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New Rhythm control drugs slated for Atrial Fib. (Azimilide May Get Marketing Approval Soon).

BERLIN -- A surprisingly large crop of new antiarrhythmic agents is in development for atrial fibrillation.

This flurry of research activity contrasts with the drubbing that the rhythm control strategy sustained after the release of results from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial. The National Heart, Lung, and Blood Institute-sponsored study randomized more than 4,000 elderly patients with atrial fibrillation (AF) to rate control or rhythm control. AFFIRM showed a trend toward improved outcomes with rate control, which elevated this safer and simpler therapeutic approach to first-line therapy status in the minds of many experts.

Nevertheless, there remains a school of thought that holds the real lesson of AFFIRM is the need for better antiarrhythmic agents.

New antiarrhythmic agents for AF are a priority, Dr. Jean-Yves Le Heuzey said at the 24th Congress of the European Society of Cardiology. That's because the incidence of this most common of the sustained arrhythmias is rapidly increasing with the graying of the population. With improved survival following acute MI, there is a growing role for hybrid therapies combining drugs and nonpharmacologic interventions, such as radiofrequency ablation or surgery. Further, the safety of current drugs isn't optimal.

New directions in antiarrhythmic therapy being explored for AF include novel formulations of class I antiarrhythmic agents, coupling agents that act upon connexins, specific bradycardic agents, and serotonin receptor antagonists.

But the greatest enthusiasm is reserved for the development of new class III antiarrhythmic agents. Azimilide is the one believed closest to the marketplace; marketing approval in the United States and Europe may be only a few months away, according to Dr. Le Heuzey, professor of medicine at Marie Curie University Paris.

Double-blind randomized clinical trials involving nearly 1,400 patients indicate that azimilide can be started safely on an outpatient basis. The incidence of torsades de pointes with this drug is low.

Another promising class III drug for chronic AF is dronedarone, a structurally close derivative of amiodarone, widely considered to be the most effective available rhythm control agent. In addition to its class III effects, dronedarone also possesses class I, II, and IV antiarrhythmic actions. Unlike amiodarone, dronedarone contains no iodine and so appears to be free of the adverse thyroid effects common with the parent drug, said Dr. Bramah N. Singh, professor of medicine at the University of California, Los Angeles.

To date, pulmonary fibrosis--a problematic complication of amiodarone--has not been seen with dronedarone, he added.

Dr. Paul Dorian of the University of Toronto has been involved in studies of tedisamil, another class III drug. Tedisamil is a nonselective potassium channel blocker with relative atrial selectivity Although data from just-completed randomized trials of intravenous tedisamil for acute AF are still being analyzed, there is reason for optimism that this drug causes less QT prolongation and has less possibility of potentially fatal torsades de pointes than current antiarrhythmics.

Dr. Stefan H. Hohnloser predicted continued growth of drug development activity for AF.

"The efficacy of the new agents, as far as I am concerned, is probably comparable to that of traditional agents used for the same purpose. So I think there is a continued need for the development of new, more effective antiarrhythmic drugs," said Dr. Hohnloser, professor of medicine at J.W. Goethe, Frankfurt, Germany.
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Comment:New Rhythm control drugs slated for Atrial Fib. (Azimilide May Get Marketing Approval Soon).
Author:Jancin, Bruce
Publication:Family Practice News
Date:Jan 1, 2003
Words:544
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