Antiarrhythmics Versus Implantable Defibrillators (AVID)
Antiarrhythmics Versus Implantable Defibrillators (AVID)
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.
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.
Men & women with VF, VT with syncope, or VT without syncope, but with ejection fraction
 less than or equal to .40 & systolic blood pressure less than 80 mm Hg, chest pain , or
 near syncope.