This Article Full Text Full Text (PDF) All Versions of this Article: 109/8/990    most recent 01.CIR.0000117090.01718.2Av1 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 Camm, A. J. Search for Related Content PubMed PubMed Citation Articles by Camm, A. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Attack Related Collections Arrhythmias, clinical electrophysiology, drugs

(Circulation. 2004;109:990-996.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Mortality in Patients After a Recent Myocardial Infarction

A Randomized, Placebo-Controlled Trial of Azimilide Using Heart Rate Variability for Risk Stratification

A. John Camm, MD; Craig M. Pratt, MD; Peter J. Schwartz, MD; Hussein R. Al-Khalidi, PhD; Maria J. Spyt, MD; Michael J. Holroyde, PhD; Roger Karam, MD; Edmund H. Sonnenblick, MD; Jose M.G. Brum, MD, on Behalf of the AzimiLide post Infarct surVival Evaluation (ALIVE) Investigators

From the Department of Cardiology, St George’s Hospital, London, UK (A.J.C.); Baylor College of Medicine, Houston, Tex (C.M.P.); Department of Cardiology, Policlinico S Matteo, IRRCS, and University of Pavia, Italy (P.J.S.); Procter & Gamble Pharmaceuticals Inc, Cincinnati, Ohio (H.R.A., M.J.S., M.J.H., R.K., J.M.G.B.); and Albert Einstein College of Medicine, New York, NY (E.H.S.).

Correspondence to Prof A. John Camm, MD, Department of Cardiology, St George’s Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK. E-mail jcamm{at}sghms.ac.uk

Received June 2, 2003; de novo received September 24, 2003; accepted November 14, 2003.

Background— Depressed left ventricular function (LVF) and low heart rate variability (HRV) identify patients at risk of increased mortality after myocardial infarction (MI). Azimilide, a novel class III antiarrhythmic drug, was investigated for its effects on mortality in patients with depressed LVF after recent MI and in a subpopulation of patients with low HRV.

Methods and Results— A total of 3717 post-MI patients with depressed LVF were enrolled in this randomized, placebo-controlled, double-blind study of azimilide 100 mg on all-cause mortality. Placebo patients with low HRV had a significantly higher 1-year mortality than those with high HRV (>20 U; 15% versus 9.5%, P<0.0005) despite nearly identical ejection fractions. No significant differences were observed between the 100-mg azimilide and placebo groups for all-cause mortality in either the "at-risk" patients identified by depressed LVF (12% versus 12%) or the subpopulation of "high-risk" patients identified by low HRV (14% versus 15%) or for total cardiac or arrhythmic mortality. Significantly fewer patients receiving azimilide developed atrial fibrillation than did patients receiving placebo (0.5% versus 1.2%, P<0.04). The incidences of torsade de pointes and severe neutropenia (absolute neutrophil count 500 cells/µL) were slightly higher in the azimilide group than in the placebo group (0.3% versus 0.1% for torsade de pointes and 0.9% versus 0.2% for severe neutropenia).

Conclusions— Azimilide did not improve or worsen the mortality of patients after MI. Low HRV independently identified a subpopulation at high risk of mortality.

Key Words: azimilide • antiarrhythmia agents • trials • heart rate

This article has been cited by other articles:

				S. Zaman, G. Sivagangabalan, A. Narayan, A. Thiagalingam, D. L. Ross, and P. Kovoor Outcomes of Early Risk Stratification and Targeted Implantable Cardioverter-Defibrillator Implantation After ST-Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention Circulation, July 21, 2009; 120(3): 194 - 200. [Abstract] [Full Text] [PDF]

				H. V. Huikuri, M.J. P. Raatikainen, R. Moerch-Joergensen, J. Hartikainen, V. Virtanen, J. Boland, O. Anttonen, N. Hoest, L. V.A. Boersma, E. S. Platou, et al. Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction Eur. Heart J., March 2, 2009; 30(6): 689 - 698. [Abstract] [Full Text] [PDF]

				L. Eckardt, G&#x.;n. Breithardt, and S. Hohnloser CHAPTER 30 Ventricular Tachycardia and Sudden Cardiac Death ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				Authors/Task Force Members, K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) Eur. Heart J., October 1, 2008; 29(19): 2388 - 2442. [Full Text] [PDF]

				K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, A. W. Hoes, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) Eur J Heart Fail, October 1, 2008; 10(10): 933 - 989. [Full Text] [PDF]

				J. J. Goldberger, M. E. Cain, S. H. Hohnloser, A. H. Kadish, B. P. Knight, M. S. Lauer, B. J. Maron, R. L. Page, R. S. Passman, D. Siscovick, et al. American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death: A Scientific Statement From the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention J. Am. Coll. Cardiol., September 30, 2008; 52(14): 1179 - 1199. [Full Text] [PDF]

				J. J. Goldberger, M. E. Cain, S. H. Hohnloser, A. H. Kadish, B. P. Knight, M. S. Lauer, B. J. Maron, R. L. Page, R. S. Passman, D. Siscovick, et al. American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death: A Scientific Statement From the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention Circulation, September 30, 2008; 118(14): 1497 - 1518. [Full Text] [PDF]

				I. Savelieva and J. Camm Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches Europace, June 1, 2008; 10(6): 647 - 665. [Abstract] [Full Text] [PDF]

				A. H. Glassman, J. T. Bigger, M. Gaffney, and L. T. Van Zyl Heart Rate Variability in Acute Coronary Syndrome Patients With Major Depression: Influence of Sertraline and Mood Improvement Arch Gen Psychiatry, September 1, 2007; 64(9): 1025 - 1031. [Abstract] [Full Text] [PDF]

				K. Fox, J. S. Borer, A. J. Camm, N. Danchin, R. Ferrari, J. L. Lopez Sendon, P. G. Steg, J.-C. Tardif, L. Tavazzi, M. Tendera, et al. Resting Heart Rate in Cardiovascular Disease J. Am. Coll. Cardiol., August 28, 2007; 50(9): 823 - 830. [Abstract] [Full Text] [PDF]

				O. A. Centurion The Open Artery Hypothesis: Beneficial Effects and Long-term Prognostic Importance of Patency of the Infarct-Related Coronary Artery Angiology, February 1, 2007; 58(1): 34 - 44. [Abstract] [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]

				F. Lombardi, M. Borggrefe, W. Ruzyllo, B. Luderitz, and for the A-COMET-II Investigators Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial Eur. Heart J., September 2, 2006; 27(18): 2224 - 2231. [Abstract] [Full Text] [PDF]

				Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [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]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [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]

				C. Falcone, M. P. Buzzi, C. Klersy, and P. J. Schwartz Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease Circulation, September 27, 2005; 112(13): 1959 - 1964. [Abstract] [Full Text] [PDF]

				P. Dorian, M. Borggrefe, H. R. Al-Khalidi, S. H. Hohnloser, J. M. Brum, D. S. Tatla, J. Brachmann, R. J. Myerburg, D. S. Cannom, M. van der Laan, et al. Placebo-Controlled, Randomized Clinical Trial of Azimilide for Prevention of Ventricular Tachyarrhythmias in Patients With an Implantable Cardioverter Defibrillator Circulation, December 14, 2004; 110(24): 3646 - 3654. [Abstract] [Full Text] [PDF]

				S. H. Hohnloser, K. H. Kuck, P. Dorian, R. S. Roberts, J. R. Hampton, R. Hatala, E. Fain, M. Gent, S. J. Connolly, and the DINAMIT Investigators Prophylactic Use of an Implantable Cardioverter-Defibrillator after Acute Myocardial Infarction N. Engl. J. Med., December 9, 2004; 351(24): 2481 - 2488. [Abstract] [Full Text] [PDF]

				I. Savelieva and A. John Camm Atrial fibrillation and heart failure: natural history and pharmacological treatment Europace, January 1, 2003; 5(s1): S5 - S19. [Abstract] [Full Text] [PDF]