Simultaneous with Dr. Connolly’s presentation at the AHA meeting, the PALLAS results were published (N. Engl. J. Med. 2011 Nov. 14 [doi:10.1056/NEJMoa1109867]).
"It’s clear ... that dronedarone should not be used in patients with permanent AF who have a high burden of vascular disease."
In an accompanying editorial, Dr. Stanley Nattel of the Montreal Heart Institute referred to dronedarone in AF as a "Jekyll and Hyde" drug (N. Engl. J. Med. 2011 Nov. 14 [doi:10.1056/NEJMe1111997]). He said that exactly why dronedarone was so harmful in PALLAS and yet so beneficial in ATHENA may never be known for certain. Was the key factor in PALLAS the permanent AF, the high burden of vascular disease overall, the substantial prevalence of heart failure, or something else? Regardless, the PALLAS experience warrants a revised, far more limited role for dronedarone moving forward, according to Dr. Nattel.
Not only should dronedarone absolutely be avoided in patients with permanent AF, it should also be avoided in high-risk patients with intermittent AF, particularly if they have heart failure. If dronedarone is to be prescribed in patients on digoxin, dose adjustment of the digoxin is now clearly mandatory, he continued.
And the major guidelines for management of AF need to be reexamined. Since receiving marketing approval, dronedarone has figured prominently in the treatment algorithms for patients with paroxysmal or persistent AF. Now, however, it seems appropriate to reserve the antiarrhythmic for selected low-risk patients, and perhaps only those in whom other antiarrhythmic drugs have failed, Dr. Nattel said.
Dr. Estes disagreed. The latest AHA/American College of Cardiology guidelines characterize dronedarone as a reasonable drug for maintaining sinus rhythm in patients with recurrent paroxysmal or persistent AF who have no structural heart disease, or who have hypertension without left ventricular hypertrophy, or in those with CAD without heart failure (Circulation 2011;123:104-23).
"I think that these guidelines still apply," he said.
Dr. Connolly disclosed having received research grants and honoraria from Sanofi-Aventis, which sponsored PALLAS. Dr. Estes and Dr. Nattel reported no relevant financial interests.