New horizons in antiarrhythmic therapy: will novel agents overcome current deficits?
Pharmacologic antiarrhythmic therapy is the most commonly used treatment in most patients with atrial fibrillation (AF), but currently available agents are limited by risks that may offset the benefits of sinus rhythm. The development of antiarrhythmic agents with the potential for fewer adverse ventricular effects and less extracardiac toxicity is a primary aim of current investigations. At present, pharmacologic research is actively focused on developing antiarrhythmic agents with multiple or novel ion channel effects. There are 4 agents that act by simultaneously blocking multiple ion channels that are currently under regulatory review: azimilide dihydrochloride, tedisamil, dronedarone, and vernakalant (RSD-1235). In addition, agents with mechanisms of action that differ from those of existing agents (eg, gap junction modulators) are under review, as is the use of nonantiarrhythmic agents (eg, renin-angiotensin system antagonists, statins, n-3 polyunsaturated fatty acids) to alter the cardiac substrate and suppress AF in some patient subtypes.
Conway
Emily
E
Division of Cardiovascular Diseases, Main Line Health Heart Center, Wynnewood, Pennsylvania 19096, USA.
Musco
Simone
S
Kowey
Peter R
PR
D000638:Amiodarone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000840:Anisoles / Q000494:pharmacology / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003521:Cyclopropanes / Q000494:pharmacology / Q000627:therapeutic use; D000077764:Dronedarone; D006801:Humans; D006827:Hydantoins; D048289:Imidazolidines / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; D006827:Hydantoins; D048289:Imidazolidines; D010879:Piperazines; D011759:Pyrrolidines; C086123:azimilide; C524581:vernakalant; C059921:tedisamil; D000077764:Dronedarone; D000638:Amiodarone