Since many of the patients who have AF have significant structural heart disease, attempts should be made to use drugs with mortality-neutral effects. Currently, amiodarone has the largest clinical experience in patients with structural heart disease. The South American GESICA trial (78) demonstrated a reduced morbidity and mortality in patients treated with amiodarone who had severe CHF. Although CAMIAT (79) and EMIAT trials (80) demonstrated a reduced risk of sudden death in patients treated with amiodarone, there was no significant difference in overall mortality compared to patients treated with placebo. The CASCADE trial (81) demonstrated an improved survival in patients who survived sudden death when treated with amiodarone vs electrophysiologic-guided standard antiarrhythmic therapy. In a meta-analysis (82) of over 6500 patients in 20 trials utilizing amiodarone, post-MI or in CHF, there was a 13% decrease in total mortality in treated patients. Although these trials were not designed to test the safety of amiodarone in the control of AF, they nevertheless demonstrated that amiodarone does not increase mortality in patients with severe structural heart disease or CHF who are at high risk of sudden death. A recent Canadian trial showed amiodarone to be more effective than either sotalol or propafenone in the long-term suppression of AF (82A).
Amiodarone, from a mortality standpoint, appears to be the drug of choice in patients with heart failure or cardiomyopathy. Unfortunately, it has the most significant organ-toxicity profile of any drug. The incidence of severe hepatotoxicity is <3%, neurotoxicity is approx 20%, pulmonary toxicity is 0.5-10%, and thyroid toxicity is 2-24% (83). Therefore, careful initial screening of liver, thyroid, and pulmonary tests as well as long-term serial follow-up of the various organ toxic effects are mandatory. The toxic effects are dose-related and cumulative. The decision to use amiodarone should take into account the age of the patients and the expected number of years that it will be used. The term "low-dose" amiodarone has been coined for the use of doses less than or equal to 200 mg per d to treat AF (less than the typical dose for treating VT). For patients being treated de novo for AF, maintenance doses of this quantity are often adequate. In patients who have failed other antiarrhythmics agents, higher doses are often required to maintain normal sinus rhythm, thus increasing the risk of organ toxicity.
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