New and emerging antiarrhythmic drugs for atrial fibrillation: what may become available to the clinician in the near future.
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major cause of morbidity. In the past decade, there have been significant advances in the nonpharmacologic management of AF. However, despite these advances there continues to be a great need for antiarrhythmic drugs to suppress AF. Existing medications have moderate efficacy for AF termination and suppression and have significant associated side effects, limiting their use. The need for new therapies has spawned the growth of several exciting drugs at various stages of development for the medical management of AF. Some agents are derivatives of currently available compounds, whereas others have been newly developed to focus on novel ion current targets. Dronedarone is the first antiarrhythmic agent in a decade to be recommended for approval by the US Food and Drug Administration for the management of AF. It is expected to a have a dramatically improved side effect profile, which likely will be the key factor in its prominence in our armamentarium in the future; however, dronedarone appears to have only moderate efficacy. Other novel agents are in various stages of development. Vernakalant, an "atrial selective" compound, will be useful in the acute chemical cardioversion of AF but not atrial flutter. Although vernakalant is similar in efficacy to ibutilide, it carries a significantly reduced risk of torsades de pointes. Ranolazine, initially developed for treating chronic angina, has important effects on ion currents potentially useful in arrhythmia management. Clinical trials specifically studying AF suppression will need to be performed before the utility of ranolazine can be extended. It is hoped that as our understanding of the pathophysiology of AF improves, innovative targets for pharmacologic therapy will emerge. However, the challenge of proving efficacy and safety in large randomized controlled trials will remain for any promising new agent.
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Peter J. Zimetbaum, MD Division of Cardiology, Beth Israel Deaconess Medical Center, 185 Pilgrim Road, Baker 4, Boston, MA 02115, USA. pzimetba@bidmc.harvard.edu.
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Peter J
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