The implantable cardioverter defibrillator (ICD) reduces death in patients at risk for sustained ventricular arrhythmia, primarily by delivering high voltage shocks that terminate potentially fatal ventricular arrhythmias, according to background information in the article. ICD shocks are painful and patients may receive multiple ICD shocks. Such experiences are unpleasant and may lead to premature ICD battery depletion and continue to present a problem in the treatment of patients with ICD.
Antiarrhythmic drugs such as amiodarone and sotalol have the potential for reducing both appropriate and inappropriate shocks, but their relative efficacy to prevent shocks compared with standard therapy with a beta-blocker is unknown. Amiodarone has multiple effects on the heart; however, despite decades of use, it has never been compared with beta-blockers in a randomized controlled study. Sotalol is a beta-blocker with properties that are thought to help prevent ICD shocks, although previous studies have shown mixed results with this medication.
Stuart J. Connolly, M.D., of McMaster University, Hamilton, Ontario, Canada, and colleagues compared amiodarone plus a beta-blocker, sotalol alone, or standard beta-blocker therapy alone for prevention of ICD shocks in the OPTIC study. The randomized controlled trial included 412 patients from 39 out-patient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, and was conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia (VT - a rapid, abnormal heart rhythm) or ventricular fibrillation (VF). Patients were randomized to treatment for 1 year of amiodarone plus beta-blocker, sotalol alone, or beta-blocker alone.
A significant reduction (56 percent) was observed in the risk of a shock when the 274 patients randomized to either of the 2 active treatment groups, sotalol or amiodarone plus beta-blocker, were compared with the 138 patients randomized to beta-blocker alone. Amiodarone plus beta-blocker significantly reduced (73 percent) the risk of shock compared with beta-blocker alone and sotalol (57 percent reduction). There was a non-significant trend for sotalol to reduce the risk of shock compared with beta-blocker alone.
In patients randomized to beta-blocker alone, the annual risk of any shock was 38.5 percent. The annual risk of an appropriate shock (for VT or VF) was 22.0 percent and the annual risk of an inappropriate shock (mostly for supraventricular arrhythmia) was 15.4 percent. Both types of shock were significantly reduced by amiodarone plus beta-blocker but not significantly reduced by sotalol. Adverse pulmonary and thyroid events, and symptomatic bradycardia (abnormally slow heartbeat) were more common among patients receiving amiodarone.
"Should amiodarone or sotalol be administered immediately after ICD implantation or some time before a first shock occurs? By delaying therapy, one reduces the risk of drug-related adverse effects; however, this needs to be balanced against the adverse experience of receiving shock therapy. Fourteen patients (10 percent) receiving beta-blocker alone experienced their first shock as multiple (2 shocks or more within 24 hours). On the other hand, a majority of patients did not have a shock in the year of follow-up in this OPTIC trial. Therapeutic decisions should be individualized, taking into account possible improvements in quality of life and small but increased risks of drug-related adverse effects," the authors conclude.
(JAMA. 2006;295:165-171. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This study was funded by St. Jude Medical, Sylmar, Calif. Co-authors Connolly, Dorian, and Hohnloser have received research grants from St. Jude Medical. As a St. Jude Medical employee, co-author Dr. Fain is a stockholder in the company. None of the other authors reported disclosures.
Editorial: Antiarrhythmic Drugs for All Patients With an ICD?
In an accompanying editorial, Richard L. Page, M.D., of the University of Washington School of Medicine, Seattle, comments on the study by Connolly and colleagues.
"Based on the study by Connolly et al and taken in context with previous studies, should cardiologists advocate empirical antiarrhythmic therapy for patients receiving an ICD? Importantly, the OPTIC study applies primarily to ICDs placed as secondary prevention, in which sustained ventricular arrhythmias have been observed clinically. There are less data to support the use of antiarrhythmic agents in patients with prophylactic or primary prevention ICD therapy and this group appears to have less frequent need for such therapy; thus, empirical antiarrhythmic therapy cannot be recommended for this setting. For patients who receive an ICD for secondary prevention, one could argue for empirical initiation of amiodarone or sotalol. As per the OPTIC study, such therapy would reduce the absolute risk of shock by 28 percent or 14 percent, respectively, and as such would provide a substantial benefit in comfort and possibly quality of life." (JAMA. 2006;295:211-213. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Dr. Page has previously served as consultant to Astra Zeneca, GlaxoSmithKline, Cardiome, Reliant Pharmaceuticals, Forrest Research, and Procter & Gamble Pharmaceuticals. He is now a consultant to Berlex Laboratories, Alza (a subsidiary of Johnson & Johnson), and Sanofi Synthelabo.