Are Implantable Cardioverter-Defibrillators Better Than Conventional Antiarrhythmic Drugs for Survivors of Cardiac Arrest?
1995; Lippincott Williams & Wilkins; Volume: 91; Issue: 8 Linguagem: Inglês
10.1161/01.cir.91.8.2115
ISSN1524-4539
Autores Tópico(s)Cardiac Arrhythmias and Treatments
ResumoHomeCirculationVol. 91, No. 8Are Implantable Cardioverter-Defibrillators Better Than Conventional Antiarrhythmic Drugs for Survivors of Cardiac Arrest? Free AccessResearch ArticleDownload EPUBAboutView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticleDownload EPUBAre Implantable Cardioverter-Defibrillators Better Than Conventional Antiarrhythmic Drugs for Survivors of Cardiac Arrest? Douglas P. Zipes Douglas P. ZipesDouglas P. Zipes From Krannert Institute of Cardiology and Indiana University School of Medicine, Indianapolis, Ind. Originally published15 Apr 1995https://doi.org/10.1161/01.CIR.91.8.2115Circulation. 1995;91:2115–2117Numerous studies have shown that the implantable cardioverter-defibrillator (ICD) accurately detects and successfully terminates ventricular tachyarrhythmias. In a recent report of 2834 epicardial and endocardial ICD implants in 2807 patients followed for a mean of 11.7 months, more than half of the patients had a combined total of almost 50 000 spontaneous episodes of ventricular tachyarrhythmias that were recognized and terminated by the ICD, with a success rate of about 98%. At 1 year, sudden cardiac death mortality was 1.4% in the epicardial ICD group and 0.6% in the endocardial group. The overall mortality at 1 year was 12.2% and 6.9% for the two groups, respectively, reflecting in part the greater surgical implant mortality for the epicardial (4.1%) compared with the endocardial (0.74%) systems. Complications requiring an invasive intervention totaled 18.9% for the endocardial implants and 9.2% for the epicardial implants.1 Thus, it becomes amply clear that the ICD effectively performs the functions for which it was created. Data such as these have encouraged many physicians to proceed rapidly to implantation of an ICD in the cardiac arrest survivor rather than spend time searching for a potentially more elusive therapeutic goal, that of an effective antiarrhythmic drug. Despite these facts (and the "logical" extension that ICDs must save lives if they effectively terminate ventricular tachyarrhythmias), several reports234 have cautioned against a precipitous embrace of ICDs because the ICD effect on total mortality, particularly when compared against antiarrhythmic agents, has not been established in a rigorous fashion, that is, in a prospective, randomized clinical trial. In fact, as I stated in a recent editorial, "Until we directly randomize the ICD against the best medical management, we will not know which therapy is best in general or for a specific patient group."5 Randomization eliminates the risk of differences due to bias and if sufficient numbers are enrolled the chance differences between the treatment groups. Three large trials now in progress are attempting to answer the question of superiority between device and drug for the patient with a life-threatening ventricular tachyarrhythmia and include the Cardiac Arrest Study Hamburg (CASH),6 the Canadian Implantable Defibrillator Study (CIDS),7 and the Antiarrhythmics Versus Implantable Defibrillators (AVID) investigation,8 supported by the National Heart, Lung, and Blood Institute. A total of more than 2000 patients will be randomized in these three trials, and they should be able to answer the question of which is the better treatment. Preliminary data from these trials are interesting. The CASH study began with four arms, randomizing patients among propafenone, amiodarone, metoprolol, and an ICD. The propafenone arm was stopped because of excess mortality, but the other therapies continue because there appear to be no significant differences in total mortality among the three groups.6 There are fewer sudden deaths in the ICD group, but the overall mortality is the same as in the other two groups. CIDS randomizes between amiodarone and an ICD and has increased the size of the study from 400 to 500 patients and has extended the completion date from January 1, 1996, to January 1, 1997. The data safety and monitoring board has found no reason to stop the study, and the investigators may increase the enrollment still further to 650 patients. Interestingly, addition of amiodarone to ICD therapy has occurred in 18% of patients, while crossover from amiodarone to an ICD is 9.0% (Stuart J. Connolly, personal communication). In AVID, the preliminary feasibility study that randomized 200 patients to amiodarone (a small number received sotalol) or an ICD has been completed, and another 150 patients have been randomized into the main portion of the study. To date, the number of crossovers between amiodarone and an ICD have been small and equal in both directions.8Thus, these preliminary data from three large randomized trials raise the possibility that while the ICD may reduce sudden death mortality, there may be no difference in total mortality between amiodarone (and metoprolol in CASH) and an ICD. If true, one could explain the minimal impact of an ICD on total mortality by the operative mortality incurred with thoracotomy systems, now avoided with the use of transvenous systems, or the possibility that prevention of sudden death only slightly delays death from other causes. However, before making any conclusions, it must be emphasized that these studies are ongoing and that preliminary mortality data are available only for CASH.Now we come to the present study,9 the first to be published in which survivors of cardiac arrest due to late postinfarction ventricular tachycardia or fibrillation were randomized to an ICD or antiarrhythmic agent. Conventional antiarrhythmic drugs were used, and only two patients ended up receiving amiodarone. Drug efficacy was established by the results of electrophysiological testing. Although the study was intended to be a test of cost-effectiveness, the authors analyzed the results for outcome and concluded that early defibrillator implantation was associated with a significantly lower number of main outcome events including death, prolonged syncope with cardiac arrest, and end-stage pump failure necessitating cardiac transplantation. Furthermore, they found better exercise tolerance, shorter hospitalization, lower number of invasive procedures, and less antiarrhythmic therapy changes in the early ICD group. Drug-treated patients were likely to end up with an ICD, and those who remained on drugs as sole therapy had a high risk of death regardless of efficacy assessment. These conclusions were based on the fact that, of the 29 patients who received an ICD, there were only 4 deaths. Twenty of 31 patients randomized to drugs failed tests of drug efficacy (arrhythmia inducibility at electrophysiological study) and received map-guided surgery (6 patients, of whom 1 died, 1 had cardiac transplantation, and 1 had an ICD implantation) or ICD implantation (14). Of the remaining 11 who received drugs alone, 2 died in the hospital before being retested, 5 subsequently died, and 1 survived cardiac arrest. Therefore, 16 patients who initially received conventional drugs ended up with an ICD, and 3 subsequently died to give a mortality of 11 (35%) in the drug group versus 13% for the ICD group. These appear to be quite impressive differences, leading the authors to conclude that the ICD is to be preferred over conventional drugs for survivors of cardiac arrest due to old myocardial infarction. We need to ask whether this conclusion is valid, and if so, whether it can be extrapolated to all antiarrhythmic drugs. This is a well-performed study, but there are some problems with it, as acknowledged by the authors. First, the number of patients (60) is very small and was limited by the size of the grant the authors received to do the study. Thus, regardless of the statistical outcomes, even with the appropriate caution by the authors that confidence limits rather than P values be used as the best estimate of outcome, one must accept the data cautiously. Second, class I (Vaughan Williams) antiarrhythmic drugs or sotalol was used to treat all except 2 patients who were randomized to the drug arm. One of these 2 patients received amiodarone and the other received amiodarone plus quinidine. Leaving amiodarone as the last drug is understandable when using an electrophysiologically guided approach and considering the fact that the study began in April 1989. Even so, most of these patients did not receive a trial with amiodarone before being switched to other therapy. Today, sufficient data exist from controlled and noncontrolled studies101112131415 to make a good case for using empiric amiodarone, noting that it is not particularly effective in preventing electrically induced arrhythmias but does appear to have a favorable impact on spontaneous arrhythmias and death. The class I drugs the authors chose to use are known to have either an adverse effect on mortality or no proven benefit for patients with ventricular arrhythmias after myocardial infarction.161718 That is the reason amiodarone was selected for use in CASH, CIDS, and AVID. Also, given the low success rate of any antiarrhythmic drug in preventing arrhythmia inducibility by electrophysiological testing,19 the study from the beginning stacks the deck against drugs compared with ICDs, either in improving outcome, based on an intention-to-treat analysis, or reducing cost. Finally, 8 of the 29 patients who had an ICD implanted also had coronary revascularization, compared with only 3 of the conventionally treated group. What can we conclude from this report? First, the authors are to be complimented for leading the way with a randomized investigation of this type. It took courage and foresight to start this project in 1989. Second, despite the deficiencies, I think we can say that the ICD is superior to class I antiarrhythmic drugs for patients with an old myocardial infarction who have survived a cardiac arrest. I make that conclusion based on data from the present study9 and the impressive survival statistics from the transvenous ICD lead system1 (albeit not a randomized trial) versus no published data showing an improvement in mortality with class I drugs.161718 The results are too lopsided not to believe. However, it is important to stress that, as far as I am concerned, it still has not been shown whether an ICD is better than amiodarone. That conclusion awaits completion of CASH, CIDS, and AVID. The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. Dr Zipes is supported in part by the Herman C. Krannert Fund, by grant 1P50-HL-52323 from the National Heart, Lung, and Blood Institutes of the National Institutes of Health, and by the US Public Health Service. The author thanks Alfred P. Hallstrom, PhD, for helpful comments. FootnotesCorrespondence to Douglas P. Zipes, MD, Krannert Institute of Cardiology, 1111 W 10th St, Indianapolis, IN 46202-4800. References 1 Zipes DP, Roberts D, PCD Investigators. Results of the world-wide study of the implantable pacemaker, cardioverter-defibrillator: a comparison of epicardial and endocardial lead systems. Circulation. In press. Google Scholar2 Connolly SJ, Yusuf S. Evaluation of the implantable cardioverter defibrillator in survivors of cardiac arrest: the need for randomized trials. Am J Cardiol.1992; 69:959-962. CrossrefMedlineGoogle Scholar3 Epstein AE. AVID necessity. PACE Pacing Clin Electrophysiol.1993; 16:1773-1775. CrossrefMedlineGoogle Scholar4 Green HL. Antiarrhythmic drugs versus implantable defibrillators: the need for a randomized controlled study. Am Heart J. 1994; 127:1171-1178. Google Scholar5 Zipes DP. Implantable cardioverter-defibrillator: lifesaver or a device looking for a disease? Circulation.1994; 89:2934-2936. CrossrefMedlineGoogle Scholar6 Siebels J, Kuck KH. Implantable cardioverter defibrillator compared with antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac Arrest Study Hamburg). Am Heart J.1994; 127:1139-1144. CrossrefMedlineGoogle Scholar7 Connolly SJ, Jent M, Roberts RS, Dorian P, Green MS, Klein GJ, Mitchell LB, Sheldon RS, Roy D. Canadian Implantation Defibrillator Study (CIDS): study design and organization. Am J Cardiol.1993; 72:103F-108F. CrossrefMedlineGoogle Scholar8 AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators (AVID): rationale, design and methods. Am J Cardiol. In press. Google Scholar9 Wever EFD, Hauer RNW, van Capelle FJL, Tijssen JGP, Crijns HJGM, Algra A, Wiesfeld ACP, Bakker PFA, de Medina EOR. Randomized study of implantable defibrillator as first-choice therapy versus conventional strategy in postinfarct sudden death survivors. Circulation.1995; 91:2195-2203. CrossrefMedlineGoogle Scholar10 Herre J, Suave M, Malone P, Griffin JC, Helmy I, Langberg JJ, Goldberg H, Scheinman MM. Long term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. J Am Coll Cardiol.1989; 13:442-449. CrossrefMedlineGoogle Scholar11 Weinberg BA, Miles WM, Klein LS, Bolander JE, Dusman RE, Stanton MS, Heger JJ, Langefeld C, Zipes DP. Five-year follow-up of 589 patients treated with amiodarone. Am Heart J.1993; 125:109-120. CrossrefMedlineGoogle Scholar12 Burkart F, Pfisterer M, Kiowski W, Follath F, Burckhardt D, Jardi H. Effective antiarrhythmic therapy on mortality in survivors of myocardial infarction with symptomatic complex ventricular arrhythmias: Basal Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol.1990; 16:1711-1718. CrossrefMedlineGoogle Scholar13 Ceremuzynski L, Kleczor E, Kreminska-Pakula M. Effective amiodarone on mortality after myocardial infarction: a double blinded placebo-controlled pilot study. J Am Coll Cardiol.1992; 20:1056-1062. CrossrefMedlineGoogle Scholar14 CASCADE Investigators. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the CASCADE Study). Am J Cardiol.1993; 72:280-287. CrossrefMedlineGoogle Scholar15 Doval HC, Nul DR, Grancelli HO. Randomized trial of low-dose amiodarone in severe congestive heart failure: Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA). Lancet.1994; 344:493-498. CrossrefMedlineGoogle Scholar16 Teo KK, Yusuf S, Furberg CD. Effects of prophylatic antiarrhythmic drug therapy in acute myocardial infarction: an overview of results from 22 randomized controlled trials. J Am Coll Cardiol.1993; 270:1589-1595. Google Scholar17 Cardiac Arrhythmia Suppression Trial Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. (CAST I). N Engl J Med.1989; 321:406-412. CrossrefMedlineGoogle Scholar18 Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med.1992; 327:227-235. CrossrefMedlineGoogle Scholar19 Ward DE, Camm AJ. Dangerous ventricular arrhythmias: can we predict drug efficacy? N Engl J Med.1993; 329:498-499. CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Robinson M, Epstein A and Callans D (2011) Secondary Prevention in Heart Failure, Heart Failure Clinics, 10.1016/j.hfc.2010.12.002, 7:2, (185-194), Online publication date: 1-Apr-2011. Fatkin D, Seidman J and Seidman C (2007) Hypertrophic Cardiomyopathy Cardiovascular Medicine, 10.1007/978-1-84628-715-2_59, (1261-1284), . Hohnloser S (1999) Implantable devices versus antiarrhythmic drug therapy in recurrent ventricular tachycardia and ventricular fibrillation, The American Journal of Cardiology, 10.1016/S0002-9149(99)00702-X, 84:9, (56-62), Online publication date: 1-Nov-1999. Gilbert-Barness E and Barness L (2019) Nonmalformative Cardiovascular Pathology in Infants and Children, Pediatric and Developmental Pathology, 10.1007/s100249900157, 2:6, (499-530), Online publication date: 1-Nov-1999. Zaidan J (1999) Implantable cardioverter-defibrillators, Journal of Cardiothoracic and Vascular Anesthesia, 10.1016/S1053-0770(99)90226-4, 13:4, (475-483), Online publication date: 1-Aug-1999. NACCARELLLI G, WOLBRETTE D, DELL'ORFANO J, PATEL H and LUCK J (1998) A Decade of Clinical Trial Developments in Postmyocardial Infarction, Congestive Heart Failure, and Sustained Ventricular Tachyarrhythmia Patients: From CAST to AVID and Beyond, Journal of Cardiovascular Electrophysiology, 10.1111/j.1540-8167.1998.tb00127.x, 9:8, (864-891), Online publication date: 1-Aug-1998. CANNOM D (1998) AVID and Beyond: Lessons Learned, Journal of Interventional Cardiology, 10.1111/j.1540-8183.1998.tb00122.x, 11:3, (217-226), Online publication date: 1-Jun-1998. Haverkamp W, Eckardt L, Borggrefe M and Breithardt G (1997) Drugs Versus Devices in Controlling Ventricular Tachycardia, Ventricular Fibrillation, and Recurrent Cardiac Arrest, The American Journal of Cardiology, 10.1016/S0002-9149(97)00715-7, 80:8, (67G-73G), Online publication date: 1-Oct-1997. Singh B (1997) Amiodarone: The expanding antiarrhythmic role and how to follow a patient on chronic therapy, Clinical Cardiology, 10.1002/clc.4960200706, 20:7, (608-618), Online publication date: 1-Jul-1997. Spirito P, Seidman C, McKenna W and Maron B (1997) The Management of Hypertrophic Cardiomyopathy, New England Journal of Medicine, 10.1056/NEJM199703133361107, 336:11, (775-785), Online publication date: 13-Mar-1997. Nielsen J, Mortensen P and Pedersen A (2009) Long-term Follow-up of Patients Treated with Implantable Cardioverter Defibrillators in a Danish Centre: Occurrence of ICD Therapy and Patient Survival, Scandinavian Cardiovascular Journal, 10.3109/14017439709058085, 31:3, (151-156), Online publication date: 1-Jan-1997. (1996) 心室性不整脈 : 非薬物療法 : 頻脈性不整脈の成因と治療 : 第24回循環器教育セッション, Journal of JCS Cardiologists, 10.1253/jjcsc.4.2_315, 4:2, (315-321), Online publication date: 11-Oct-1996. Singh B (2016) Amiodarone and Homogeneity of Ventricular Repolarization and Refractoriness, Journal of Cardiovascular Pharmacology and Therapeutics, 10.1177/107424849600100401, 1:4, (265-270), Online publication date: 1-Oct-1996. Singh B (1996) Antiarrhythmic Actions of Amiodarone: A Profile of a Paradoxical Agent, The American Journal of Cardiology, 10.1016/S0002-9149(96)00452-3, 78:4, (41-53), Online publication date: 1-Aug-1996. Singh B (1996) The Coming of Age of the Class III Antiarrhythmic Principle: Retrospective and Future Trends, The American Journal of Cardiology, 10.1016/S0002-9149(96)00449-3, 78:4, (17-27), Online publication date: 1-Aug-1996. Saksena S, Breithardt G, Dorian P, Greene H, Madan N and Block M (1996) Nonpharmacological therapy for malignant ventricular arrhythmias: Implantable defibrillator trials, Progress in Cardiovascular Diseases, 10.1016/S0033-0620(96)80007-7, 38:6, (429-444), Online publication date: 1-May-1996. Singh B (2016) Editorial: Rise and Fall of Guided Antiarrhythmic Therapy for Ventricular Tachycardia and Fibrillation, Journal of Cardiovascular Pharmacology and Therapeutics, 10.1177/107424849600100201, 1:2, (89-94), Online publication date: 1-Apr-1996. Ferguson T, Ferguson C, Crites K and Crimmins-Reda P (1996) The additional hospital costs generated in the management of complications of pacemaker and defibrillator implantations, The Journal of Thoracic and Cardiovascular Surgery, 10.1016/S0022-5223(96)70334-3, 111:4, (742-752), Online publication date: 1-Apr-1996. Josephson M and Nisam S (1996) Prospective trials of implantable cardioverter delibrillators versus drugs: Are they addressing the right question?, The American Journal of Cardiology, 10.1016/S0002-9149(97)89182-5, 77:10, (859-863), Online publication date: 1-Apr-1996. Singh B (2016) Antiarrhythmic Therapy of Ventricular Arrhythmias: The Contemporary Dilemma, Journal of Cardiovascular Pharmacology and Therapeutics, 10.1177/107424849600100102, 1:1, (3-7), Online publication date: 1-Jan-1996. Proclemer A, Facchin D, Miani D, Vanuzzo D and Feruglio G (1996) Beta Blockers, Sotalol, or Amiodarone for the Treatment of Malignant Ventricular Arrhythmias? Cardiac Arrhythmias 1995, 10.1007/978-88-470-2223-2_5, (23-30), . Bellocci F, Pelargonio G, Bendini M, Intini A, Affinito V, Sacchetti O, Bruni G, Montenero A and Zecchi P (1996) Implantable Cardioverter Defibrillator: A Therapy for Everyone or for Selected Patients? Cardiac Arrhythmias 1995, 10.1007/978-88-470-2223-2_15, (86-90), . SINGH B (1995) Expanding Indications for the Use of Class III Agents in Patients at High Risk for Sudden Death, Journal of Cardiovascular Electrophysiology, 10.1111/j.1540-8167.1995.tb00365.x, 6:10, (887-900), Online publication date: 1-Oct-1995. April 15, 1995Vol 91, Issue 8 Advertisement Article InformationMetrics Copyright © 1995 by American Heart Associationhttps://doi.org/10.1161/01.CIR.91.8.2115 Manuscript receivedFebruary 1, 1995Manuscript acceptedFebruary 1, 1995Originally publishedApril 15, 1995 KeywordsEditorialstachyarrhythmiasantiarrhythmia agents Advertisement
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