Is amiodarone effective for the prevention of sudden cardiac death in patients at increased risk?
Although not a substitute for an implantable cardioverter-defibrillator (ICD), amiodarone is effective for the primary prevention of sudden cardiac death when compared with placebo (number needed to treat [NNT] = 47; 95% confidence interval [CI], 33 to 100), but it does not significantly lower all-cause mortality in those at high risk. Amiodarone increases the risk of all-cause mortality when used for secondary prevention (number needed to harm [NNH] = 15; 95% CI, 5 to 91) and should not be used in this setting. Adverse effects of therapy include thyroid and pulmonary toxicity.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)
Sudden cardiac death causes approximately 25% of worldwide cardiac-related deaths each year.2 ICDs are standard therapy for the prevention of sudden cardiac death in patients who have an expected survival of more than one to two years and have risk factors such as a history of cardiac arrest, sustained ventricular tachycardia with hemodynamic compromise, a familial cardiac condition with a high risk of sudden cardiac death, or heart failure with significant left ventricular dysfunction.2–5 Despite this, high up-front costs limit the use of ICDs in resource-constrained areas, and some patients may not wish to have an ICD placed. The authors of this review sought to determine whether amiodarone, a class III antiarrhythmic, would be helpful for the prevention of sudden cardiac death in these settings.1
This Cochrane review included 24 randomized trials and 9,997 patients.1 For primary prevention—that is, for patients at high risk of arrhythmia but no history of cardiac arrest or ventricular arrhythmia–associated syncope—amiodarone in a dosage of 200 to 400 mg daily (after a loading dose) decreased the risk of sudden cardiac death when compared with placebo (NNT over six months to five years = 47; 95% CI, 33 to 100). Amiodarone also decreased the risk of cardiac mortality (NNT over six months to five years = 46; 95% CI, 27 to 154), but not all-cause mortality when compared with placebo. Amiodarone did not decrease sudden cardiac death when compared with other antiarrhythmics, but it did reduce all-cause mortality vs. other pharmacologic agents (NNT over six months to five years =15; 95% CI, 12 to 42). Amiodarone was not directly compared with ICDs for primary prevention.
For secondary prevention—that is, in patients with a history of cardiac arrest or ventricular arrhythmia–associated syncope—amiodarone had no effect on sudden cardiac death when compared with placebo, but it did increase all-cause mortality (NNH over six months to five years = 15; 95% CI, 5 to 91). When compared with other antiarrhythmics, amiodarone had no significant effect on sudden cardiac death or all-cause mortality. Patients taking amiodarone for prevention were more likely to develop hyperthyroidism (NNH over six months to five years = 31; 95% CI, 8 to 344), hypothyroidism (NNH over six months to five years = 38; 95% CI, 29 to 274), or pulmonary effects (NNH over six months to five years = 91; 95% CI, 46 to 432).
Major guidelines from the United States and Europe recommend ICDs for patients at high risk of arrhythmia and with a life expectancy greater than one to two years.2–5 Although amiodarone is mentioned as one of the few antiarrhythmics not to increase mortality in heart failure, it is not considered a substitute for ICD therapy, which is covered by insurance in the United States. In resource-constrained areas where ICDs are not available, or for patients who do not wish to receive an ICD, amiodarone may be helpful in the primary prevention of sudden cardiac death, but it has no role in secondary prevention, including in patients who have an ICD.
The practice recommendations in this activity are available at http://summaries.cochrane.org/CD008093.
editor's note: The numbers needed to treat and numbers needed to harm reported in this Cochrane for Clinicians were calculated by AFP medical editors based on raw data provided in the original Cochrane review.
The views expressed in this article are those of the author and do not reflect the official policy or position of the U.S. government, the Department of the Army, or the Department of Defense.