Objective: To discuss the role of amiodarone for the maintenance of normal sinus rhythm in patients with atrial fibrillation (AF) and review the clinical trial data evaluating the efficacy and safety of amiodarone in patients with AF. Data Sources: A MEDLINE search was used to identify pertinent literature. Additional references were identified from the articles obtained in the search. Key search terms were atrial fibrillation, amiodarone, and sinus rhythm. Study Selection: All studies available at the time the article was prepared evaluating the efficacy and safety of amiodarone in AF were included. In addition, review articles discussing the role of amiodarone in AF were selected. Data Extraction: NO large, prospective, randomized trials have been performed. Data from 8 nonrandomized and 2 randomized trials are reported. Information derived from review articles is discussed. Data Synthesis: In patients with AF, maintenance of normal sinus rhythm is desirable to eliminate symptoms, improve functional capacity, and reduce the risk of thromboembolic complications. Class IA agents traditionally have been used; however, concerns about long-term effects on mortality have focused attention on other agents such as amiodarone. A number of nonrandomized, uncontrolled trials have found amiodarone to be effective for maintaining normal sinus rhythm in patients with AF that is refractory to conventional agents. Two randomized, nonblind trials have found amiodarone's efficacy to be equal to or superior to that of class IA drugs. The findings of these trials must be weighed, however, against the significant potential for toxicity and drug interactions associated with amiodarone. Cardiovascular toxicities, including proarrhythmic effects, appear to be relatively rare. In contrast, noncardiovascular effects are common and potentially serious. Conclusions: Although the preliminary data using amiodarone in AF are encouraging, many questions remain unanswered. Prospective, randomized trials are needed to evaluate the long-term efficacy and safety of amiodarone in patients with AF. Studies also are needed to determine the optimal dosing regimen. Until these data are available, each patient must be evaluated individually, taking into account the relative benefits and risks of therapy. Amiodarone may be particularly useful in patients with significant risks for proarrhythmia and those whose AF is refractory to traditional therapy.
In Silico Assessment of Efficacy and Safety of IKur Inhibitors in Chronic Atrial Fibrillation: Role of Kinetics and State-Dependence of Drug Binding