Medical management of atrial fibrillation: future directions.
Atrial fibrillation is the most common arrhythmia that requires treatment, and although ablation is appropriate in many cases, anti-arrhythmic drug therapy remains the first and most appropriate therapy in most patients. Currently available antiarrhythmic drugs are limited by modest efficacy and significant toxicity. Cardiac toxicity relates to effects on the ventricle, especially in prolonging the QT interval and causing torsades de pointes. Amiodarone, an agent with multiple antiarrhythmic effects, is unique in its relative lack of pro-arrhythmia, although its non-cardiac toxicities limit its use. Some investigational agents are directed at multiple ion channels, or are designed to be analogs of amiodarone. The other line of investigation focuses on the antiarrhythmic action of agents that affect novel ion channel targets. Basic and early clinical studies show promise for drugs that provide atrial antiarrhythmic effects without ventricular pro-arrhythmia by affecting the atrium preferentially or selectively (inhibiting the I(TO) and I(Kur) currents, respectively). Future drugs may possess preferential effects on the remodeled atrium (and as such would be selective for patients with atrial fibrillation). It is hoped that efforts to develop new drugs, including those with preferential effects on the atrium, will provide therapy with greater efficacy and safety.
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Richard L
RL
Department of Internal Medicine (Cardiology Division), University of Washington School of Medicine, Seattle, Washington 98195-6422, USA. rpage@u.washington.edu
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004358:Drug Therapy / Q000639:trends; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008465:Mechanoreceptors / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D016171:Torsades de Pointes / Q000139:chemically induced
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015507:Drugs, Investigational; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers