Dronedarone debut: will it be successful?

In the wake of dronedarone’s successful but controversial advisory panel meeting in March, a perspective in the New England Journal of Medicine by Peter Zimetbaum reviews the complicated history of the drug and makes a cautious forecast that the drug may be accepted into clinical practice when and if it gains FDA approval:

“So where does dronedarone fit into the antiarrhythmic armamentarium? In terms of efficacy, it does not represent a step forward. In terms of safety, in a population without decompensated heart failure, it confers no apparent risk of ventricular tachyarrhythmia, and there is no obvious evidence of clinically significant, chronic toxic effects. Clinicians and patients will have to determine whether safety is enough to drive the use of a new antiarrhythmic drug; I, for one, suspect it will be.”

CardioBrief asked advisory panel members Darren McGuire and Sanjay Kaul to comment.

Kaul thought that Zimetbaum presented “a fairly balanced perspective on dronedarone” but both Kaul and McGuire felt he did not sufficiently appreciate the lack of evidence supporting a superior safety claim for dronedarone over amiodarone.

McGuire also noted that, contrary to Zimetbaum’s assertion, the panel did not vote on an indication of atrial fibrillation suppression. According to McGuire, “the proposed indication was for the reduction of cardiovascular hospitalization or death, and the committee voted to approve an indication for the prevention of cardiovascular hospitalization driven by atrial fibrillation/flutter”

Responding to the criticism, Zimetbaum told CardioBrief that the purpsose of the perspective was “to offer an internal medicine audience a view of this new drug. I think the issue for the average practioner to understand is that although this is not a blockbuster drug in regard to efficacy it has been vetted reasonably well and at least for the duration of 21 months of follow up (ie, in an Athena population) looks quite safe.”

Kaul was somewhat less enthusiastic in his clinical recommendation:

“…the key questions are why and when to use it in clinical practice. Perhaps the default treatment choice should be low-dose amiodarone… with the option to switch to dronedarone only in case of significant side effects. I would avoid the use of dronedarone in patients with heart failure or impaired left ventricular systolic function because I am not convinced that its safety has been established in these patients. Finally, from a clinician’s perspective, efficacy trumps safety. Why would anyone prescribe a therapy that barely works, but promises to be safe?”

Zimetbaum disagreed with Kaul: “Efficacy does not trump safety!!” he wrote. “I think it is unlikely that doctors will choose a drug like amiodarone with proven lethal side effects over a drug like dronedarone, which though likely less effective, is undoubtedly much safer.”

Click here to watch  C. Michael Gibson’s video interview with Zimetbaum.


  1. Roger Alvarez says

    One of my concerns is Dr. Zimetbaum’s stated conflict of interest in receiving consulting fees from Sanofi-Aventis. I thought that his editorial was mostly measured, with the exception of the last time. However, his comments in the message and video seem much more favorable. He makes an argument for safety, which does not seem to be sufficiently backed. Essentially, 1 positive safety study and 1 negative safety study. Seems that there will likely be less thyroid toxicity, which is nice, but patients with a-fib are more likely to die from heart failure than thyroid toxicity or pulmonary fibrosis. Given the AFFIRM trial, it doesn’t even seem clear that NSR should be the goal.

    I like the idea of a safer amio, but given the decreased efficacy or dronedarone compared to amio, it doesn’t seem like that’s what we really have… yet.

    He also speculates that the results of AFFIRM would be different with today’s drugs. Well, that’s nice, and a reasonable hypothesis, but reasonable hypothesis does not evidence-based medicine make.

  2. Roger Alvarez says

    I was still listening the video when I made that comment. I remain concerned with his tone throughout the video. It seems like he recommends Dronedarone over Amiodarone. Since Dronedarone isn’t even approved, that doesn’t quite seem reasonable. NEJM could have found an commentator without the COI. Why didn’t they?

  3. A classic case of enthusiasm exceeding the evidence!

  4. vernchichak says

    as with most “new” drugs entering the market there is always a large hype then 6 monrhs down the road the correct posturing of where a drug will and should be used is further defined,frankly at the end of the day efficscy I believe will win out prephaps there should be a trial of dronederone and abation therapy(ie, pulmoanary vein abation

  5. amiodarone made me ill the first two weeks and just when I was a day away from taking the lower dose I broke out in hives. I’m aprehensive but I’m going to try multaq because I’m going into afib too often . I’ll keep you posted

  6. Does this drug also help with PVCS? How save is this drug with pts with CHF and cardiomyopathy, and sick sinus syndrone and has a pacepaker-ICD? Thanks Nancy

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