Copyright © 2000 by the European Society of Cardiology.
Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials
revised October 22, 2000; accepted October 4, 2000
Abstract
Aims Three randomized trials of implantable cardioverter defibrillator (ICD) therapy vs medical treatment for the prevention of death in survivors of ventricular fibrillation or sustained ventricular tachycardia have been reported with what might appear to be different results. The present analysis was performed to obtain the most precise estimate of the efficacy of the ICD, compared to amiodarone, for prolonging survival in patients with malignant ventricular arrhythmia.
Methods and Results Individual patient data from the Antiarrhythmics vs Implantable Defibrillator (AVID) study, the Cardiac Arrest Study Hamburg (CASH) and the Canadian Implantable Defibrillator Study (CIDS) were merged into a master database according to a pre-specified protocol. Proportional hazard modelling of individual patient data was used to estimate hazard ratios and to investigate subgroup interactions. Fixed effect meta-analysis techniques were also used to evaluate treatment effects and to assess heterogeneity across studies. The classic fixed effects meta-analysis showed that the estimates of ICD benefit from the three studies were consistent with each other (P heterogeneity=0·306). It also showed a significant reduction in death from any cause with the ICD; with a summary hazard ratio (ICD:amiodarone) of 0·72 (95% confidence interval 0·60, 0·87;P=0·0006). For the outcome of arrhythmic death, the hazard ratio was 0·50 (95% confidence interval 0·37, 0·67;P<0·0001). Survival was extended by a mean of 4·4 months by the ICD over a follow-up period of 6 years. Patients with left ventricular ejection fraction 
35% derived significantly more benefit from ICD therapy than those with better preserved left ventricular function. Patients treated before the availability of non-thoracotomy ICD implants derived significantly less benefit from ICD therapy than those treated in the non-thoracotomy era.
Conclusion Results from the three trials of the ICD vs amiodarone are consistent with each other. There is a 28% reduction in the relative risk of death with the ICD that is due almost entirely to a 50% reduction in arrhythmic death.
Key Words: Amiodarone, implantable cardioverter defibrillator, meta-analysis, cardiac arrest, ventricular tachycardia
f1 Correspondence: Stuart J. Connolly, MD, Hamilton Health Sciences Corporation, Hamilton General Site, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada.
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D. R. Davis and A. S.L. Tang Implantable cardioverter defibrillators: therapy against Canada's leading killer Can. Med. Assoc. J., October 26, 2004; 171(9): 1037 - 1038. [Full Text] [PDF]
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P. Dorian, P. Bogaty, C. E. Buller, B. J. O'Neill, and P. W. Armstrong Applying the new STEMI guidelines: 2. Disturbances of cardiac rhythm after ST-segment elevation myocardial infarction Can. Med. Assoc. J., October 26, 2004; 171(9): 1042 - 1044. [Full Text] [PDF]
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R. Parkash, A. Tang, G. Wells, J. Blackburn, I. Stiell, C. Simpson, P. Dorian, R. Yee, D. Cameron, S. Connolly, et al. Use of implantable cardioverter defibrillators after out-of-hospital cardiac arrest: a prospective follow-up study Can. Med. Assoc. J., October 26, 2004; 171(9): 1053 - 1056. [Abstract] [Full Text] [PDF]
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H. J. Wellens Randomized Clinical Trials: How Long Should They Last? Circulation, July 13, 2004; 110(2): 107 - 108. [Full Text] [PDF]
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F. Bokhari, D. Newman, M. Greene, V. Korley, I. Mangat, and P. Dorian Long-Term Comparison of the Implantable Cardioverter Defibrillator Versus Amiodarone: Eleven-Year Follow-Up of a Subset of Patients in the Canadian Implantable Defibrillator Study (CIDS) Circulation, July 13, 2004; 110(2): 112 - 116. [Abstract] [Full Text] [PDF]
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C. D. Swerdlow Reappraisal of implant testing of implantable cardioverter defibrillators J. Am. Coll. Cardiol., July 7, 2004; 44(1): 92 - 94. [Full Text] [PDF]
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R. Cappato, S. Boczor, K.-H. Kuck, and on behalf of the CASH Investigators Response to programmed ventricular stimulation and clinical outcome in cardiac arrest survivors receiving randomised assignment to implantable cardioverter defibrillator or antiarrhythmic drug therapy Eur. Heart J., April 2, 2004; 25(8): 642 - 649. [Abstract] [Full Text] [PDF]
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A. Quesada, J.ús Almendral, F. Arribas, R. Ricci, C. Wolpert, P. Adragao, E. Cobo, X. Navarro, and on behalf DATAS investigators The DATAS rationale and design: a controlled, randomized trial to assess the clinical benefit of dual chamber (DDED) defibrillator Europace, January 1, 2004; 6(2): 142 - 150. [Abstract] [Full Text] [PDF]
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E.W. Lau, M.J. Griffith, R.K. Pathmanathan, G.A. Ng, M.M. Clune, J. Cooper, H.J. Marshall, P.R. Forsey, P.J. Stafford, R.G. Gray, et al. The midlands trial of empirical amiodarone versus electrophysiology-guided interventions and implantable cardioverter-defibrillators (MAVERIC): a multi-centre prospective randomised clinical trial on the secondary prevention of sudden cardiac death Europace, January 1, 2004; 6(4): 257 - 266. [Abstract] [Full Text] [PDF]
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J. P. DiMarco Implantable Cardioverter-Defibrillators N. Engl. J. Med., November 6, 2003; 349(19): 1836 - 1847. [Full Text] [PDF]
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G. Nichol, T. Valenzuela, D. Roe, L. Clark, E. Huszti, and G.A. Wells Cost Effectiveness of Defibrillation by Targeted Responders in Public Settings Circulation, August 12, 2003; 108(6): 697 - 703. [Abstract] [Full Text] [PDF]
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G. Boriani, M. Biffi, C. Martignani, C. Camanini, F. Grigioni, C. Rapezzi, and A. Branzi Cardioverter-defibrillators after MADIT-II: the balance between weight of evidence and treatment costs Eur J Heart Fail, August 1, 2003; 5(4): 419 - 425. [Abstract] [Full Text] [PDF]
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J. V. Jayachandran and D. P. Zipes Say no to primary prophylaxis with implantable cardioverter-defibrillators in asymptomatic nonischemic dilated cardiomyopathy? J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1713 - 1715. [Full Text] [PDF]
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D. S. Lee, L. D. Green, P. P. Liu, P. Dorian, D. M. Newman, F. C. Grant, J. V. Tu, and D. A. Alter Effectiveness of implantable defibrillators for preventing arrhythmic events and death: A Meta-Analysis J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1573 - 1582. [Abstract] [Full Text] [PDF]
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P. C. Deedwania The Key to Unraveling the Mystery of Mortality in Heart Failure: An Integrated Approach Circulation, April 8, 2003; 107(13): 1719 - 1721. [Full Text] [PDF]
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J. A. Ezekowitz, P. W. Armstrong, and F. A. McAlister Implantable Cardioverter Defibrillators in Primary and Secondary Prevention: A Systematic Review of Randomized, Controlled Trials Ann Intern Med, March 18, 2003; 138(6): 445 - 452. [Abstract] [Full Text] [PDF]
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M. L. Weisfeldt and L. B. Becker Resuscitation After Cardiac Arrest: A 3-Phase Time-Sensitive Model JAMA, December 18, 2002; 288(23): 3035 - 3038. [Full Text] [PDF]
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S. Yusuf and B. Pitt A Lifetime of Prevention: The Case of Heart Failure Circulation, December 10, 2002; 106(24): 2997 - 2998. [Full Text] [PDF]
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J. M Morgan PATIENTS WITH VENTRICULAR ARRHYTHMIAS: WHO SHOULD BE REFERRED TO AN ELECTROPHYSIOLOGIST? Heart, December 1, 2002; 88(5): 544 - 550. [Full Text] [PDF]
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S Z Abildstrom, C Rask-Madsen, M M Ottesen, P K Andersen, S Rosthoj, C Torp-Pedersen, and L Kober Impact of age and sex on sudden cardiovascular death following myocardial infarction Heart, December 1, 2002; 88(6): 573 - 578. [Abstract] [Full Text] [PDF]
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A. Maisel B-Type Natriuretic Peptide Levels: Diagnostic and Prognostic in Congestive Heart Failure: What's Next? Circulation, May 21, 2002; 105(20): 2328 - 2331. [Full Text] [PDF]
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R. Berger, M. Huelsman, K. Strecker, A. Bojic, P. Moser, B. Stanek, and R. Pacher B-Type Natriuretic Peptide Predicts Sudden Death in Patients With Chronic Heart Failure Circulation, May 21, 2002; 105(20): 2392 - 2397. [Abstract] [Full Text] [PDF]
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S. Nisam and J. Farre Is prophylaxis the best use of the ICD? Eur. Heart J., May 1, 2002; 23(9): 700 - 705. [Full Text] [PDF]
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J Parkes, J Bryant, and R Milne Implantable cardioverter-defibrillators in arrhythmias: a rapid and systematic review of effectiveness Heart, May 1, 2002; 87(5): 438 - 442. [Abstract] [Full Text] [PDF]
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C Stellbrink, A.-M Sinha, B Diem, A Auricchio, S Boccanelli, J Brugada, H Klein, J Morgan, L Padeletti, E Aliot, et al. Implantable card ioverter-defibrillators with or without cardiac resynchronization therapy -- multiple therapy in a single device: a review with special reference to the PACIVIAN study Eur. Heart J. Suppl., April 1, 2002; 4(suppl_D): D88 - D94. [Abstract] [PDF]
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R. Gradaus, S. Kerber, D. Bocker, H. H. Scheld, G. Breithardt, and M. C. Deng Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period Eur J Heart Fail, March 1, 2002; 4(2): 207 - 214. [Abstract] [Full Text] [PDF]
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