Preventing sudden cardiac death: Should amiodarone be abandoned in the ICD era?

Sudden cardiac death is a leading cause of mortality in industrialized countries. Several large trials have provided convincing evidence of the effectiveness of implantable cardioverter defibrillators (ICDs) in primary and secondary prevention. Because of this and the growing awareness of the sometimes serious side effects of antiarrhythmic drugs, pharmacologic treatment of malignant arrhythmias has been largely abandoned. One of the few exceptions is amiodarone (Cordarone, Pacerone). Although this agent also carries the risk of significant adverse effects, early studies suggested that it has the potential to suppress ventricular arrhythmias and might prolong the life of ventricular arrhythmia patients who are at risk for sudden death.1 However, subsequent studies of patients who survived myocardial infarction and patients with congestive heart failure or ventricular tachycardia showed almost uniformly that only arrhythmic, but not overall, mortality was reduced by amiodarone treatment.2 More recently, several large trials compared the efficacy of amiodarone and the ICD on mortality in high-risk populations.

In this issue of Cardiology Review, Bokhari and colleagues (page 21) review long-term follow-up data from one such trial, the Canadian Implantable Defibrillator Study. In 120 patients who were followed up for more than 5 years, the total annual mortality rate in the amiodarone group was twice that in the ICD group (amiodarone: ICD hazard ratio, 2.01 [1.09—

3.72]). Moreover, 50% of patients taking amiodarone had side effects that required discontinuation of the drug or dose reduction. The authors concluded that in this subset of patients, the mortality advantage of the ICD increased over time.

These results were confirmed by the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) in patients with ischemic or nonischemic cardiomyopathy (New York Heart Association class II and III; median ejection fraction of 25%).3 The study population was assigned to either conventional treatment plus

placebo, conventional treatment plus amiodarone, or prophylactic ICD implantation. Amiodarone conferred no mortality benefit over placebo, but the 5-year absolute mortality rate in the ICD cohort was reduced by 7.2% compared with the overall population.

In summary, these results indicate that in the era of ICDs, amiodarone prophylaxis alone is not justified for the prevention of sudden cardiac death if an ICD is an option. Given the drug’s antiarrhythmic efficacy, it may have an adjunctive role in ICD recipients who have frequent ventricular arrhythmias triggering ICD discharges.