Circulation. 2004;109:990-996
Published online before print February 16, 2004, doi: 10.1161/01.CIR.0000117090.01718.2A
Published online before print February 16, 2004, doi: 10.1161/01.CIR.0000117090.01718.2A
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(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
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
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