Apr 30;107(13):81–81. [PubMed] [Google Scholar]
  21. Morganroth J., Michelson E. L., Horowitz L. N., Josephson M. E., Pearlman A. S., Dunkman W. B. Limitations of routine long-term electrocardiographic monitoring to assess ventricular ectopic frequency. Circulation. 1978 Sep;58(3 Pt 1):408–414. doi: 10.1161/01.cir.58.3.408. [DOI] [PubMed] [Google Scholar]
  22. Müller-Peltzer H., Greger G., Neugebauer G., Hollmann M. Beta-blocking and electrophysiological effects of propafenone in volunteers. Eur J Clin Pharmacol. 1983;25(6):831–833. doi: 10.1007/BF00542530. [DOI] [PubMed] [Google Scholar]
  23. Podrid P. J. Aggravation of arrhythmia: a complication of antiarrhythmic drug therapy. Eur Heart J. 1989 Sep;10 (Suppl E):66–72. doi: 10.1093/eurheartj/10.suppl_e.66. [DOI] [PubMed] [Google Scholar]
  24. Podrid P. J., Lown B. Propafenone: a new agent for ventricular arrhythmia. J Am Coll Cardiol. 1984 Jul;4(1):117–125. doi: 10.1016/s0735-1097(84)80328-9. [DOI] [PubMed] [Google Scholar]
  25. Rabkin S. W., Boroomand-Rashti K., McKinnon J., Rotem C. E. Comparison of propafenone and disopyramide in the treatment of ventricular premature complexes: a randomized double blind crossover placebo controlled trial. Can J Cardiol. 1987 Apr;3(3):105–110. [PubMed] [Google Scholar]
  26. Salerno D. M., Granrud G., Sharkey P., Asinger R., Hodges M. A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes. Am J Cardiol. 1984 Jan 1;53(1):77–83. doi: 10.1016/0002-9149(84)90687-8. [DOI] [PubMed] [Google Scholar]
  27. Siddoway L. A., Thompson K. A., McAllister C. B., Wang T., Wilkinson G. R., Roden D. M., Woosley R. L. Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation. 1987 Apr;75(4):785–791. doi: 10.1161/01.cir.75.4.785. [DOI] [PubMed] [Google Scholar]
  28. Singh B. N., Kaplinsky E., Kirsten E., Guerrero J. Effects of propafenone on ventricular arrhythmias: double-blind, parallel, randomized, placebo-controlled dose-ranging study. Am Heart J. 1988 Dec;116(6 Pt 1):1542–1551. doi: 10.1016/0002-8703(88)90741-7. [DOI] [PubMed] [Google Scholar]
  29. Thompson K. A., Iansmith D. H., Siddoway L. A., Woosley R. L., Roden D. M. Potent electrophysiologic effects of the major metabolites of propafenone in canine Purkinje fibers. J Pharmacol Exp Ther. 1988 Mar;244(3):950–955. [PubMed] [Google Scholar]
  30. Tobis J., Nalcioglu O., Johnston W. D., Qu L., Reese T., Sato D., Roeck W., Montelli S., Henry W. L. Videodensitometric determination of minimum coronary artery luminal diameter before and after angioplasty. Am J Cardiol. 1987 Jan 1;59(1):38–44. doi: 10.1016/s0002-9149(87)80065-6. [DOI] [PubMed] [Google Scholar]
  31. de Soyza N., Terry L., Murphy M. L., Thompson C. H., Doherty J. E., Sakhaii M., Dinh H. Effect of propafenone in patients with stable ventricular arrhythmias. Am Heart J. 1984 Aug;108(2):285–289. doi: 10.1016/0002-8703(84)90613-6. [DOI] [PubMed] [Google Scholar]
  32. von Philipsborn G., Gries J., Hofmann H. P., Kreiskott H., Kretzschmar R., Müller C. D., Raschack M., Teschendorf H. J. Pharmacological studies on propafenone and its main metabolite 5-hydroxypropafenone. Arzneimittelforschung. 1984;34(11):1489–1497. [PubMed] [Google Scholar]

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