Antiarrhythmics Versus Implantable Defibrillators (AVID)
Condition: Arrhythmia; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Tachycardia, Ventricular; Ventricular Fibrillation
MeSH terms: Cardiovascular Diseases; Heart Diseases; Tachycardia; Ventricular Fibrillation; Tachycardia, Ventricular; Death, Sudden, Cardiac; Death, Sudden
Study type: Interventional
Phase: Phase 3

Summary: 
      To evaluate if use of an implantable cardiac defibrillator (ICD) results in reduction in
      total mortality, when compared with conventional pharmacological therapy, in patients
      resuscitated from sudden cardiac death who are otherwise at very high risk of mortality from
      arrhythmic causes.
    

Detailed description: 
      BACKGROUND:

      Sudden cardiac death is believed to account for a substantial proportion of deaths in
      patients with evidence of cardiovascular disease. The exact proportion of cardiac deaths that
      are classified as being sudden varies depending on the population, the underlying disease,
      and the definition of sudden death. Various estimates suggest that about 500,000 sudden
      cardiac deaths occur annually in the United States alone. The majority of sudden cardiac
      deaths are thought to be due to ventricular fibrillation (VF) or tachycardia (VT).

      The commonest approach to preventing sudden cardiac death has been by the use of drugs that
      suppress ventricular ectopy. The rational for this approach is based upon an association
      between the presence or frequency of ventricular arrhythmia and subsequent mortality in
      several studies. None of the randomized controlled studies of numerous 'classical'
      antiarrhythmic agents (other than beta-blockers, which have only a modest effect on
      arrhythmia suppression) have demonstrated a reduction in sudden or non-sudden cardiac
      mortality. Indeed, in the recent Cardiac Arrhythmia Suppression Trial (CAST), two class Ic
      anti-arrhythmic agents demonstrated a 2.5 fold increase in the risk of sudden and non-sudden
      cardiac deaths despite excellent suppression of ventricular arrhythmia.

      Given the disappointing results of most pharmacologic approaches to preventing sudden death,
      many investigators have turned to non-pharmacologic approaches such as surgery (endocardial
      resection, stellate ganglionectomy) or the implantation of devices that recognize VT or VF
      and deliver a shock. The greatest interest has been generated by work on the implantable
      cardiac defibrillator.

      The study was reviewed by an ad hoc working group, the Clinical Applications and Prevention
      Advisory Committee, and several members of the Cardiology Advisory Committee prior to review
      and approval by the National Heart, Lung, and Blood Advisory Council in September 1991. The
      Request for Proposals was released in February 1992.

      DESIGN NARRATIVE:

      At approximately 28 clinical sites, patients with ventricular tachycardia or ventricular
      fibrillation were screened. Those with ventricular fibrillation or serious ventricular
      tachycardia were entered into a registry for long-term mortality follow-up using the National
      Death Index. Patients with the prospect of long-term benefit from an ICD and/or
      antiarrhythmic drug therapy and without exclusions to an ICD or to amiodarone and without a
      transient or correctible cause of the index event were entered into the trial.

      Patients meeting the criteria were randomized to treatment with an ICD or treatment with
      antiarrhythmic drug therapy. Allocation was stratified by clinical site and index arrhythmia,
      either ventricular fibrillation or ventricular tachycardia. Patients assigned to the
      antiarrhythmic drug therapy and without contraindications to sotalol underwent
      subrandomization to either empiric amiodarone or sotalol, the latter treatment guided by
      either ambulatory monitoring or electrophysiologic testing. Patients who, after
      subrandomization, had low levels (less than 30 beats per hour) of ventricular ectopic beats
      and no inducible ventricular arrhythmias at electrophysiologic study were not treated with
      sotalol and instead received empiric amiodarone. The AVID protocol allowed usual clinical
      practice but restricted interventions to state-of-the art ICD devices and first-line
      antiarrhythmic agents to amiodarone and sotalol. Patients who could not take amiodarone were
      not included in the trial. The protocol encouraged the use of concurrent drugs such as
      angiotensin-converting enzyme inhibitors, aspirin, and beta-blockers when appropriate,
      administered before randomization and maintained throughout the study. The primary endpoint
      was total mortality. Secondary endpoints were cost of health care and quality of life.
      Nonlethal events such as ICD shock, sustained arrhythmia, or syncope were tabulated.

      Patients were followed every three months for assessment of secondary endpoints, to record
      therapies delivered by the ICD and potential adverse effects of the ICD, and to assess
      compliance and potential adverse symptoms in patients treated with antiarrhythmic drugs. A
      12-lead electrocardiogram was obtained every six months, and appropriate laboratory and
      pulmonary tests were performed at six and eighteen months on patients receiving amiodarone.
      The average follow-up was expected to be 2.6 years. Analysis was done by intention-to-treat.
      The outcome of primary interest in the subrandomization between sotalol and amiodarone was
      the time to withdrawal from assigned therapy.

      After a review of the data by the Data and Safety Monitoring Board, the AVID study was
      stopped early on April 7, 1997 because of the findings that after one year, patients in the
      defibrillator group experienced a nearly 38 percent reduction in deaths compared to the group
      of patients taking an antiarrhythmic drug. The defibrillator group had about a 25 percent
      reduction in deaths in years two and three.
    

Intervention name(s): defibrillators, implantable; amiodarone amiodarone; sotalol
Intervention type(s): Device; Drug; Drug
Intervention MeSH terms: Amiodarone; Sotalol
Allocation: Randomized
Primary purpose: Treatment