Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification

Circulation. 2004 Mar 2;109(8):990-6. doi: 10.1161/01.CIR.0000117090.01718.2A. Epub 2004 Feb 16.


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 < or =500 cells/microL) 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / mortality
  • Arrhythmias, Cardiac / prevention & control
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / prevention & control
  • Double-Blind Method
  • Female
  • Heart Rate*
  • Humans
  • Hydantoins
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Imidazolidines*
  • Life Tables
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology
  • Neutropenia / chemically induced
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Potassium Channel Blockers / adverse effects
  • Potassium Channel Blockers / therapeutic use*
  • Risk Factors
  • Survival Analysis
  • Torsades de Pointes / etiology
  • Torsades de Pointes / prevention & control
  • Treatment Outcome
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / etiology


  • Anti-Arrhythmia Agents
  • Hydantoins
  • Imidazoles
  • Imidazolidines
  • Piperazines
  • Potassium Channel Blockers
  • azimilide