Antiarrhythmics Versus Implantable Defibrillators Study Research Articles

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit

OBJECTIVESThe goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD).BACKGROUNDTreatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD.METHODSData for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated.RESULTSFactors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 ± 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 ± 0.07 (se) years (two-sided p = 0.05).CONCLUSIONSPatients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.

Amiodarone: clinical trials.

Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This article reviews the results and clinical implications of primary and secondary prevention trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction primary prevention trials include the European Myocardial Infarct Amiodarone Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In congestive heart failure patients, amiodarone was studied as a primary prevention strategy in two pivotal trials: Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiac en Argentina (GESICA) and Amiodarone in Patients With Congestive Heart Failure and Asymptomatic Ventricular Arrhythmia (CHF-STAT). Amiodarone was associated with a neutral overall survival and a trend toward improved survival in nonischemic cardiomyopathy patients in CHF/STAT and improved survival in GESICA. In post-myocardial infarction patients with nonsustained ventricular tachycardia and a depressed ejection fraction, the Multicenter Automatic Defibrillator Implantation Trial (MADIT) demonstrated that implantable cardioverter-defibrillators (ICD) statistically improved survival compared to the antiarrhythmic drug arm, most of whose patients were taking amiodarone. In patients with histories of sustained ventricular tachycardia or ventricular fibrillation, the Cardiac Arrest Study in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared to other drugs guided by serial Holter or electrophysiologic studies. However, arrhythmic death rates were high in both treatment arms of the study. Several secondary prevention trials, including the Antiarrhythmics Versus Implantable Defibrillators Study (AVID), the Canadian Implantable Defibrillator Study (CIDS), and the Cardiac Arrest Study Hamburg (CASH), have demonstrated the superiority of ICD therapy compared to empiric amiodarone in improving overall survival. Based on the above findings, amiodarone is safe to use in post-myocardial infarction and congestive heart failure patients that need antiarrhythmic therapy. Although amiodarone is effective in treating malignant arrhythmias, high-risk patients should be considered for an ICD as frontline therapy.

Navigation in the mega-trials waters: reflections on the multicenter automatic defibrillator implantation trial and the antiarrhythmics versus implantable defibrillators study

Today, cardiology seems to be driven by mega-trials and meta-analyses. Guidelines published by scientific and professional cardiovascular societies, such as the American Heart Association, the American College of Cardiology, and the European Society of Cardiology, follow the rules of evidence-based medicine. Such evidence is not always sufficiently conclusive to practice clinically helpful medicine. Sometimes, relatively small trials, such as the Multicenter Automatic Defibrillator Implantation Trial and the Antiarrhythmics Versus Implantable Defibrillators study, may be taken as guides for current clinical decisions and as inspiration for future investigations. Large mega-trials with a great lack of homogeneity among the recruited patients are less important for clinically helpful medicine than studies enrolling well-defined, high-risk patients. It is probably important to acknowledge that the best possible treatment for many patients with ventricular tachyarrhythmias remains obscure. Among these situations are the following: (1) sustained ventricular tachycardia (VT) in patients without coronary artery disease; (2) sustained, nonsyncopal VT in patients with coronary artery disease and left ventricular dysfunction; (3) post myocardial infarction survivors with an ejection fraction ≤35%, frequent/complex ventricular arrhythmias, depressed heart rate variability, and inducible sustained ventricular tachyarrhythmias during electrophysiologic study. Many studies are being conducted to add light where uncertainty exists, but probably only a few will contribute to the practice of clinically helpful medicine, although some will be used to produce meta-analysis to sustain evidence-based medicine.