This Article Full Text Full Text (PDF) All Versions of this Article: 110/24/3646    most recent 01.CIR.0000149240.98971.A8v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dorian, P. Search for Related Content PubMed PubMed Citation Articles by Dorian, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Cardiovascular Pharmacology Ablation/ICD/surgery Arrhythmias, clinical electrophysiology, drugs Related Article

(Circulation. 2004;110:3646-3654.)
© 2004 American Heart Association, Inc.

Late-Breaking Clinical Trials

Placebo-Controlled, Randomized Clinical Trial of Azimilide for Prevention of Ventricular Tachyarrhythmias in Patients With an Implantable Cardioverter Defibrillator

Paul Dorian, MD; Martin Borggrefe, MD; Hussein R. Al-Khalidi, PhD; Stefan H. Hohnloser, MD; Jose M. Brum, MD; Daljit S. Tatla, PhD; Johannes Brachmann, MD; Robert J. Myerburg, MD; David S. Cannom, MD; Michael van der Laan, MD; Michael J. Holroyde, PhD; Igor Singer, MD; Craig M. Pratt, MD, on Behalf of the SHock Inhibition Evaluation with azimiLiDe (SHIELD) Investigators

From the Division of Cardiology, St. Michael’s Hospital (P.D.), Toronto, Ontario, Canada; Klinikum Mannheim (M.B.), Universtatsklinikum, Mannheim, Germany; Health Care Research Center (H.R.A.-K., J.M.B., D.S.T., M.J.H.), Procter & Gamble Pharmaceuticals, Cincinnati, Ohio; J.W. Goethe University (S.H.H.), Department of Cardiology, Division of Electrophysiology, Frankfurt, Germany; Landkrankenhaus Coburg (J.B.), II Medizinische Klinik, Coburg, Germany; University of Miami School of Medicine (R.J.M.), Miami, Fla; Los Angeles Cardiology Associates (D.S.C.), Los Angeles, Calif; Procter & Gamble Pharmaceuticals (M.v.d.L.), Egham, United Kingdom; Methodist Medical Center (I.S.), Peoria, Ill; and The Methodist DeBakey Heart Center and the Section of Cardiology, Baylor College of Medicine (C.M.P.), Houston, Tex.

Correspondence to Dr Paul Dorian, St. Michael’s Hospital, 30 Bond St, Toronto, Ontario M5B 1W8, Canada. E-mail dorianp{at}smh.toronto.on.ca

Received October 1, 2004; revision received October 18, 2004; accepted October 19, 2004.

Background— Although implanted cardioverter defibrillators (ICDs) effectively treat sustained ventricular tachyarrhythmias, up to 50% of ICD recipients eventually require concomitant antiarrhythmic drug therapy to prevent symptomatic arrhythmia recurrences and hence reduce the number of device therapies.

Methods and Results— A total of 633 ICD recipients were enrolled in a randomized, double-blind, placebo-controlled study to evaluate the effect of daily doses of 75 or 125 mg of azimilide on recurrent symptomatic ventricular tachyarrhythmias and ICD therapies. Total all-cause shocks plus symptomatic ventricular tachycardia (VT) terminated by antitachycardia pacing (ATP) were significantly reduced by azimilide, with relative risk reductions of 57% (hazard ratio [HR]=0.43, 95% CI 0.26 to 0.69, P=0.0006) and 47% (HR=0.53, 95% CI 0.34 to 0.83, P=0.0053) at 75- and 125-mg doses, respectively. The reductions in all-cause shocks with both doses of azimilide did not achieve statistical significance. The incidence of all appropriate ICD therapies (shocks or ATP-terminated VT) was reduced significantly among patients taking 75 mg of azimilide (HR=0.52, 95% CI 0.30 to 0.89, P=0.017) and those taking 125 mg of azimilide (HR=0.38, 95% CI 0.22 to 0.65, P=0.0004). Five patients in the azimilide groups and 1 patient in the placebo group had torsade de pointes; all were successfully treated by the device. One patient taking 75 mg of azimilide had severe but reversible neutropenia.

Conclusions— Azimilide significantly reduced the recurrence of VT or ventricular fibrillation terminated by shocks or ATP in ICD patients, thereby reducing the burden of symptomatic ventricular tachyarrhythmia.

Key Words: drugs • cardioversion • defibrillation • antiarrhythmia agents • tachycardia

Related Article:

The Shocking Story of Azimilide

Ibrahim R. Hanna and Jonathan J. Langberg
Circulation 2004 110: 3624-3626. [Extract] [Full Text]

This article has been cited by other articles:

				P. Dorian, H. R. Al-Khalidi, S. H. Hohnloser, J. M. Brum, P. M. Dunnmon, C. M. Pratt, M. J. Holroyde, P. Kowey, and on behalf of the SHIELD (SHock Inhibition Evaluati Azimilide Reduces Emergency Department Visits and Hospitalizations in Patients With an Implantable Cardioverter-Defibrillator in a Placebo-Controlled Clinical Trial J. Am. Coll. Cardiol., September 23, 2008; 52(13): 1076 - 1083. [Abstract] [Full Text] [PDF]

				D. S. Cannom and B. Gidney Azimilide: Another Effort to Prevent Implantable Cardioverter-Defibrillator Shocks and Their Sequelae: Why it Is Important and How it Works J. Am. Coll. Cardiol., September 23, 2008; 52(13): 1084 - 1085. [Full Text] [PDF]

				J. Almendral and M. E. Josephson All Patients With Hemodynamically Tolerated Postinfarction Ventricular Tachycardia Do Not Require an Implantable Cardioverter-Defibrillator Circulation, September 4, 2007; 116(10): 1204 - 1212. [Full Text] [PDF]

				S. Singh and M. M. Murawski Implantable Cardioverter Defibrillator Therapy and the Need for Concomitant Antiarrhythmic Drugs Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2007; 12(3): 175 - 180. [Abstract] [PDF]

				B. N. Singh and E. Aliot Newer antiarrhythmic agents for maintaining sinus rhythm in atrial fibrillation: simplicity or complexity? Eur. Heart J. Suppl., September 1, 2007; 9(suppl_G): G17 - G25. [Abstract] [Full Text] [PDF]

				J. A. Ezekowitz, B. H. Rowe, D. M. Dryden, N. Hooton, B. Vandermeer, C. Spooner, and F. A. McAlister Systematic Review: Implantable Cardioverter Defibrillators for Adults with Left Ventricular Systolic Dysfunction Ann Intern Med, August 21, 2007; 147(4): 251 - 262. [Abstract] [Full Text] [PDF]

				A. K. Gehi, D. Mehta, and J. A. Gomes Evaluation and Management of Patients After Implantable Cardioverter-Defibrillator Shock JAMA, December 20, 2006; 296(23): 2839 - 2847. [Abstract] [Full Text] [PDF]

				Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) J. Am. Coll. Cardiol., September 5, 2006; 48(5): e247 - e346. [Full Text] [PDF]

				Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 746 - 837. [Full Text] [PDF]

				G. Klein, C. Lissel, A.-C. Fuchs, A. Gardiwal, H. Oswald, M. deSousa, A. M. Pichlmaier, R. Lichtinghagen, H. Geerlings, P. Lippolt, et al. Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study. Europace, August 1, 2006; 8(8): 618 - 624. [Abstract] [Full Text] [PDF]

				C. M. Pratt, H. R. Al-Khalidi, J. M. Brum, M. J. Holroyde, P. J. Schwartz, S. R. Marcello, M. Borggrefe, P. Dorian, A. J. Camm, and on behalf of the Azimilide Trials Investigators Cumulative Experience of Azimilide-Associated Torsades de Pointes Ventricular Tachycardia in the 19 Clinical Studies Comprising the Azimilide Database J. Am. Coll. Cardiol., August 1, 2006; 48(3): 471 - 477. [Abstract] [Full Text] [PDF]

				R. L. Page Antiarrhythmic Drugs for All Patients With an ICD? JAMA, January 11, 2006; 295(2): 211 - 213. [Full Text] [PDF]

				L.J. Jordaens and J.M. Mekel Electrical storm in the ICD era Europace, January 1, 2005; 7(2): 181 - 183. [Full Text] [PDF]

				I. R. Hanna and J. J. Langberg The Shocking Story of Azimilide Circulation, December 14, 2004; 110(24): 3624 - 3626. [Full Text] [PDF]